Focus on pain mechanisms and pharmacotherapy in the treatment of fibromyalgia syndrome.

OBJECTIVE: To critically evaluate the role of several notable 'pain pathways' in the fibromyalgia syndrome (FMS). METHODS: PubMed provided the data base for peer-reviewed basic and clinical science studies on musculoskele-tal and neuropathic pain mechanisms with a principal emphasis on critically appraising papers from 2002 to the present. RESULTS: FMS pharmacotherapy is more prevalent in clinical practice as our understanding of the cellular, molecular and pathophysiologic mechanisms contributing to widespread musculoskeletal and neuropathic pain has emerged. Thus, several 'pain pathways' including high-voltage activated Ca2+ channels and the K(v)1 family of K+ channels ion channels appear related to the efficacy of pregabalin and amitryptyline, respectively, in FMS. Additionally, serotonergic and serotonergic/norepinephrine receptor-mediated mechanisms may explain the reported pharmacologic efficacy in FMS of mirtazapine, duloxetine and milnacipran. By contrast, the decreased level of micro-opioid receptors in the CNS of FMS patients suggests a mechanism as to why opioid therapy should be avoided. However, increased peripheral benzodiazepine receptors on monocytes from FMS patients suggested an explanation for the reported efficacy of olanzapine in FMS. CONCLUSION: Pregabalin was the first drug approved by the FDA for the treatment of FMS-related pain. Drugs that have been assessed for their potential use in FMS pharmacotherapy include gabapentin and tricylic antidepressants. These drugs appear to target specific Ca2+ or K+ ion channels notable for their involvement in mediating neuropathic pain. Serotonin and norepinephrine reuptake inhibitors including, mirtazapine, duloxetine and milnacipran appear to be more efficacious in FMS than selective serotonin reuptake inhibitors. Milnacipran became the second FDA-approved drug for FMS.