Updates on Fibromyalgia & the Quest to Alleviate Pain

Chicago—In the current moment, rheumatologists can be forgiven for focusing on CART cells, bispecific antibodies and other dazzling new technologies that have brought with them a wave of excitement. But in the hustle and bustle of looking to the future, conditions like fibromyalgia have received even less attention than was previously the case (and indeed, this was already an issue for patients with the disease). In the ACR Convergence 2025 session titled, Ouch! What’s New in Pain?, two speakers shed a great deal of light on this important topic.

No Magic Bullet

The first speaker was Michael Kaplan, MD, an assistant professor of Medicine in the Division of Rheumatology at the Icahn School of Medicine at Mount Sinai, N.Y., who studies and cares for patients with fibromyalgia. Dr. Kaplan provided the historical context that explains why treating the condition can prove so challenging for doctors and patients alike.

With the emergence of germ theory in the mid-19^th century, medical doctors were able to successfully identify the discrete pathogens that cause infections such as anthrax, tuberculosis and syphilis. The concept of a “magic bullet” treatment—the term created by the German scientist Paul Ehrlich in 1907 to describe the idea of killing specific microbes that cause disease without harming the body itself—took hold and seemed to accurately reflect a reality in which illness could be objectively identified and summarily dealt with. Although these developments were undoubtedly beneficial to society—as indicated by improved life expectancy over the past century—it created a paradigm that applies well to certain diseases but not others.

When a patient with fibromyalgia goes to see a physician, they arrive with expectations that cannot be easily met even in the year 2025. They assume Western medicine has a magic bullet treatment to offer them, and that their doctor will have the time and patience to address the impact that pain has had on their life. But because there is no single, revolutionary pharmacologic intervention for fibromyalgia, and because of the systemic issues related to healthcare delivery and medical education (i.e., high patient volumes and inadequate training in chronic pain management), the doctor-patient interaction is doomed to fail from the start.

Recognizing this situation exists and pre-emptively addressing it, Dr. Kaplan explained, is therefore key to helping these patients. Dr. Kaplan noted he often shows patients a graphic illustrating how fibromyalgia so often co-occurs with other COPCs (chronic overlapping pain conditions) such as migraines, interstitial cystitis, irritable bowel syndrome (IBS), endometriosis and chronic fatigue syndrome. He explains to them the concept of nociplastic pain, which is defined as pain that occurs when the nervous system is overly sensitive or processes pain signals abnormally, even when there is no clear injury or nerve damage. Dr. Kaplan will often tell patients, “If you came to me with an infection, I would prescribe antibiotics, and if you came to me with a rheumatoid arthritis flare, I would prescribe steroids. But fibromyalgia is different and we have to address it differently.” By being clear and compassionate in making these statements, Dr. Kaplan believes rheumatologists and patients can more easily get onto the same page.

Among the non-pharmacologic interventions doctors can offer to patients with fibromyalgia include addressing psychological wellness, anxiety and sleep issues. Cognitive behavioral therapy, also known as CBT, is recommended as a first-line behavioral intervention for fibromyalgia in U.S. and international guidelines, with benefits observed across diverse patient populations.¹ Although patients may sometimes interpret the recommendation to engage in CBT treatment as a way of the doctor saying, “it’s all in your head,” there is evidence clinicians can point to showing the effectiveness of this therapy.

Because the availability of providers trained in CBT methodologies is limited in many cities and towns across the country, Dr. Kaplan made note of a smartphone application called Stanza that can provide the therapy through a digital interface.

Neuromodulation—including transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), transcranial random noise stimulation (tRNS) and transcutaneous vagus nerve stimulation (tVNS)—can also be used as a treatment for fibromyalgia, though further research is needed to refine protocols and confirm long-term benefits.

Dr. Kaplan ended his lecture cycling through a few frequently asked questions he receives: Does he test for small fiber neuropathy with a skin biopsy? (Not typically unless there is a co-occurring autoimmune disease like Sjogren’s.) Does he use low-dose naltrexone as a treatment? (Sometimes.) Where can patients go for additional resources? (He highly recommends painguide.com.)

Drug Therapies

The second speaker was Yvonne Lee, MD, the Helen Myers McLoraine Professor of Rheumatology at the Feinberg School of Medicine at Northwestern University in Chicago, and her task was to discuss pharmacologic therapies for pain. Similar to Dr. Kaplan, D. Lee teased apart nociplastic pain from nociceptive pain, which is pain that arises from actual or threatened damage to body tissue caused by activation of pain-sensing nerve fibers, and neuropathic pain, which is defined as pain caused by damage or dysfunction of the nervous system itself that leads to abnormal pain signaling.

Dr. Lee noted that suzetrigine, a Nav1.8 inhibitor, was approved by the Food and Drug Administration (FDA) in January 2025 as a new, non-opioid treatment for moderate to severe acute pain. The medication works by selectively inhibiting the Nav1.8 voltage-gated sodium channel, which is a significant factor in transmitting pain signals. Although patients may bring up the idea of this therapy after hearing about it in the news, Dr. Lee explained there is currently no data on how Nav1.8 inhibitors may work in rheumatic diseases, and she believes they are unlikely to help with nociplastic pain such as that seen with fibromyalgia.

Dr. Lee next discussed sublingual cyclobenzaprine (TNX-102 SL), which in August 2025 became the first FDA-approved treatment for fibromyalgia since milnacipran in 2009. Oral cyclobenzaprine has often been used off-label by clinicians to treat fibromyalgia, but the sublingual form is felt to have more rapid absorption and potentially improved pharmacokinetics compared to oral formulations. In two pivotal double-blind, placebo-controlled trials, sublingual cyclobenzaprine produced a statistically significant reduction in pain intensity scores versus placebo for patients with fibromyalgia, with 46–47% of patients achieving at least a 30% improvement in pain at 14 weeks.^2-3 These improvements are not consistently observed with oral cyclobenzaprine, which has shown only modest effects on sleep and no significant impact on pain or global function in fibromyalgia populations.⁴

Dr. Lee also discussed medications that are not prescribed exclusively for pain but nevertheless appear to have analgesic effects. Janus kinase (JAK) inhibitors are well known to rheumatologists who manage inflammatory arthritides, but it’s less commonly known that these medications may act directly or indirectly to decrease pain via multiple pathways, such as through the central nervous system (CNS), dorsal root ganglion and peripheral nerves at the joints. In one paper cited by Dr. Lee, the 60% of the effect of the JAK inhibitor baricitinib on pain seemed to occur via “non-inflammatory” pathways.⁵ Dr. Lee believes the future of pain management in the rheumatic diseases will rest on understanding these non-inflammatory pathways of pain modulation, personalizing pain management for patients (including by phenotyping pain as nociceptic versus nociplastic), using combination therapies (such as with an anti-inflammatory along with a central analgesic), and integrating behavioral interventions.

The session may have been about pain, but the audience left feeling relieved to have gained such newfound knowledge from the speakers. Much remains to be done to help patients who are suffering, but now it appears there is more hope to do so.

Jason Liebowitz, MD, FACR, is an assistant professor of medicine in the Division of Rheumatology at Columbia University Vagelos College of Physicians and Surgeons, New York.

References

1. Bernardy K, Klose P, Busch AJ, et al. Cognitive behavioural therapies for fibromyalgia. Cochrane Database Syst Rev. 2013 Sep 10;2013(9):CD009796.
2. Lederman S, Arnold LM, Vaughn B, et al. Efficacy and Safety of Sublingual Cyclobenzaprine for the Treatment of Fibromyalgia: Results From a Randomized, Double-Blind, Placebo-Controlled Trial. Arthritis Care Res (Hoboken). 2023 Nov;75(11):2359-2368.
3. Lederman S, Arnold LM, Vaughn B, et al. Pain Relief by Targeting Nonrestorative Sleep in Fibromyalgia: A Phase 3 Randomized Trial of Bedtime Sublingual Cyclobenzaprine. Pain Med. 2025 Jul 8:pnaf089.
4. Oldfield BJ, Gleeson B, Morford KL, et al. Long-Term Use of Muscle Relaxant Medications for Chronic Pain: A Systematic Review. JAMA Netw Open. 2024 Sep 3;7(9):e2434835.
5. Taylor PC, Lee YC, Fleischmann R, et al. Achieving Pain Control in Rheumatoid Arthritis with Baricitinib or Adalimumab Plus Methotrexate: Results from the RA-BEAM Trial. J Clin Med. 2019 Jun 12;8(6):831.