#532: Updates in Fibromyalgia Management featuring Dr. Dan Clauw

Summary

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Podcast Summary: The Curbsiders #532 – Updates in Fibromyalgia Management ft. Dr. Dan Clauw (July 13, 2026)

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Episode Overview

In this episode, The Curbsiders welcome back Dr. Dan Clauw, a leading expert in chronic pain from the University of Michigan, to dive into the latest updates in fibromyalgia diagnosis and management. The conversation covers evolving diagnostic criteria, advances in understanding the neurobiology of fibromyalgia, evidence-based nonpharmacologic and pharmacologic treatments, and practical advice for discussing care with patients.

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Key Discussion Points & Clinical Insights

1. Modernizing Fibromyalgia Diagnosis

• Adequate Workup: Before diagnosing fibromyalgia, ensure sufficient evaluation to rule out mimics (e.g., hypothyroidism, early autoimmune disease) with basic labs: ESR, CRP, TSH, metabolic panel, CBC, and consider the patient’s history. (08:22-09:48)
  • "She’s had at least the workup that she needs, if not a little bit more than she needs... everyone before they get diagnosed with fibromyalgia should have a sedimentation rate, a C-reactive protein, a TSH, metabolic panel…" – Dr. Clauw (08:22)
• Evolving Diagnostic Criteria: Move away from “tender point” exams (deemed “stupid” by Dr. Clauw) and towards using tools like the Widespread Pain Index (WPI), Symptom Severity Scale, or fibromyalgia questionnaires with a pain body map. (28:03-31:41)
  • "Thank you for saying tender points are no longer in vogue. I would say they're stupid and stop doing them..." – Dr. Clauw (28:03)
• Gender Disparities: 1990 criteria biased diagnoses towards women due to gender differences in pain sensitivity. Modern criteria recognize fibromyalgia in men at much higher rates. (28:11-29:22)
• History Hallmarks: Most fibromyalgia patients had prior “chronic overlapping pain conditions” (COPCs, e.g., migraines, IBS, pelvic pain) before widespread pain emerged. (10:09-11:09)
• Nociplastic Pain: Updated terminology for central sensitization/cerebral amplification — not a diagnosis, but a descriptive mechanism underlying conditions like fibromyalgia. (11:09-11:42)

2. Neurobiology & Etiology

• Sensory Sensitivities: Ask about sensory hyperresponsiveness (e.g., sensitivity to light, noise, odors – “exteroception”; internal cues like palpitations, nausea – “interoception”). Multiple sensitivities are highly predictive of nociplastic pain. (13:50-15:45)
  • "When you have multiple sensory sensitivities, that really only can be a brain or a central nervous system problem." – Dr. Clauw (14:42)
• Brain Imaging & Genetics: Functional MRI reveals hyperconnected brain networks in fibromyalgia patients. New studies show similar patterns pre-symptom onset in at-risk children; recent GWAS implicate CNS-focused, polygenic risk. (20:51-23:58)
  • "We saw in the kids while they were still symptom free ... their brains looked about 2/3 like adults with fibromyalgia." – Dr. Clauw (22:22)

3. Doctor-Patient Communication

• Patient Education Approach: Do not talk down to well-informed patients. Acknowledge varied belief systems about the illness, and gently use education and listening to guide understanding. (24:05-26:40)
  • "I just listen to patients ... if you listen really carefully to patients, they tell you a lot." – Dr. Clauw (26:01)

4. Nonpharmacologic Management: The Foundation

• Key Pillars: Activity (not “exercise”) and sleep are paramount. Emphasize gradual graded activity, as too rapid an increase can exacerbate symptoms. (43:07-44:54)

  • "Use the word activity because actually that's— usually people with fibromyalgia have become fairly sedentary, and your first phase is getting them moving before you're really getting them to do anything that we would really call exercise." – Dr. Clauw (43:07)

• Evidence-Based Integrative Therapies: Strong evidence now for yoga, tai chi, acupuncture, mindfulness, myofascial release, and chiropractic manipulation. Encourage patients to try 3 nonpharm modalities; most find 1 that meaningfully helps. (41:26-42:35; 52:10-53:44)

• Tailored Physical Therapy: Not all PTs are effective; prefer those skilled in pain reprocessing and chronic pain. “No pain, no gain” approaches can worsen patients. (46:01-48:53)

  • "Some physical therapists, especially ones that are trained to do like sports medicine… probably routinely make these people worse… know your local resources..." – Dr. Clauw (46:01)

• Patient Education Resources:

  • painguide.com: Free, evidence-based resource with videos, modules on sleep, and self-administered modalities.
    • “It’s got a treasure trove… for a provider, if you really want to work with patients and say let’s work this time on sleep, go to this website, read all that whole chapter…” – Dr. Clauw (49:48)
  • Chronic Pain Reset by Afton Hassett, PhD: An accessible evidential book for patients (82:25-82:45).

5. Pharmacologic Management

• Principles:

  • Medications can help, but average benefit is modest (1–2 points on a 0–10 pain scale); nonpharmacologic therapies often provide superior results. (41:13)
  • Choose medications matching the most bothersome symptoms (e.g., target sleep, mood).

• First-Line Medications:

  • Sublingual Cyclobenzaprine (newest FDA-approved) – low dose, well tolerated, improves sleep.
  • Duloxetine – SNRIs preferred over milnacipran for tolerability.
  • Gabapentinoids (gabapentin or pregabalin) – considered roughly equivalent.
  • Other TCAs (e.g., amitriptyline, nortriptyline) can be used, but cyclobenzaprine is best tolerated.
  • "If you give the tablet, you can give a 5 mg tablet. The sublingual form is 2.8 mg... At the end, they're taking a little bit more than 5 mg of cyclobenzaprine." (57:31)

• Targeting Sleep: Improvement in sleep often precedes pain benefits. Polysomnography shows these drugs increase restorative deep sleep. Insomnia is a strong risk factor for fibromyalgia development. (59:31-61:09)

  • "The preferred hypnotics if you’re trying to get people with fibromyalgia to sleep better—cyclobenzaprine would be my first choice and pregabalin or gabapentin ... second choice." – Dr. Clauw (58:44)

• Other Drugs:

  • Milnacipran – less tolerated.
  • Low-dose naltrexone – help in ~1/3 of patients, though evidence is mixed. (67:08)
  • "It certainly seems to be well tolerated and safe. And so I think it's well worth trying." – Dr. Clauw (67:27)

6. What Not to Use: Opioids and Cautions

• Opioids: Strongly discouraged for chronic fibromyalgia. No high-quality evidence of benefit; concern for worsening pain due to opioid-induced hyperalgesia and increased all-cause mortality. (62:21-65:57)
  • "Pure mu opioids... often will make people worse … if you have to use an opioid in people with fibromyalgia, buprenorphine would be by far the best… don't use a pure mu opioid, an oxycodone or hydrocodone derivative…" (62:21-66:34)
• Tramadol: Its dual effect (SNRI + opioid) may explain subjective benefit, but use with caution.
• Opioid Tapering Strategies:
  • Never force abrupt tapers (“we’re playing chess, not checkers”).
  • Use evidence/factoids: long-term opioids double all-cause mortality, at least 50% of patients improve or feel no worse with taper.
  • Taper gradually; allow reversal if needed.
  • "I’m not taking them away, I’m just asking you to be sure that they're helping you enough that you should keep taking them." – Dr. Clauw (72:11)

7. Cannabinoids for Fibromyalgia

• Current Evidence & Guidance:

  • Research ongoing; low-dose oral THC may help, but most users overshoot therapeutic doses and route.
  • Avoid inhalation; oral administration preferred.
  • High doses risk suppressing endogenous cannabinoid systems (potentially causing hyperemesis).
  • CBD alone is very safe; efficacy still uncertain.
  • "A low amount of THC works better for pain than a high amount... I'm holding out hope that CBD alone might be helpful for certain types of pain because it's super safe." – Dr. Clauw (77:01)

• Therapeutic Coaching: MI-funded trials are being conducted to guide patients on dosing and administration to optimize benefit and minimize harm. (75:59-78:18)

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Notable Quotes & Memorable Moments

• “Fibromyalgia and nociplastic pain are very real. We are beginning to understand the neurobiology of these conditions better and better.”
  (80:12 – Dr. Clauw)

• “If you see an individual that has more than one [chronic overlapping pain condition], it's likely that their pain is coming more so from the brain, central nervous system, central sensitization.”
  (12:33 – Dr. Clauw)

• “Nonpharmacologic therapies—there’s certainly far more nonpharmacologic therapies that work in fibromyalgia or that work in pain than there are drugs…”
  (41:26 – Dr. Clauw)

• “If you try it and your pain gets worse, then you go right back up to the same...I’m not taking them away, I’m just asking you to be sure that they’re helping you enough that you should keep taking them.”
  (72:11 – Dr. Clauw, on opioid tapering)

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Timestamps: Important Segments

• [08:22] – Reasonable workup and mimics to consider before diagnosing fibromyalgia
• [11:09-11:42] – The shift to "nociplastic pain" terminology and mechanism
• [13:50-15:45] – Assessing sensory hypersensitivity; exteroception/interoception overview
• [20:51-23:58] – Brain imaging, genetics, and heritability
• [28:03-31:41] – Abandoning tender point exam; gender bias in old criteria; use of questionnaires/body map
• [41:13-44:54] – Medications provide modest relief; focus on activity and sleep as basics; language tips for patient buy-in
• [46:01-48:53] – Pitfalls of standard PT; finding the right therapists for fibromyalgia
• [49:48-51:21] – Patient educational resources: painguide.com, Chronic Pain Reset
• [52:10-53:44] – Pick 3 nonpharmacologic therapies; expect 1 to “stick”
• [57:31] – Practical dosing for sublingual cyclobenzaprine
• [59:31-61:09] – Sleep improvement leads pain improvement; sleep disruption as predisposing factor
• [62:21-66:34] – Opioids in fibromyalgia: strong evidence against, strategies for deprescribing
• [67:08] – Low-dose naltrexone: practical summary
• [72:11] – Patient-centered approach for opioid taper
• [75:04-78:18] – Cannabinoids: current research, oral route preferred, low dose, CBD outlook
• [80:12-82:03] – Dr. Clauw’s clinical takeaways & early/intervention priorities

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Take-Home Points (Dr. Clauw’s Summary)

1. Fibromyalgia and nociplastic pain are very real conditions with advancing neurobiological understanding.
2. Early diagnosis and intervention are critical. The sooner identified—ideally when patients present with their second chronic overlapping pain condition in adolescence or early adulthood—the better the prognosis.
3. Nonpharmacologic treatments (activity, sleep, integrative therapies) are the foundation; medications may help but have modest effects.
4. Avoid opioids and unnecessary polypharmacy.
5. Empower patients with education, shared decision-making, and credible resources (painguide.com, “Chronic Pain Reset”).

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Additional Resources Mentioned

• painguide.com
• Book: Chronic Pain Reset by Dr. Afton Hassett

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(Summary by The Curbsiders Internal Medicine Podcast Team)

Transcript

[Podcast Host (Ad Reader)]

Hey, before we get to the show, I wanted to remind you to check out our [e-mail] curbsiders. If you haven't signed up yet, sign up now to get ad free episodes, twice monthly, bonus episodes, and a whole bunch of other cool [e-mail] curbsiders

[Dr. Matthew Frank Watto]

Zoe, you have a pun for Paul? Maybe two.

[Dr. Paul Nelson Williams]

I have one.

[Zoya Surani]

It's not very good though. But Paul, why did the skeleton go to the party alone?

[Dr. Paul Nelson Williams]

God, I, I'm, I'm like stuck on a byob bring your own bones thing. That can't be right. So, yeah, I, I, I, I don't know. So, yeah. Why, why did he go to the party alone?

[Zoya Surani]

He had no body to go with.

[Dr. Paul Nelson Williams]

Oh, I should have gotten there. Now I'm disappointed in myself.

[Dr. Matthew Frank Watto]

Paul, another bad one for you. I told my back to stop acting up. You know why?

[Dr. Paul Nelson Williams]

No.

[Dr. Matthew Frank Watto]

You know why? He didn't listen to me. No, Matt, tell me he had too much spine.

[Dr. Paul Nelson Williams]

Yeah, I never would have gotten there. All right, all right.

[Dr. Matthew Frank Watto]

That was mortifying.

[Podcast Disclaimer Voice]

The Curbsiders podcast is for entertainment, education and information purposes only, and the topics discussed should not be used solely to diagnose, treat, cure or prevent any diseases or conditions. Furthermore, the views and statements expressed on this podcast are solely those of the host and should not be interpreted to reflect official policy or position of any entity aside from falsely cash like more homophobic and affiliate outre programs, if indeed there are any. In fact, there are none. Pretty much. We aren't responsible if you screw up. You should always do your own homework and let us know when we're working.

[Dr. Matthew Frank Watto]

Welcome back to the curbsiders. I'm Dr. Matthew Frank Watto, here with my great friend and America's primary care physician, maybe even the primary care physician, Dr. Paul Nelson Williams.

[Podcast Host (Ad Reader)]

Hey, Paul.

[Dr. Paul Nelson Williams]

Hey, Matt. How are you?

[Dr. Matthew Frank Watto]

I'm doing well. We have a returning guest, Dr. Daniel Kwa. Thank you. Talking about fibromyalgia. But Paul, before we introduce him and our co host, what is it that we like to do on the Curbsiders?

[Dr. Paul Nelson Williams]

Sure. Or to put it another way, what we do on the Curbsiders is that we are the internal medicine podcast. We use expert interviews to bring your clinical pearls and practice changing knowledge as you alluded to. We are joined by a co host and producer for this episode, med student and one of my many future bosses, Zoya Sirani. Zoya, how are you?

[Zoya Surani]

I'm doing great. Thanks for having me here.

[Dr. Paul Nelson Williams]

We are delighted to have you. Why don't we have you tell us about who we talk to and maybe even a little bit about what we talked about.

[Zoya Surani]

Of course. So we have a fantastic conversation coming up with our guest, Dr. Dan Klaw, who actually joined us back in 2016 for a two part fibromyalgia and Chronic Pain Management episode series. Dan Claw is a professor of anesthesiology, medicine, rheumatology and Psychiatry at the University of Michigan. He serves as director of the Chronic Pain and Fatigue Research center and co Director of the HEAL National K12 Clinical Pain Career Development Program. He's become an internationally known expert in chronic pain and we are so glad he is here to rejoin us to teach us about updates in fibromyalgia diagnosis and newer treatment options. So without further ado, let's get to it.

[Dr. Matthew Frank Watto]

A reminder that this and most episodes will be available for CME credit for all health professionals through VCU healtherbsiders.vcuhealth.org Dr. Claw has done consulting for multiple companies and received research support from multiple companies which we list in our show notes. However, the discussion on this episode was fair and balanced and we avoided trade names when possible. Well, Dan, thank you so much for coming on the show. Really excited to talk to you again. It's been a long time since we talked. So the audience wants to know what are you currently enjoying as like a hobby or interest outside of what you do in medicine?

[Dr. Daniel Clauw]

I have a lot of hobbies. I really enjoy playing tennis. We live on a lake and I love taking kids tubing. But probably the thing that I enjoy the most is cooking and I think it actually helps science a lot. I cook a lot and bring in food for 30 or 40 people in our research group. And I learned that from my grandmother, my Italian grandmother is food's a great way to bring people together and to bring and to socialize. And it's been really effective for team science to promote team science.

[Dr. Matthew Frank Watto]

Yeah, I don't think anybody will object to you bringing in food, especially if you're a good cook. So are you making Italian for the team?

[Dr. Daniel Clauw]

I'm everything and I joke with them is that you're lucky that I don't knit because then you'd have too many beanies.

Yeah.

As cooking everyone really enjoys good food, so it's not a bad hobby for the rest of the people around you.

[Dr. Paul Nelson Williams]

There's a running joke at one of the clinics where I work that if I brought in a bait good for that week, that means I did something catastrophically bad the week prior. And that's actually not completely Inaccurate, unfortunately.

[Dr. Matthew Frank Watto]

Paul, did you want to know anything else before we get to the case?

[Dr. Paul Nelson Williams]

Sure, we'll do the usual. Dan, is there any advice or feedback that you like to consistently give your learners that you have found especially helpful in your own life?

[Dr. Daniel Clauw]

Well, again, I mentor a lot of individuals, and I think one of the things that I really encourage them to do is to reach out to a lot of different people to help mentor. We do team mentoring, like, we do team science, and I think a lot of people often feel, like, intimidated about reaching out to someone like myself. It's like, oh, he's important. He won't answer my email. He won't agree to mentor me. And I mentor pretty much anyone that asked me to mentor them because I just find it so enjoyable myself. And certainly at this point in my career, it's a way of sort of paying forward.

[Dr. Matthew Frank Watto]

Yes. It seems like looking on the website, through your bio and everything, it seems like it's been just like a cascade effect. I have a family member who. She's like the matriarch on my wife's side, and she's had so many grandchildren that just. It spreads out. And I imagine if you're at the top of, like, a giant pyramid of research, you have all these PhDs and then they have PhDs, and so you're kind of. Yeah. It must be really cool to see that after. After all the research you've done.

[Dr. Daniel Clauw]

Yeah. And I. And I'm in the grandchild phase in my research career.

We don't have any grandchildren yet. We're still waiting for one or the

other of our sons to produce grandchildren.

But I have a lot of scientific grandchildren, second or even third generation of people that I originally mentored, that I

still help mentor their mentees.

[Dr. Matthew Frank Watto]

Paul, we're getting into that in podcasting now, too. So we know on a very, very small scale what that's like to have people that we worked with that are now, like, doing their own podcasts and, And. And doing great work, too. So it's.

[Dr. Daniel Clauw]

It.

[Dr. Matthew Frank Watto]

I can say on a very small level, I know what that's like to see.

[Dr. Paul Nelson Williams]

I just came back from one of the national conferences, so the ESHAM Conference and ran to someone who's like, oh, I was one of your medical students. I'm like, oh, that's so nice. Yeah, I've been an attending physician for six years now. I'm like, that can't be right. That math doesn't check out. So, yeah, time. It's bad.

[Dr. Matthew Frank Watto]

But you know what else is bad, Paul? Chronic pain. And I think we should get to a case because we want to teach the audience how we can do a better job at this because I think in general there's a lot to be desired about how we approach this. Zoya, would you read our first case?

[Zoya Surani]

Yeah, of course. Thanks for that incredible transition in so our first case is a 42 year old female presents to her primary care clinic as a new patient. She has been seen by three prior physicians over two years for diffuse body pain, fatigue, poor sleep and brain fog. Her chart has a negative ana, negative rf, normal esr, crp, normal tsh, cbc, cmp, ck, vitamin D, level Lyme serologies, and a normal MRI of the thoracic and lumbar spine. She shares that she has been previously told all of your tests are normal and feels confused and dismissed in her symptoms and pain. She asks you, can you help me? Do I need to see a rheumatologist? So first question, based on our patient's case, when you have a patient present to your clinic with these symptoms in this workup, what are the first things going through your mind?

[Dr. Daniel Clauw]

The first things really are, has this

individual had an adequate workup to rule out alternative causes of the symptoms that she's experiencing?

And I think she's had at least the workup that she needs, if not

a little bit more perhaps than she

needs all the imaging and was probably

unnecessary given the diffuse nature of the pain. But I think that everyone before they

get diagnosed with fibromyalgia should have a sedimentation rate, a C reactor protein, a TSH metabolic panel, because there are a fair number of conditions that can sort of mimic fibromyalgia. Especially early autoimmune diseases can sometimes look

a lot like fibromyalgia.

[Zoya Surani]

So kind of on that line of thought, what would be a differential diagnosis for her and if she hadn't had workup yet?

[Dr. Daniel Clauw]

Well, again, if she hadn't had a workup yet, then you'd think about things

like hypothyroidism, really early autoimmune disease.

But given that she's had symptoms for

several years, that's not likely.

Individuals typically, if they have an autoimmune disease, it'll really express itself pretty fully

in the first six to 12 months.

So when I say early, I really mean early autoimmune disease. So I think that this individual, especially again after she had these types of

symptoms for two to three years, just

some really modest testing, would be fine to really rule out anything other than fibromyalgia.

It's also Very helpful to get a history that someone like this almost invariably had several regional pain syndromes earlier in their life before they had widespread pain.

And so that's helpful to get that in the history.

It would make you more comfortable if

this is an individual that, for example,

had growing pains or painful menstrual periods

or headaches or things like that as an adolescent or as a young adult. Because you almost always will see that these individuals who end up having widespread pain at age 30, 35, started out by having a series of different regional

or now what we're calling chronic overlapping

pain conditions, conditions like headache, irritable bowel, fibromyalgia, interstitial cystitis, bladder pain syndrome, vulvodynia.

All of those conditions really are sort of regional forms, if you will, of

what we now call nociplastic pain or the kind of pain that we see in fibromyalgia.

But typically, people will have one or

more of those regional pain syndromes earlier in life before their pain becomes so widespread that we would say that's fibromyalgia.

[Dr. Matthew Frank Watto]

And nociplastic pain is a newer term. I think maybe even last time we spoke with you, we were saying central sensitization. Can you talk a little bit about the terminology you just mentioned, what chronic overlapping pain syndromes are? I think the audience will be able to get those, because in primary care, we're so used to hearing and coming across those. But what about this nociplastic pain?

[Dr. Daniel Clauw]

Yeah, nociplastic pain is the new term that's really replacing central sensitization.

And it's not a diagnosis.

It's more of a mechanistic description of

the type of pain that people have.

[Dr. Matthew Frank Watto]

Speaking of somatic, somatosensory things or somatosensory symptoms, I heard in one of your talks that, and you just kind of mentioned it, alluded to it, that young people that have one or more of these somatosensory complaints, whether it's the bladder or temporomandibular disorder or headaches, that they're people that are at high risk going down the line for developing, like, a widespread pain like fibromyalgia. And that's something that I hadn't really heard before. And you also told us, and I want to kind of bring us into this, that you're sometimes able to predict some other symptoms people might have. So can you talk about the interoception, extroception and how you might pull, like, a patient like this? You might ask them some of those questions. I imagine if you're seeing them, sure.

[Dr. Daniel Clauw]

So first, I'll talk a little bit

more about chronic overlapping pain conditions, because I think there's a really key point here.

The term chronic overlapping pain conditions means

that if you see an individual that

has more than one of these, it's

likely that their pain is coming more

so from the brain, central nervous system, central sensitization.

So one of the chronic overlapping pain

conditions, for example, is low back pain.

And we know that a lot of

individuals have low back pain because of neuropathic pain or even nociceptive pain.

But if someone has low back pain

plus headache plus irritable bowel, it's much more likely their low back pain is an osoplastic central sensitization than neuropathic or.

And so it's when you have several

of those conditions that that will cue you into the fact that this individual

is likely has a CNS problem that's driving them to have pain virtually in

any region of the body. And these labels are often just sort

of connotations for pain in the pelvis,

pain in the abdomen, pain in the

head, that they're the labels that have historically been used for people that had

pain in those regions of the body

but didn't have underlying peripheral pathology.

[Podcast Host (Ad Reader)]

I see.

[Dr. Daniel Clauw]

And then the second set of questions

you asked about interoception and exteroception, this is in the last five or so years, I think, become increasingly recognized as being important in conditions like fibromyalgia and in central sensitization. And that is that these individuals are not just more sensitive to painful sensory stimuli. They're more sensitive to external sensory stimuli like lights, noises, odors.

And so it's just simply asking someone, yes, no. Are you bothered by bright lights? Are you bothered by loud noises? Are you bothered by odors?

Can give you a good clue.

Again, if someone is sensitive to more

than one of those, they almost certainly

have nociplastic pain, central sensitization.

There are some people that are just

bothered by lights or just bothered by noises and odors. But when you have multiple sensory sensitivities,

that really only can be a brain or a central nervous system problem.

So the external sensory sensitivity is called exteroception.

And then internal sensory sensitivity are how you feel symptoms like nausea, palpitations, stiffness, dry eyes.

And so there's a lot of other symptoms that are occurring from sort of

within the body that are called enteroception.

And the interesting thing is that the

enteroceptive and extreptive sensory systems are the afferent component of the autonomic nervous system.

And so we see that these individuals

with conditions like fibromyalgia have a lot of autonomic dysfunction and it makes sense

because they have afferent hypersensitivity of these sensory systems and that similarly then affects they often end up with low parasympathetic

tone, low vagal tone, high sympathetic tone,

and that that imbalance causes a lot of the symptoms that we see in these conditions.

[Dr. Matthew Frank Watto]

Yeah, it's just fascinating.

[Podcast Host (Ad Reader)]

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[Dr. Matthew Frank Watto]

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[Podcast Host (Ad Reader)]

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[Dr. Paul Nelson Williams]

Along those lines we're going to talk a lot about pain in this episode, and I feel like that is often the primary focus for someone who presents like this. So in addition to the somatic components, what kind of questions do you ask in terms of things like the fatigue and the poor sleep and the brain fog? Are those things that you ask about specifically? Do patients tend to volunteer those? Like what about the other sort of associated symptoms that we often see in cases like this?

[Dr. Daniel Clauw]

I think like most providers, I'll first have the person give a chief complaint

and tell what they are most bothered by and then I'll go in and

sort of fill in the blank.

So if they the somatic symptoms that commonly co occur with this kind of

pain are fatigue, sleep problems and memory problems.

And so if they don't volunteer that

they have those symptoms or don't have

those symptoms, I'll explicitly ask about those symptoms.

Then I will ask about some symptoms

of both internal and external sensory hyper responsiveness. And those are really helpful sometimes to convince the like later even maybe not

as part of the classic history and

physical, but a little bit later when you're talking to the person and trying

to explain nociplastic pain to them and you say you know, the reason that you find a light to be bright, a noise to be loud, and you

have pain is that there's certain brain regions that code for the intensity of all sensory stimuli.

And if you have an increase in

this sort of amplifier in your central nervous system for sensory processing, that's why

you have all of these different symptoms

that may at face feel like they're

disparate like that they couldn't have any sort of physiologic tie to each other because really many symptoms are part of

this sort of anteroceptive exteroceptive set of symptoms.

[Dr. Matthew Frank Watto]

Do we know yet? It sounds like we have some. Well, do we know the etiology, like what's driving this? It sounds like we can measure Abnormalities in the central nervous system with functional imaging and things like that. But how do we. Do we have any idea yet what's causing this?

[Dr. Daniel Clauw]

Yes, certainly on functional imaging you see that there's brain networks that are not normally very connected to each other, that

are too connected to each other in these individuals.

And it's the kind of networks that you would sort of expect.

The salience network, the somatosensory networks are sort of hyperconnected to other networks like the default mode network that normally is a network that is when you're resting, it's mainly active when you're resting.

And so you see this hyperconnectedness.

And one of the coolest studies that we've ever done in our group, at least in my estimation it's one of

the coolest studies is a study that

Chelsea Kaplan led and it showed that in a big study that's still ongoing

in the United states called the ABCD

study, it takes kids that are healthy

at age 9 and follows them longitudinally

until they're age 18. And it does functional brain imaging every

two years and asked them a whole

bunch of questions over this nine year period.

We published a study that showed in

the kids who got functional brain imaging at age 9, when they entered that

study and they had no pain, they had to be healthy to enter the study. The kids that at age 10 had new multi site pain, had pain in

more than one location were the cases. The controls were all the kids who

didn't develop new pain between age 9 and age 10. And when we went back and looked

at those 9 year olds that developed pain one year later, their brains looked about 2/3 like adults with fibromyalgia.

All the brain imaging abnormalities we see in adults with established fibromyalgia we saw

in the kids while they were still symptom free, they were about in the next year they were gonna start to develop symptoms. But we think we're really imaging this sort of predisposition and the fact that these neural networks are sort of hypermeshed

and that this is an individual that's at risk of going on to develop

nociplastic pain, central sensitization.

[Dr. Matthew Frank Watto]

And we haven't found like a genetic gene or traumatic brain injury or virus or something like that pushes people towards this.

[Dr. Daniel Clauw]

We were just involved in a big

study that just got published that looked at genome wide association findings in almost

4 million individuals in fibromyalgia.

And it did come up with 12

or 13 genes, almost all of which are in the central nervous system.

It sort of confirmed that this is a central nervous system disease that was

just published in Nature Medicine.

We're starting to think about interrogating some of those specific genes.

But that's about where we are right now, is we're sort of getting early

gwas and genetic findings.

The thing about fibromyalgia that we know

is it's very familial.

If someone has fibromyalgia or one of

these other chronic overlapping pain conditions, their children are more likely to develop these conditions as well.

But it's not any single gene.

Like a lot of other complex medical illnesses, it's polygenic.

And we're starting to learn the set

of genes that might be involved in conferring this risk.

[Zoya Surani]

I had a question kind of related to how into the etiology and everything we're going. Do you explain this level of depth and detail with patients, or what does your normal spiel look like when talking to them about fibromyalgia?

[Dr. Daniel Clauw]

I don't start here, but many people with fibromyalgia or something akin to fibromyalgia

are extremely well read and well educated.

So I also am not silly enough

to talk down to patients. So I'll start at sort of like

a neutral, you know, usual the way

a physician will talk to someone. But I often I'm pretty down in

the weeds because they've read all these articles.

And another thing that happens which isn't

as much of a problem for me as it would be if you're a primary care physician.

If someone's seeing me, it's like, oh, this Dr. Claude knows what he's talking about.

But if you're a primary care physician,

you might get challenged a lot by these patients that I think it's this or I think it's this. And certainly I wake up every day

to one or two emails from someone in the world that now knows the cause of fibromyalgia.

And, you know, because of their own

anecdotal personal experience and you have to

take people where they are. If they.

If they have, you know, this sort of belief system about this, that or something else that is causing their fibromyalgia, I just think it's my responsibility.

I don't immediately try to dissuade them

of their current beliefs.

I just try to educate them about what we know now about fibromyalgia and nociplastic pain and sort of bring them along gradually and slowly because no one likes being told, you don't know what you're talking about, or I'm the doctor

and I'm the smarter one.

And so I'm not. And frankly, I just said this to several people where they've talked about, like,

oh, you made all these contributions to science.

And it's like, I just listen to patients. You know, I think if you listen really carefully to patients, they tell you a lot. And so I think I have historically been a good listener, and I've moved a lot of the things that I heard from patients into a research setting. And I think that that's important when you're interacting with these individuals, because they are going to come in with all sorts of different belief systems, and it's not their fault that they got down that rabbit hole or another rabbit hole. And so I think we have to be sort of gentle in extracting them from some of these rabbit holes.

[Dr. Matthew Frank Watto]

So I want to recap what we talked about before I ask the next question. We said that fibromyalgia is often preceded by other pain syndromes. Could be. Could be headaches, could be temporomandibular, but various other body systems. And then over time, people tend to develop widespread pain, and they often will also complain of fatigue, sleep disturbances, cognitive or memory difficulties. And you mentioned that for the basic workup, they probably don't need a ton of labs, but you want to make sure you're looking for some other things. So thyroid, a sedimentation rate, comprehensive metabolic panel. I think you said a CBC as well. So it's a pretty basic workup. It's a lot of history asking about sensitivity to lights and noises and smells. That's extroception or internal signals, interoception. So that could be like palpitations or dry eyes. Things other than pain that they're very sensitive to. But how are we putting this together to make a diagnosis of fibromyalgia? Should we be using the 2010, 2011 criteria? I know the tender points are no longer in vogue, so what do you recommend we do in primary care to make a confident diagnosis?

[Dr. Daniel Clauw]

Yeah. So thank you for saying tender points

are no longer in vogue. I would say they're stupid and stop

doing them, but that was a much

more polite way of doing it. And one of the problems with the original criteria that required a tender point

count is we didn't know that women

are a lot more tender than men. So those criteria, if you apply them in the US population, about 92% of

the individuals that would be diagnosed with

those original criteria were women. The new criteria, simply by eliminating the tender point count, are now fibromyalgia is

only 1 1/2 to 2 times more

common in women than in men. It used to be really easy, especially

for male physicians to say these are just neurotic middle aged female.

When fibromyalgia was an almost an exclusively female disease. And now that it's really more like all pain conditions are about 1 1/2

to 2 times more common in women than in men. We are pretty sure that that's because again, women are more sensitive to pain

and other sensory information in their central nervous system.

They don't have more damage out in the tissues. But it seems as though that the reason almost all chronic pain conditions are again, 1 1/2 to 2 times more

common in women than in men is they're more sensitive centrally to both painful

stimuli and non painful sensory stimuli.

If it wasn't annoying enough to be

a female in this regard, if you're still actively menstruating, you'll get more sensory sensitive and more pain sensitive in the premenstrual phase of your cycle.

So that's just something about that's different.

And that's why probably the biggest single

risk factor for developing nosoplastic pain is being female.

In that again, we know that it's always going to be quite a bit

more common in women than in men. But the old fibromyalgia criteria, people wouldn't

even think of the diagnosis of fibromyalgia in a man.

And these were the men that got

so called failed back syndrome because no

one even thought that their pain in

their back could be a central cause.

And they had five surgeries that made

their pain worse and worse and worse.

[Zoya Surani]

Ugh.

[Dr. Matthew Frank Watto]

So is it enough to just do the history? I know there's the Widespread Pain index and the Symptom Severity Scale, which I've used, and it's a form you can fill out with a patient. Is that a reasonable step for Paul? We call Paul America's primary care physician. So for him, if he has someone he suspects of fibromyalgia, is it okay to use those questionnaires to try to diagnose them?

[Dr. Daniel Clauw]

Yeah, I think that the fibromyalgia questionnaire is the best questionnaire to use.

And one of the things that I like about it is it forces you to give people a body map and indicate on a body map where they're having pain. Because sometimes you don't, in a history, you don't pick up on all the

different locations they're having pain in. I've written editorials about this in our pain journals.

Is why don't we use a body

map in every single person with pain?

Because if you have someone fill out a body map and they have pain

in three or four different regions of their body, like one arm and one

leg, they have nociplastic pain. Unless they have some weird autoimmune disease that causes pain in those locations of the body. But a body map alone can tell

you a tremendous amount about the type of pain that you're taking care of.

And again, it's helpful to have people check where they have pain because sometimes

the pain that they'll check on a

body map is not detected as part

of a regular history.

Cause you zoom in too rapidly on

the chief complaint of where the pain is the worst.

[Dr. Matthew Frank Watto]

Yeah, I don't think I've used the fibromyalgia questionnaire specifically. So that's different than what I was asking about. Cause the, the widespread pain index does have like, I think it has 19 spots where people can say if they have pain. Can you talk a little bit more about the fibromyalgia questionnaire, what's included with it?

[Dr. Daniel Clauw]

Yeah. So what you're using is what was

called the 2010 criteria where the clinician

had to ask someone about the pain in those 19 areas of the body. Now most of us do that, the WPI, by giving someone a body map that has those 19 areas of the body. And we ask them to check the body map and you add up how many of those 19 sites. But by doing that and handing well,

it's easier to have the person fill it out rather than you asking all those questions. But it's probably more accurate in that you really will pick up on pain that the individual is experiencing, but is

maybe below the threshold where it comes

out in the initial part of the chief complaint or the history of present illness.

[Dr. Matthew Frank Watto]

Okay, perfect. So what would a first office visit look like for this person coming to you? They saw their primary care, this 42 year old woman, she already had some imaging, she had a bunch of rheumatologic serologies and all sorts of testing that all came back looking normal. And now she's wanting to know what's going on here. So would this be enough for you to diagnose fibromyalgia? Let's say she fills out the questionnaire and she has pain at nine different body sites. Would that be enough for you to say this is probably fibromyalgia?

[Dr. Daniel Clauw]

Yes, but I would first try to

think of some way that I could

convince her that this was fibromyalgia.

And again, this is where I would

often ask about, are you bothered by bright lights?

Are you bothered by noises? Do you have a lot of these kinds of symptoms so that you can

tie together in that person's mind some of the disparate symptoms that they'd been

having, you know, maybe that they didn't even initially report. But that's a good way to get people's confidence that. Because you're not going to. You're not. You don't have an objective diagnostic test. So you want to give them the

confidence that you're quite certain that this

is what it is.

Even though you can't order a lab

test that says, aha, this is what it is.

[Dr. Matthew Frank Watto]

Yeah. Paul, do you remember we have a friend, Dr. Iris Wang, who does a lot of treatment for disorders of gut brain interaction? And she says to patients, when she suspects they have epigastric pain syndrome or irritable bowel syndrome, she'll say to them, I'm going to be doing some testing, but I expect it to be negative because I think this is what you have. So she's sort of making it like a. I'm already sort of made. I've made the diagnosis pretty much. I'm just doing this to make sure it's not. I'm not missing anything, but I'm pretty sure I'm not missing anything. It sounds like it's a similar thing here where you sort of trying to convince them. This constellation of symptoms, I see it all the time. This is. This is caused by the brain, and we term this fibromyalgia. Do you also bring in the. We mentioned a little bit off air before we started, the multiple allergies or intolerances to medications. Is that another one that's helpful to bring up in this kind of conversation, trying to convince people?

[Dr. Daniel Clauw]

Yeah, we've sort of thought this for a long time, but we now finally

have data showing this that the number of quote unquote drug allergies that someone has is another clue to the fact that someone might be sensory sensitive. Because a lot of those are not true allergies.

If you really interrogate people, they're really hypersensitivities.

And especially what you see is that

a lot of those hypersensitivities are to medications that are CNS acting.

So they might have one true allergy

hidden in that list that is a

true allergic reaction, but the rest of

them are really hypersensitivities.

And again, a lot of them, if you look at the hypersensitivity, it's sort

of like anteroceptive symptoms that the person

has when they took a certain medication. Nausea, palpitations, things like that.

Given that their sensory nervous system is

sort of on fire, you can imagine that almost any drug, especially any sort of CNS active drug, is going to be not as well tolerated by these individuals as by someone that doesn't have

this sort of hyperactivity of their sensory

[Dr. Paul Nelson Williams]

processing, as is the curbsider's way. We usually skip from history. Right. To diagnosis. I do want to at least throw a SOP to physical exam and ask, is there anything you look for specifically, or do you use that to rule out other potential things, like, are you looking for, like, synovitis or other signs of autoimmune? How do you use the physical examination when evaluating patients to present like this?

[Dr. Daniel Clauw]

Yeah, so I was trained as a rheumatologist, and I do think it's helpful

to do a good musculoskeletal exam in these individuals.

But instead of doing a tender point

exam, what I'll do is palpate with

pressure over the interphalangeal joints in the fingers and then over the wrists.

But really looking for synovitis, I get

a lot more concerned if I'm seeing someone initially that maybe has, like, early symptoms. And when I palpate that, their tenderness

is really localized over the joints, because

that could really be early arthritis, early

rheumatoid arthritis, early synovitis.

And those are individuals that I'm a little more concerned.

Whereas if I palpate and they're tender,

a little bit tender over, like, the

middle part of the phalanx, and then when you go up the forearm, they're

tender in the forearm.

That's what I would expect to see

in someone with fibromyalgia.

Not looking for tender points per se

at all, but diffuse tenderness.

And again, the thing that I worry about is tenderness that's sort of localized to joints or localized to specific areas where you'd say, ah, this could be something else.

[Zoya Surani]

Okay, so for the same patient you've diagnosed fibromyalgia, Given her history and physical exam findings that were negative for any signs of synovitis. She then asks, what medications can I take to help? Her most bothersome symptoms are poor sleep, fatigue, and diffuse pain. Her only other medical condition is depression, but she's not currently on any medication for this. She works as a teacher and says the brain fog is affecting her job performance and she's worried about having to take time off if she can't get this under control. So one of my questions was before we get into treatment recommendations, she has a comorbid history of depression. How often do you see these conditions coexist with fibromyalgia?

[Dr. Daniel Clauw]

Very.

But one of the points I want to make is that more often there's a bidirectional relationship between anxiety and depression and chronic pain.

But I think that most clinicians or many clinicians think that often the psychiatric

condition came first and that that sort of led to the pain.

But a lot of studies are showing is that if you take someone with

fibromyalgia or with nociplastic pain, if you do something to make their pain better, often their anxiety and depression goes away,

their catastrophizing goes away. A lot of these psychological symptoms that

we see are the consequence of having pain, often for many years or even

decades that someone would.

This individual has already gone to three different providers, none of which offered any help.

They just did a bunch of testing.

They didn't really do anything. And the longer that people have this

journey of going from doctor to doctor to doctor, no one really explaining what's

wrong with them or doing anything that

makes them better, I think anyone would start to get more anxious and depressed

and quote, unquote catastrophizing. And so again, I think it's really important for clinicians to understand that a lot of that psychological comorbidity is likely to be the result of sort of

untreated pain for many, many years.

And if you can do something to make that individual's pain better, they might not have such sort of florid like psychopathology.

[Dr. Matthew Frank Watto]

Dan, when I Talked to you 10 years ago, something that stuck with me and let me know if this is still true. But we were talking about chronic pain. You were saying that with medications, thethe average, if someone has chronic pain and on a scale of 10 points, like the most pain medications are only gonna drop them like less than 2 points on a 10 point scale. So if they're coming in saying their pain's a 9 out of 10, you might make em a 7 out of 10 if you're lucky with a pain medication that they're gonna take chronically. I don't know if that's still true, but I always think of the non pharmacologic therapy as being more important for these patients. Is that still true and should we talk about that first since that's what we are going to want to put as our first line, or should we jump into medications?

[Dr. Daniel Clauw]

Yeah, let's talk about that first. Because I do think that the non pharmacologic therapy. There's certainly far more non pharmacologic therapies that work in fibromyalgia or that work in pain than there are drugs.

And that's probably one of the biggest differences.

When I published a review article on fibromyalgia in JAMA in 2014, the only

things up in the high evidence for

non pharmacologic therapy were aerobic exercise education and cognitive behavioral therapy. And there weren't very many things even in the modest, There were a whole bunch of non pharmacologic therapies that were

down in the low amount of evidence. One of the things that's helped a

tremendous amount is that when the NIH formed the institute that used to be called complementary and alternative medicine, it's now integrative medicine.

That led to a lot of studies

of what we now refer to as integrative therapies. Yoga, tai chi, acupuncture, acupressure, mindfulness, all sorts of different therapies that we used

to be dismissive of.

Certainly when I trained, we were dismissive of virtually all of those therapies. This would even include things like myofascial release, chiropractic manipulation.

All of those things that I just

mentioned now have a pretty good evidence

base for use in chronic pain and

especially for use in conditions like fibromyalgia.

And instead of just aerobic exercise, which

I was talking about in 2014, any

kind of exercise is good for people with this condition.

And one of the teaching points I would make is when you talk to the individual with fibromyalgia about exercise, don't

use the word exercise because they'll look

at you like you're stupid.

Use the word activity because actually that's.

Usually people with fibromyalgia have become fairly sedentary, and your first phase is getting them moving before you're really getting them

to do anything that we would really call exercise.

And that helps a lot. I think a lot of people learned

that during the COVID pandemic, when a lot of individuals like sat for hours

like doing zoom and things like that. A lot of people that didn't have anything resembling fibromyalgia got achy and started feeling cruddy just because prolonged inactivity is

not good for you.

And so I say that the basic tenets of treating fibromyalgia are get people

moving and get them sleeping, those two core things to work on.

And there's a lot of things you can do to get them moving. There's a lot of things you can do to get them sleeping, but but

really work in both of those domains fairly aggressively, starting with non pharmacologic approaches.

And then certainly you can use drugs

to help with sleep. But that I think is the starting point is to really encourage people to become more active rather than using the

term exercise, and encourage them to do something like walking.

That's relatively easy for almost anyone to do.

Start at a very low amount and

go up very slowly. Because these individuals, if they do too

much activity or exercise too soon, will

get much worse and will get very

frustrated and even say, oh, you know, exercise is bad for me, or exercise.

Certainly the individuals with more of the

chronic fatigue phenotype, they've almost been taught by the patient advocacy groups that exercise is toxic. They can exercise.

That's not true at all.

But they have to do very slow,

gradual, graded exercise and go up very gradually or they will often make themselves worse.

We just wrote an editorial. I think it was in one of the JAMA journals. There was a study that showed that

physical therapy with the use of a TENS unit in fibromyalgia was helpful. But in this study, we were asked to write the editorial.

The study compared individuals getting physical therapy

alone to physical therapy plus a tens. And this was done in community physical therapy practices.

It was a pragmatic trial. And when we were asked to write the editorial, the most striking thing to Afton Hassett and I that wrote the

editorial was that the group that got physical therapy alone had no improvement in pain in the course of this trial, whereas the group that got physical therapy plus tens had a mild improvement.

And that was statistically significant. So the editorial that we wrote is not all physical activity is good.

Some physical therapists, especially ones that are trained to do like sports medicine and

things like that, probably routinely make these people worse. So don't think that just because activity and even exercise is helpful for fibromyalgia that every physical therapist is comfortable taking

care of these individuals or every physical

therapist is gonna know how to get

that individual with fibromyalgia to get into

a home exercise program. That's gonna make them beneficial. This pragmatic trial, if you see at

the end of a randomized control trial that a group has no change in

pain, that means that half of the

people had a worsening in their pain

and half of the people had an improvement in their pain to get a

mean of no change.

And that's what we said in our editorial.

And I mentor a lot of physical therapists now. That will acknowledge that there's a lot

of stigma amongst pts about these patients

because this isn't how they were trained.

And just like there's a lot of MDs and physician providers that are still uncomfortable taking care of these patients, it's

true of physical therapists, even though theoretically they would be the right group of

people to get people to more active

and to promote the use of physical activity.

[Dr. Paul Nelson Williams]

And Dan, probably knowing your local resources is helpful in knowing what physical therapists do have comfort. But are there any videos or resources that you direct patients to to kind of help them find programs that might be helpful for them? Like how. What kind of specific directions do you point folks in to kind of come up with programs to degradedly increase their activity?

[Dr. Daniel Clauw]

I think it is local. I think you figure out which of

the therapists in your region are good

at taking care of these patients. And if you don't know, if you go to one of these practices that don't like fibromyalgia patients, they'll tell you they don't like, they're not bashful. And so would you ask them, do you have a therapist that specializes in

taking care of fibromyalgia?

And if they can't say yes, then

go to a different PT group that

does have such a therapist. Because there's a lot of therapists that

are quite good and have learned how

to incorporate elements of cognitive behavioral therapy and even mild amounts of pain reprocessing

therapy into their scope of practice of being a pt. Those therapists are great for these patients.

But someone whose day to day practice is sports medicine taking care of the using the no pain, no gain exercise

thing, those people will put a fibromyalgia patient in bed for a week and

they won't ever think that exercise can be helpful to them because of that negative experience they had with someone that just simply pushed them too hard.

[Dr. Paul Nelson Williams]

Yeah, it's the number of times you heard I tried pt, it didn't help me or it made things worse. And then that's just kind of the end of the conversation. That absolutely tracks.

[Dr. Matthew Frank Watto]

Dan, I wanted to ask. So when we're talking about non pharmacologic you mentioned like patient education is one of the big things, right. And then you said move and sleep, those are the other things. And then all the integrative therapies like yoga, Tai chi, all these things that are kind of moderate evidence, those are things we can explore with our patients. I wanted to ask for patient education. I think last time you had given us there was A video you had done on YouTube that you would, I think you would have your patients watch it. Do you still have a video like that that's publicly available or a resource to help like augment patient education? If our, let's say our people listening to this are in a 20 minute visit with somebody, they can only do so much. So what's a good resource to help with patients? Self education.

[Dr. Daniel Clauw]

Yeah, we have a website that's free. We don't get any money from it, we just use philanthropic funding to put it together.

And it's actually been tested in a lot of trials. It's called painguide.com just all one word,

painguide.com and it's got a tremendous amount of information about all of these non pharmacologic therapies. It has videos.

If people want to learn how to self administer acupressure, there's mp4 files they

can download to do meditation and mindfulness. But it's got a treasure trove. It's got too much information in it, so patients will often get lost in it. But certainly for a provider, if you really want to work with patients and say let's work this time on sleep, go to this website, read all that

whole chapter and those modules about sleep.

It's got all the sleep hygiene things and things, but I think it's a really good tool to send the patient to between visits as a way of

getting more intense training in one of the non pharmacologic therapies you want to

try or some of the concepts you want to work on like goal setting. But it basically takes a lot of the elements that are part of pain,

cognitive behavioral therapy and puts it all

on a website and sort of makes it easily accessible to both any patient

but also to providers. And there's a lot of short videos

in there to help explain nociplastic pain

central sensitization to individuals as well.

[Dr. Matthew Frank Watto]

Well, I think that a lot of patients with chronic pain, if they haven't been caught early enough and come across someone like yourself that's going to educate them and point them towards like things that they can do non pharmacologically. A lot of people want passive things done like they want someone to do a surgery on them to fix their pain or they want to take a pill that's going to fix their pain. And sometimes once someone's already started down that path, it can be I think really challenging for us. But how, how would you talk to someone like our patient here, this 42 year old woman, we just diagnosed her with fibromyalgia. We gave her our spiel about non pharmacologic stuff. But if she wants a, a medication, how would you go about deciding if anything's right for her and what are some agents you'd consider?

[Dr. Daniel Clauw]

I'll talk about the medications, but you

keep reminding me to say one more

thing about the non pharmacologic therapies before we go on to the medications.

Each of about 15 or so non pharmacologic therapies we've listed, most of them works in about one out of three individuals with chronic pain.

So what I say to patients is

here's a long list of these non

pharmacologic therapies that have been shown to be effective. Look at the list and pick out three of them that you're going to

try in the next year. And it's likely if you really try

three of them, you're going to find

one of them that works really well in you and you will retain that and you will forever be at a

new level, a new plateau of better functioning because you've integrated yoga or Tai

chi or acupressure or mindfulness.

And I like how you talked about, we prefer the active therapies to the passive. The active therapies where the individual has

to play a more active role themselves in doing them.

Things like myofascial release, acupuncture, things like that, that someone has to go and

get someone else to do work and they're fine. But we really like, that's one of the reasons that we've studied acupressure a

lot, because it can be self administered

or you can have a family member

administer acupressure and it's not the going and getting someone else to make you better. We really like to try to empower individuals with chronic pain to play an

active role in their own treatment.

[Dr. Matthew Frank Watto]

Let's say we have our patient trying some Tai chi and starting to do a gradual exercise program, starting to do a little bit of work on her sleep and she still wants something for the pain. Maybe she goes to a local dispensary for cannabinoids and tries those. She floats that idea. How would you respond to that? And would you point towards pharmacologic therapy? Paul, I know you want to hear about cannabinoids.

[Dr. Paul Nelson Williams]

I always, it's an important hobby of mine.

[Dr. Daniel Clauw]

Let's talk about the approved drugs first.

And I'm happy to talk about cannabinoids

because we actually are doing a lot of work in cannabinoids.

[Dr. Matthew Frank Watto]

Yes. And by the way, Dan, I'm joking with Paul. He's generally skeptical of cannabinoids because I think how widely they've just.

[Dr. Daniel Clauw]

Right. Well, so am I. So there are now four approved drugs for use in fibromyalgia. The last one to get approved in the past year was sublingual cyclobenzaprine, which I really like.

Cyclobenzaprine.

I've been using that drug for 30 years.

And I think the sublingual formulation makes

it a lot easier for people to start and easier to take. It's a really low dose. It's incredibly well tolerated.

And so I like starting people on

cyclobenzaprine because it's the kindest and gentlest of any, certainly of the approved drugs that we have.

I also probably my second favorite drug would be duloxetine.

Again, people are aware of the side effects of duloxetine, but I think that

it's really helpful for a lot of patients. There's a sort of a relative of duloxetine, milnacipran, which is an approved drug

in fibromyalgia, but it's not really very well tolerated.

It's quite a bit more noradrenergic than

duloxetine, and it causes palpitations and things

like that in a lot of individuals. And then the fourth approved drug is pregabalin. And there doesn't really seem to be a big difference between gabapentin and pregabalin.

And so I would just put sort of gabapentinoids as the class of drugs that you could use for fibromyalgia.

Again, I think everyone knows that there

are issues and problems with gabapentinoids, as well as with serotonin, norepinephrine, reuptake inhibitors like duloxetine. But those drugs can help a lot

of people, and those are sort of the preferred drugs. There's a couple other drugs that are not approved but are worth trying. Some of the other older tricyclic drugs.

Cyclobenzaprine is actually a tricyclic, even though many of us know it as flexeril,

which was marketed as a muscle relaxant.

It's structurally almost identical to amitriptyline.

And so that's probably when we're using

cyclobenzaprene to treat fibromyalgia.

We're just taking advantage of a low

dose of a tricyclic.

But other tricyclics you could use instead

of cyclobenzaprine would include Amitriptyline, nortriptyline. But again, in my hands, even before

the sublingual formulation came out, when we

were just using regular old cyclobenzaprene, I always found that of the tricyclics, that was the one that was the best

tolerated and had the best overall sort

of effectiveness in individuals.

[Dr. Matthew Frank Watto]

And this is a 5 milligram dose in the evening that you're giving the sublingual form.

[Dr. Daniel Clauw]

If you give the tablet, you can give a 5 milligram tablet.

The sublingual form is 2.8 milligrams.

And people start by taking one of those sublingual for a couple weeks, and then they go up to two. So they're taking. At the end, they're taking a little

bit more than 5 milligrams of cyclobenzaprene.

Obviously a really low dose, The Flexeril

was 10 milligrams every six hours. If you give flexeril at that dose,

or, I'm sorry, cyclobenzaprine at that dose to someone with fibromyalgia, they'll be obtunded. That's actually one of the things that

makes you comfortable that someone really has fibromyalgia is they're often exquisitely sensitive to

this low dose of a tricyclic drug, which is why.

And even tell patients that the first

couple nights that you take this, you may sleep so well that you have

vivid dreams and nightmares.

But that's what we're trying to do.

We know that much of the benefit of both cyclobenzaprine and of the gabapentinoids

seems to be in promoting deep sleep.

And so those two classes of drugs

are the preferred hypnotics if you're trying

to get people with fibromyalgia to sleep better.

Cyclobenzaprine would be my first choice, and

pregabalin or gabapentin in a single nighttime

dose would be my second choice.

But both of those classes of drugs have been shown in studies that much of their benefit in fibromyalgia is on polysomnography in improving the deep sleep that people with fibromyalgia generally don't have.

[Dr. Matthew Frank Watto]

Oh, wow.

[Dr. Paul Nelson Williams]

And do you see improvements in pain with this? And if so, do we think that's related to the better quality of sleep? Or is there some other. Or is it related to some other activity? Yeah, this is all fancy because with low back pain, I feel like we throw cyclobenzerpen in people. And the joke is it may not help your pain, but at least you'll be able to sleep at night. So this is kind of in keeping with some of the other uses I've seen for it. But I would love to hear about the effects in this particular patient population.

[Dr. Daniel Clauw]

No, typically people will first note that it makes their sleep better and then their pain gets better and their fatigue

and everything like that gets better.

But.

And a lot of other studies in central sensitization, nociplastic pain.

If you look in the general population, like epidemiologic studies, the strongest risk factor

for someone developing new fibromyalgia is insomnia at baseline. So if someone has insomnia in epidemiologic

studies, their risk of developing fibromyalgia in

the next year is about two and

a half times greater than someone that doesn't have insomnia.

Whereas if they have, for example, stress

or anxiety or depression, the relative risk is increased by like 50 to 60%, but not 250%.

And so the, often the sleep abnormalities

come before the pain.

And that is like.

There was a famous fibromyalgia researcher, Harvey

Moldowski, that did some famous studies in the 1970s that showed that if you

took healthy college students and sleep deprived

them, you could, in about a week

they would develop symptoms very reminiscent of fibromyalgia.

And the pendulum swung away from that

where we started to think that poor sleep was more of a symptom of fibromyalgia.

Now it's swinging back the other way

where we know that that often the

sleep problems antedate the development of the

pain and it's really important to treat the sleep.

[Dr. Matthew Frank Watto]

Well, we recently did an episode on sleep optimization like CBTI with a really great doctor who does cbt I. So she was very helpful for that. So our audience has a lot of tips on how to get their patients sleeping better. Okay, so the meds. So cyclobenzaprine at low doses, duloxetine, the gabapentinoids. You said if we can also try the older TCAs, Amitriptyline, Nortriptyline and milnacipran. I've never prescribed that one. I know of it. You know, I see it whenever I read reviews about fibromyalgia. But, Paul, are you prescribing that one? Have you prescribed it before?

[Dr. Paul Nelson Williams]

No, I'm grateful. I didn't have to try and even pronounce it. So that's my familiarity with that.

[Dr. Matthew Frank Watto]

And the other thing that always gets asked about or oftentimes patients will come to us. They're on Opioids for fibromyalgia. Can you talk about that? And we'll save cannabinoids for next. But opioids and even tramadol. I know tramadol has a little bit of opioid agonism, but it's maybe the Snri effect that is actually helping with the pain and fibromyalgia anyway, but can you talk about those?

[Dr. Daniel Clauw]

Yeah. I hate pure mu opioids for use in pain in general.

I've testified in litigation in several states against the opioid manufacturer. So I just want to be clear

where I stand on this issue.

But

there really was never even a

single study that used a parallel group design that showed that pure mu opioids like oxycodone or hydrocodone are effective in

any chronic pain state that might blow you away. That there's not a single study, but all of the studies were using this

enriched randomized withdrawal design where they put

someone on an opioid and then they took half the people off and left half the people on. And they looked at like, did the

people feel worse when they got withdrawn from the opioid?

Well, they were dependent on the opioids. They were going through opioid withdrawals. So I've written about this. I think there's still far too many opioids used in the United States to treat chronic pain. But I think that in particular in

fibromyalgia, it's not just that they don't work. Many of us worry that pure mu

opioids often will make people worse. We did a study that we published

several years ago where we used PET

imaging with carfentanil, which is a highly potent opioid. And in the same individuals, we did

functional mri and it looked like on the PET imaging that the fibromyalgia patients were over releasing their endogenous opioids, endorphins

and enkephalins, which is what you expect they might be doing because pain causes endorphin release. And so if someone has pain all

the time, they're bathing their brain in

their own endogenous opioids. And we call this endogenous opioid induced hyperalgesia. That these high doses of their own endogenous opioids for long periods of time are causing what we know as opioid induced hyperalgesia.

That in animals or humans, if you repeatedly dose someone with opioids, you can

get them to wind up and they

get more pain sensitive. And so that study really concerned me that we have a biological mechanism by

which you really could be making someone's pain worse by giving them an opioid. And there have been several trials done in the last couple years. The pharmaceutical companies never did these opioid trials, but there have been several trials that have been published in the last couple years that actually make it look

like there's a subset of people who indeed it's not just that the opioids

don't make their pain better, the opioids make their pain worse, but it's insidious. The longer they're on happens very gradually, happens very slowly. And these people are like very physiologically dependent on opioids. So it's almost impossible to get them off of them.

Yet the opioids are not benefiting them. And so the biggest suggestion I have, and I just want to be clear, everything else that I've said today, there's

data and evidence to back up.

This doesn't have any data or evidence. But I strongly believe that if you

have to use an opioid in people with fibromyalgia, buprenorphine would be by far the best opioid.

And it's because of the antagonist, the

opioid antagonist properties in bup that I

actually think it would be a good opioid to use in nociplastic pain or fibromyalgia if you had to use an opioid. Some of the other mixed opioids like

tapentadol, which is an opioid plus a norepinephrine reuptake inhibitor, or even tramadol, which as you mentioned is a serotonin norepinephrine reuptake inhibitor plus an opioid.

If you have to use an opioid,

use a mixed opioid, but don't use

a pure mu opioid, an oxycodone or

hydrocodone derivative, which is about 80% of

the opioids used in the United States

as long term opioid therapy are oxycodone hydrocodone derivatives.

[Dr. Paul Nelson Williams]

This. I know we hadn't actually broached this topic yet, but this feels like the right time to bring it up. I hope you don't buy Matt, but what about low dose naltrexone? Just as we're talking about sort of opioid receptors, I've seen that sort of broached as a medication for sort of chronic inflammation or chronic pain and fibromyalgia specifically. What's the current thinking and what has been your experience with that medication?

[Dr. Daniel Clauw]

I Think it's worth trying.

The data aren't great and there's a meta analysis that suggests that it probably isn't very helpful. But the people that I know that are, again, I'm not practicing anymore, but that are actively practicing seeing a lot of fibromyalgia patients do say it's helpful

in maybe a third or so of patients.

It certainly seems to be well tolerated and safe. And so I think it's well worth trying. It's a little bit of a hassle for people to, you know, get it from a compounding pharmacy, but I think it's worth trying and I would put it up there as something that, you know, that you would be, you know, wanting to try.

[Zoya Surani]

I had a question, kind of going back to the opioids, especially patients that have been on opioids for years. How do you navigate the conversation about making medication changes or lifestyle changes to help manage their pain better?

[Dr. Daniel Clauw]

The first thing is don't try to

take the opioid away from the person. Try to convince the person that taking the opioid isn't in their best interest.

And there's a couple little factoids that I like using and, and I, and, and I don't recommend using these all in the same visit. If you, if you want to try to get someone off an opioid, realize you're not going to do this by playing checkers.

You're going to have to play chess.

You're gonna, you're gonna, this is gonna take a series of like little like, you know, messages and things like that

to try to gradually move them. So here's a couple factoids.

The one that I think is the

scariest and the reason I hate opioids

the most is that I don't think people know that if someone is taking

long term opioid therapy, their all cause mortality is doubled.

And people think that most of the

problems associated with taking opioids are related to addiction.

They're not in chronic pain patients.

I don't worry about addiction at all.

But if someone's on long term opioid

therapy, the rate of myocardial infarction, of

motor traffic accidents, of suicide, there's so

many different reasons they die at higher rates when they're on an opioid that

it's hard to increase your all cause

mortality by like double it.

You have to drink like, like 18 drinks a day to double your all cause. So people don't understand. I don't think that doctors that prescribe

opioids or that patients that are Taking

them really understand is that, is this

drug, do you know for sure that

this drug is helping you so much

that you're willing to double your risk of dying next year?

And the other thing that I think

is really helpful to tell individuals that

are on opioids is are you aware

that if people slowly gradually taper their opioids that at least half of patients will have an improvement of their pain or no change in their pain when they taper their opioid? At least half the studies are mixed.

It may be as high as 60% or so of people that are.

And again, what I try to get the person to answer for themselves, I don't try to answer this question for

the do you know for sure that that opioid is helping you enough that

you're willing to put up with that increase in all cause mortality and looked at with a side eye every time

you come to the emergency room or

your pharmacist doesn't want to refill your prescription? Like all the things associated with taking an opioid, do you want to put

up with all of that when we don't even know if you're one of

the people in whom if you slowly

gradually tapered this drug, you would feel better.

But again, you have to really slowly, gradually move people along that path to

get them to understand.

And one of the ways I think to do that is to introduce other

things that do make them better.

Because even if you do get someone

to the point that they're willing to

slowly taper their opioids and the other thing is tell them is that if

you taper your opioid and your pain gets worse, you go back up to

the opioid dose you were on before.

I'm totally okay with that.

Like that's. Then at least we know you need the opioid. But all I want to do, Mrs.

Jones, is make sure that you're not one of the people, one of the

millions of people that was put on these opioids. Very well intentioned, but now we know

that a lot of these individuals would do far better if they weren't on the opioid. Do you know for sure that you're not one of those people?

And so let's try this. But if you try it and your pain gets worse, then you go right back up to the same.

I'm not taking them away, I'm just asking you to be sure that they're helping you enough that you should keep taking them.

[Dr. Paul Nelson Williams]

I think that's an amazing framing because the Patients who are on chronic prescribed opioids are not on them for the love of the game because as you mentioned, it is a hassle to keep calling back to your doctors and getting prior authorizations and coming in for your own drug tests and signing control. No one enjoys being on chronic opioids. So if you have a contingency plan or at least offer some sort of backup if the tapering doesn't work, I think that's a terrific framing.

[Dr. Daniel Clauw]

And then someone that I work with that tapers a lot of people off opioids told me once that he gives

every person his cell phone number and

says call in the middle of the

night if you have a problem. He's never gotten a call.

But having that cell phone number, the patient's knowing that they're not gonna get dumped. You know that this isn't like an opioid taper where if I my pain gets worse, you're gonna make me like keep taking that lower dose of opioids.

That's not what we're doing here. We're just asking you to be sure

that you still need these drugs. And it goes along. The other thing I think that resonates

a little bit with many individuals is this isn't the only class of drug we're deprescribing now because we're realizing that

people are just get on, they accumulate

drugs and you know, do we still

know that someone needs this drug or this drug?

So there's a lot of drugs like this.

I think that we're, you know, that

we're thinking about deprescribing because we know that there are significant long term side

effects of continuing to take many drugs, especially opioids.

[Dr. Paul Nelson Williams]

Yeah, Matt, I don't know if you remember, and then not to stay too long on this topic, but talking to Stephan Cortez, I think a couple years ago about the forced opioid tapers and the catastrophic results that happen with those. So if you don't have patient buy in and you just sort of taper things because that's what you were told, it can have really, really bad outcomes. So getting the patient buy in, working together and making them feel not abandoned is really critical. So I love those points.

[Dr. Matthew Frank Watto]

I think we should end by just getting your hot take on cannabinoids.

[Dr. Paul Nelson Williams]

Hold on, Matt. Yeah, thank you. I was going to say I hope you're not getting the take home before

[Dr. Matthew Frank Watto]

we heard about cannabinoids because, Dan, I think cannabinoids, at least on the east coast, anywhere you drive the highway is just filled with billboards of all these dispensaries. And pretty much it's just anybody can get a cannabis card. It's almost a joke. And I think there's kind of a belief that it's like a panacea. It's just going to work for everything. And most people taking using it, in my opinion are still struggling with one thing or another. So I don't think it's really curing much. But has it been helpful in fibromyalgia or has it been studied?

[Dr. Daniel Clauw]

We have a lot of ongoing NIH funded studies.

It's nice that starting about four or

five years ago, the NIH started funding

studies showing that there could be a benefit of cannabis.

We have a bunch of studies that

will read out in the next year or two. We don't know.

There has been a couple studies showing that synthetic THC nabilone, a synthetic cannabinoid,

was effective in fibromyalgia.

I think the biggest problem with cannabinoids

is people are taking way too much.

So if people don't get the appropriate guidance and advice. One of our studies right now that's funded by the state of Michigan, because we have entirely legalized cannabis, people don't need a card. It's legal. Is a coaching program where we coach people that are wanting to use cannabis

to treat their pain.

But the randomization in this trial is coaching versus go in the wild west the way you're using it on your own. Because we think that people that there may be some therapeutic benefit, but rarely are people seeing it because they're using it all wrong. They're not using the right route of administration. So a couple things.

No reason ever to inhale a cannabinoid for medical use. The route of administration should be oral

route of administration because that you don't

get a really big peak in the

drug level that causes the likability and gets you high. That's why all drugs of abuse are

smoked or snorted or injected because that

rapid rise in the level is what makes you high. So first thing is use an oral route of administration. But the main thing is if you're gonna use anything THC containing, I'm holding out hope that CBD alone might be

helpful for certain types of pain because it's super safe.

But if we're now talking about anything that involves anything that contains thc, the

studies are pretty clear. A low amount of THC works better for pain than a high amount of thc. And I think that the overwhelming majority of people who are Going to these

dispensaries and using, trying to get pain relief using cannabis. The strains that are now being sold

in the stores are catering to the recreational users that want to get high,

super high potency strains.

And I think most people are totally overshooting the low dose that might be helpful.

We think that it's possible that especially

a low dose of THC at bedtime, maybe 5 milligrams, 7.5 milligrams of THC

at bedtime might be useful. But again, if you look at what people are really taking now, and it's

way more than that.

And again, so this coaching program that

we're testing, it teaches people both about

like route of administration as well as

how to read the things to get

and to start out at a really low amount of thc, start by taking it just at bedtime and then maybe

expand out a little bit from there.

But I think it could have some potential.

But I share your general concern that most people who are using it are just getting high.

They're not getting. And I think it's very similar to opioids.

A little bit of opioid used for acute pain intermittently works incredibly well. The higher the dose of opioid you use and the longer you use it for, the less well it works for pain.

Cause what happens is the body's own

endogenous system, the longer you give the opioid, you just shut off production of

the endogenous opioid system. And the same thing is probably with cannabinoids. When people use these high doses of

cannabinoids, they're probably shutting off the production of endocannabinoids. And that may very well be what leads to the hyperemesis syndrome.

And some of the other things is that if you don't have your endogenous cannabinoid system, protects you against nausea and things like that. And if that's not working because you're taking high amounts of THC that have

basically shut off your endogenous production of

cannabinoids, that all of these things that the endocannabinoid system does, just like when

a long term opioid user, when they

shut off the endogenous opioid system, there's

all sorts of things that those hormone

systems do in us other than treat pain and you end up by hijacking those systems to treat pain, you often have these off down target effects on

all these other systems.

[Dr. Matthew Frank Watto]

Paul, does that satisfy your cannabinoid questions? I thought that was a pretty good answer. I learned a lot there.

[Dr. Paul Nelson Williams]

Yep, that was great. Thank you.

[Dr. Matthew Frank Watto]

Well, we've taken so much of your time, Dan. This has been fantastic. I would love it if you could give the audience just like one or two take home points, what you want them to really remember about this episode, about this discussion that we've had.

[Dr. Daniel Clauw]

Fibromyalgia and nociplastic pain are very real.

We are beginning to understand the neurobiology

of these conditions better and better.

And I think that these individuals can

often be treated quite effectively if they're identified early and treated early.

I think one of the biggest problems that we have with fibromyalgia is that

the average fibromyalgia patient, it might take

six, seven years to get the diagnosis. And an analogy I use because I'm trained as a rheumatologist, is if you wait five years to treat someone's rheumatoid arthritis,

most of their joints are going to be destroyed.

And there's so much of it that

becomes irreversible when you wait and you

take that long to start treating a disease.

Most diseases are like that.

And I think that what happens with

conditions like fibromyalgia is we should be

identifying these individuals in their teens when they've developed their second chronic overlapping pain condition. And it's like if we don't get you sleeping and exercising and you're gonna be on the path to be this

fibromyalgia patient at age 40 that none of us can make better because there's been too much.

And what chronic pain patients accumulate is all the psychological and functional consequences of having pain that really gets it be

firmly entrenched and really very difficult to treat.

So I think that if we identify

these individuals much earlier in their lives

and treat them aggressively with a lot

of non pharmacologic approaches, stay away from

opioids, use, you know, one or two

medications, especially the drugs that are gonna

help get them deep sleep. That I think we actually could do

a much better job of treating these individuals.

[Dr. Matthew Frank Watto]

And other than going to paingguide.com where they can get resources for them, for themselves or their patients. What else would you like to plug to our listeners? Any other places you want to direct them?

[Dr. Daniel Clauw]

One of the faculty in our group,

Afton Hassett, is a psychologist.

She wrote a book, Chronic Pain Reset, and she has her own podcast.

But it's really good because it's a

book that takes people through sort of

like a cognitive behavioral therapy. But I think it's a lot more approachable.

Cause people can just sit and read a book. And I think it's a really good book for patients to read.

I think she did a really nice job of sort of explaining why you do some of the different things that are under the umbrella of cognitive behavioral therapy.

[Dr. Matthew Frank Watto]

Yeah. All right, maybe we'll have to reach out to her for future chronic pain updates. That would be cool. Do a crossover.

[Dr. Daniel Clauw]

Yep.

[Dr. Matthew Frank Watto]

All right. Well, thank you so much for your time. I mean, this has been fantastic and I can't thank you enough. It's been great. 10 years. It's been like 10 years.

[Dr. Daniel Clauw]

I can't believe I'll see you in another 10 years.

[Dr. Paul Nelson Williams]

Don't you put that on us.

[Dr. Daniel Clauw]

You guys will be mid career then.

[Dr. Matthew Frank Watto]

All right.

[Dr. Daniel Clauw]

All right.

Okay. Take care.

[Dr. Paul Nelson Williams]

This has been another episode of the Curbsiders, bringing you a little knowledge food for your brain hole.

[Podcast Host (Closing Remarks)]

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[Dr. Paul Nelson Williams]

Sorry.

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[Dr. Paul Nelson Williams]

Perfect. Still hungry for more? Join our Patreon and get all of our episodes ad free, plus twice monthly bonus episodes at patreon.com curbsiders you can find our show notes, the curbsiders.com and sign for a million. You'll see our weekly show notes in your inbox, including our Curbsiders Digest, which recaps the latest practitioning articles, guidelines and news and internal medicine.

[Dr. Matthew Frank Watto]

Zoya, he was waiting for you to say yummy after he said knowledge food for your brain hole. But that's okay. It's optional. We're committed to high value practice.

[Dr. Paul Nelson Williams]

A more appropriate response. Really?

[Dr. Matthew Frank Watto]

That is more appropriate. We're committed to high value practice, changing knowledge, and we want feedback so you can email us@askcurbsiders gmail.com reminder that this and most episodes are available for CME for all health professionals through VCU healthcurbsiders.vcuhealth.org special thanks to our writer and producer for this episode, Zoya Serrani, and to our whole Curbsiders team. Our technical production is done by Podpast. Elizabeth Proto does our social media. Jen Watto runs our Patreon. Chris the Chumanchu moderates our discord. Stuart Brigham composed our theme music. And with all that, until next time, I've been Dr. Matthew Frank Watto.

[Zoya Surani]

This has been Zoya Surani and as

[Dr. Paul Nelson Williams]

always, remain Dr. Paul Nelson Williams. Thank you and goodbye.

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