Role and rationale for the use of milnacipran in the management of fibromyalgia

Abstract

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread musculoskeletal pain which is often accompanied by multiple other symptoms, including fatigue, sleep disturbances, decreased physical functioning, and dyscognition. Due to these multiple symptoms, as well as high rates of comorbidity with other related disorders, patients with FM often report a reduced quality of life. Although the pathophysiology of FM is not completely understood, patients with FM experience pain differently from the general population, most likely due to dysfunctional pain processing in the central nervous system leading to both hyperalgesia and allodynia. In many patients with FM, this aberrant pain processing, or central sensitization, appears to involve decreased pain inhibition within the spinal tract, which is mediated by descending pathways that utilize serotonin, norepinephrine, and other neurotransmitters. The reduced serotonin and norepinephrine levels observed in patients with FM suggest that medications which increase the levels of these neurotransmitters, such as serotonin and norepinephrine reuptake inhibitors (SNRIs), may have clinically beneficial effects in FM and other chronic pain conditions. Milnacipran is an SNRI that has been approved for the management of FM. In clinical trials, treatment with milnacipran for up to 1 year has been found to improve the pain and other symptoms of FM. Because FM is characterized by multiple symptoms that all contribute to the decreased quality of life and ability to function, the milnacipran pivotal trials implemented responder analyses. These utilized a single composite endpoint to identify the proportion of patients who reported simultaneous and clinically significant improvements in pain, global disease status, and physical function. Other domains assessed during the milnacipran trials include fatigue, multidimensional functioning, mood, sleep quality, and patient-reported dyscognition. This review article provides information intended to help clinicians make informed decisions about the use of milnacipran in the clinical management of patients with FM. It draws primarily on results from 2 of the pivotal clinical trials that formed the basis of approval of milnacipran in the United States by the Food and Drug Administration.

The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

“… 51 , 114 , 150 , 176 , 192 Emerging evidence suggests that dysfunctional pain states, such as rheumatoid arthritis, osteoarthritis, visceral pain hypersensitivity syndromes, fibromyalgia, inflammatory bowel syndrome, neuropathic pain, and headaches, including migraine headache, may be caused in part by a deficient endogenous pain inhibitory system that allows the development of central sensitization. 1 , 33 , 96 , 108 , 169 , 192 …”

Acupuncture Improves Sleep Conditions of Minipigs Representing Diurnal Animals through an Anatomically Similar Point to the Acupoint (GV20) Effective for Humans

“…Pharmacological drugs involved in serotonin and melatonin metabolism have been applied for people with sleep disturbances [ 5 , 6 ]; however, the number of people with sleep disturbances has not tended to decrease. At present, not only pharmacological drugs but also alternative medicines are administered [ 7 ].…”