Fibromyalgia, milnacipran and experimental pain modulation: study protocol for a double blind randomized controlled trial

Abstract

BackgroundThe prevalence of fibromyalgia increases worldwide and is characterized by widespread and chronic pain. Treatment is difficult and includes both drug and non-drug approaches. Milnacipran, an antidepressant, is used for fibromyalgia, with a possible beneficial effect on central pain modulation. Our hypothesis is that the efficacy of milnacipran in fibromyalgia depends on the performance of pain inhibitory controls.Methods/designA randomized, double blind, clinical trial (NCT01747044) with two parallel groups, in 48 women with fibromyalgia, is planned in the Clinical Pharmacology Center, University Hospital, Clermont-Ferrand, France. Conditioned pain modulation (estimated with thermal stimuli using a numeric pain rating scale), the primary endpoint measure, is evaluated before and one month after treatment with milnacipran or placebo. Secondary outcome measures include the predictability of pain descending pathways performance for milnacipran efficacy, tolerance and cognitive function. Data analysis is performed using mixed models; the tests are two-sided, with a type I error set at alpha = 0.05. Not only will this trial allow estimation of the beneficial effect of milnacipran on pain and on descending pain pathways but it will also evaluate whether the performance of this modulatory system could be predictive of its efficacy in alleviating pain.DiscussionThis method would allow clinicians to take a pro-active attitude by performing a rapid psychophysical test before starting milnacipran treatment and would avoid unnecessary prescription while preventing therapeutic failure in patients who often face this recurrent problem.Trial registrationClinicalTrials.gov NCT01747044.

An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens

“…As mentioned previously, the research output on this topic is increasing, and some authors have published clinical trials comparing serotonergic and estrogen medications with other therapeutic options. Although more research still needs to be conducted, there are promising results about the efficacy of SSRIs and SNRIs for the treatment of several painful conditions including, but not limited to IBS, fibromyalgia, neuropathic pain, and migraine [161,162,163]. However, although estrogens seem to also have a role in the modulation of acute pain due to the location of receptors in the membrane and cytoplasm, there is scant literature exploring the efficacy of hormonal treatment to decrease pain intensity in acute conditions.…”

Milnacipran poorly modulates pain in patients suffering from fibromyalgia: a randomized double-blind controlled study

“…Alteration in the central modulation of pain and diffuse noxious inhibitory controls has been demonstrated in FM patients 19 , 23 – 25 using an experimental psychophysics technique, conditioned pain modulation (CPM). 26 – 29 Dysfunction of neurotransmitters has also been described, 30 – 39 justifying the use of antidepressants in FM patients.…”

A case of fibromyalgia involving pain throughout the body treated with site-specific targeted pain control

“…The proposed mechanisms for fibromyalgia include failure of the descending pain modulatory system (La Cesa et al 2014 ; Macian et al 2015 ) and central sensitization (Fleming and Volcheck 2015 ; Staud et al 2001 ); however, its causes are not clear.…”