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Author(s): Jose R. Rodriguez,MD, Charles Brock MD, Emil Gaitour MDAffiliations: Division of Interventional Pain Management , Department of Neurology James A. Haley VA Hospital University of South Florida, Collage of MedicineView poster »

Abstract: Methods Case of a 62-year-old Caucasian woman with a history of over 27 years of fatigue, widespread pain, and sleep disturbances. Patient also had co-morbidities of migraines, depression, cervical and lumbosacral spondylosis with cervical arthroplasty. She was diagnosed with fibromyalgia in 1991. Since then she tried different treatment modalities without significant pain relief. Initial pharmacological regimen included: ibuprofen, methocarbamol and Fluoxetine. This regimen did not provide significant pain relief with pain scores up to 9 out of 10 with muscle tenderness in multiple points on her body. During the course of seven years the patient tried medications such as Lyrica, Savella, Cymbalta (these are three medications FDA-approved to treat fibromyalgia). She also tried gabapentin, Tizanidine, Meloxicam and Salsalate without significant relief. Though she had been exposed to a varied treatment combination patient reported her lowest level of pain at 6 out of 10, with a daily average of 9. Suboptimal relief of fibromyalgia pain was a source of frustration and concern for the patient. After discussing treatment options, Methadone 5mg twice a day by mouth was added to her current regimen of Fluoxetine 20mg and Gabapentin 3600mg daily.

Results Several weeks after starting Methadone 5mg twice a day patient reported that her pain level was reduced to a daily average of 4 out of 10. Her mood and sleep were also improved, and her adherence to the treatment plan was significantly better. Her pain regimen has remained unchanged since initiation of methadone.

Conclusions Methadone use, though is controversial, has been used successfully to treat chronic pain and in FMS as seen in our patient. Patients with FMS exhibit an abnormal reaction to stimuli that normally would not cause pain. The hypothesized mechanism of chronic pain in FMS patient is central sensitization of second order neurons secondary to abnormal elevated levels of pro-inflammatory cytokines which have been demonstrated to have an effect on neural excitability and enable pain transmission and alteration of pain modulatory pathway. Patients with FMS also present with peripheral tissue abnormalities that include increased levels of Substance P in muscle tissue and increased Interleukin in cutaneous tissue, among other perfusion abnormalities. These changes are associated to peripheral sensitization of NMDA receptors that are present in the skin. Immediate central sensitization depends on mechanisms at the dorsal horn receptors, including NMDA receptors. This mechanism includes hyperexcitability of spinal dorsal-horn neurons that communicate nociceptive messages to the brain. Methadone is µ receptor agonist with low affinity and a central NMDA receptor antagonist .It is possibly a peripheral NMDA receptor antagonist as well. NMDA receptor activation is a critical element of central sensitization and by blocking this receptor peripherally and centrally, it may decrease tertiary sensitization at the level of the thalamus providing an additional non-opioid mechanism to decrease pain in FMS. Methadone also has other essential properties that make it an attractive alternative to treat chronic pain including: long half-life, good oral bioavailability, delayed withdrawal, low-cost and convenient dosing.

Methadone is an effective option to conventional opioids for chronic pain management when used in a controlled environment with close monitoring and cautious dose initiation and titration. Further research is necessary to assess to the effectiveness of this drug treating FMS pain either as primary or adjuvant therapy. Summary: A case highlights the successful use of methadone in a patient with Fibromyalgia syndrome (FMS) who after trying a variety of drugs, including the ones recommended established guidelines, did not reach adequate pain relief. Methadone not only provided a better pain control but also a significantly better adherence compared to a more traditional approach.References: 1. Rogers SJ, Husinger-Norris DM. Fibromyalgia. Neuro and Psych care 2015: 5-14. 2. Borchers AT, Gershwin, ME. Fribromyalgia: A critical and comprehensive review. Clinic Rev Allerg Immunol 2015; 48: 100-151. 3. Liu Y, Qian C, Yang M. Treatment patterns associated with ACR-recommended medications in the management of Fibromyalgia in the United States. J Managed Care and Spec Pharm 2016; 22 (3): 263-271. 4. Arnold LM, Clauw DJ, McCarberg BH. Improving the recognition and diagnosis of Fibromyalgia. Mayo Clin Proc 2011: 86(5): 457-464. 5. Talotta R, Bazzichi L, Di Franco M, Casale R, Batticciotto A, Gerardi MC, Sarzi-Puttini P. One year in review 2017: Fibromyalgia. Clin Exp Rheumatol 2017; 105(3): 6-12. 6. Mease PJ, Dundon K, Sarzi-Puttini P. Pharmacotherapy of Fibromyalgia. Best Pract Res Clin Rheumatol 2011; 25(2): 285-297. 7. Calandre EP, Rico-Villademoros F, Rodriguez-Lopez CM. Monotherapy or combination therapy for fibromyalgia treatment? Curr Rheumatl RepReport abuse »