Regulation of Pain in Fibromyalgia by Selective Serotonin and Serotonin Norepinephrine Reuptake Inhibition
Charles J Malemud*
Department of Medicine, Division of Rheumatic Diseases, Case Western Reserve University, School of Medicine, and University Hospitals Case Medical Center, Cleveland, Ohio USA
- *Corresponding Author:
- Charles J Malemud
Department of Medicine, Division of Rheumatic Diseases
University Hospitals Case Medical Center
Foley Medical Building, 2061 Cornell Road
Room 207, Cleveland, OH 44106-5076 USA
Tel: (216) 536-1945
Fax: (216) 844-2288
E-mail: [email protected]
Received Date: May 02, 2013; Accepted Date: July 20, 2013; Published Date: July 25, 2013
Citation: Malemud CJ (2013) Regulation of Pain in Fibromyalgia by Selective Serotonin and Serotonin Norepinephrine Reuptake Inhibition. Int J Phys Med Rehabil 1:144. doi: 10.4172/2329-9096.1000144
Copyright: © 2013 Malemud CJ. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Fibromyalgia is a chronic pain processing disorder primarily affecting the musculoskeletal system. Fibromyalgia is often accompanied by chronic fatigue, dyscognition and altered sleep architecture. One mechanism widely recognized as contributing to chronic pain in fibromyalgia involves musculoskeletal tenderness in response to innocuous mechanical stimuli also known as allodynia. However, the recently performed re-analysis of the clinical criteria for the diagnosis of fibromyalgia proposed that physicians should also take into account a patient’s overall symptoms deemphasizing the tender point count. It is generally agreed that the cellular basis for the chronic musculoskeletal pain of fibromyalgia involves abnormalities in ascending and descending pain pathways resulting from heightened central nervous system sensitization. Of note, the results of studies employing animal models of chronic pain substantiate such a mechanism. Importantly, the co-morbidities characteristic of fibromyalgia patients also suggests a genetic component presumably involving biogenic amines and single nucleotide polymorphisms in the serotonin transporter protein and dopamine transporter and receptor genes. By all indications the 5-hydroxytryptamine/5-hydroxytryptamine receptor pathway appears to be an appropriate target for therapeutic intervention. Indeed, selective-serotonin reuptake inhibitors and serotonin/norepinephrine reuptake inhibition have now been added to antidepressant medicines and pregabalin as clinically efficacious drugs for fibromyalgia. It is now thought that antidepressants such as amitryptiline and pregabalin act via high-voltage activated Ca2+ channels and the Kv1 family of K+ channels and/or by modifying defective serotonergic circuitry exemplified by abnormalities in serotonergic receptor-mediated events. Selectiveserotonin and serotonin/norepinephrine reuptake inhibitors such as duloxetine and milnacipran, respectively, act through a G-protein-coupled mechanism involving the 5-hydroxytryptamine/5-hydroxytryptamine-(2A) receptor which leads to activation of cyclic AMP-dependent protein kinase A and Ca2+/calmodulin kinase IV. However, more recent evidence indicated that this drug class also activates Janus kinase-3, extracellular signal-regulated kinase 1/2 and the Src/Phosphatidylinositide-3-kinase (PI3K)/Akt/Glycogen Synthase Kinase-3/mammalian target of rapamycin signaling pathway.