Effects of noradrenergic and serotonergic antidepressants on chronic low back pain intensity

Abstract

To understand the relative efficacy of noradrenergic and serotonergic antidepressants as analgesics in chronic back pain without depression, we conducted a randomized, double-blind, placebo-control head-to-head comparison of maprotiline (a norepinephrine reuptake blocker) and paroxetine (a serotonin reuptake blocker) in 103 patients with chronic low back pain. Of these 74 completed the trial; of the 29 who did not complete, 19 were withdrawn because of adverse effects. The intervention consisted of an 8-week course of maprotiline (up to 150 mg daily) or paroxetine (up to 30 mg daily) or an active placebo, diphenhydramine hydrochloride (up to 37.5 mg daily). Patients were excluded for current major depression. Reduction in pain intensity (Descriptor Differential Scale scores) was significantly greater for study completers randomized to maprotiline compared to placebo (P=0.023), and to paroxetine (P=0.013), with a reduction of pain by 45% compared to 27% on placebo and 26% on paroxetine. These results suggest that at standard dosages noradrenergic agents may provide more effective analgesia in back pain than do selective serotonergic reuptake inhibitors.

Plasma levels of beta-endorphin and serotonin in response to specific spinal based exercises

“…Biosynthesis of serotonin in the human body involves hydroxylation of tryptophan (essential amino acid) by tryptophan hydroxylase to produce 5-hydroxytryptophan (5-HTP) and decarboxylation of 5-HTP by aromatic-L-amino acid decarboxylase to produce serotonin (Kema et al 2000). It has been established that there are two pools of tryptophan in the blood tissue; one that is bound to platelets and the other that is free (Atkinson et al 1999). Thus, it could be said that serotonin synthesis is dependent on free tryptophan availability.…”

“…Consequently, processes that influence equilibrium between free tryptophan and platelets bound tryptophan will affect serotonin synthesis rate. The efflux of serotonin from platelets is increased by many factors including raised levels of adrenaline as occur during exercise and many other stress situations (Atkinson et al 1999).…”

“…Although the exact mechanism and pathways involved in both actions still remain unclear (Atkinson 1999). It could then be assumed that the analgesic ability of serotonin is related to alleviation of depression, which can often accompany chronic pain.…”

The Effect of Agomelatine on the Nociceptive System

“…It is known that some antidepressant drugs also have an antinociceptive effect; therefore they can be used for the treatment of painful conditions especially accompanied by depression 20,33,35 . Agomelatine is an analogue of melatonin (MT), which is an agonist of MT 1 and MT 2 16,36 .…”

Acute and subchronic effects of amitriptyline 25mg on actual driving in chronic neuropathic pain patients

“…Max, 1994;McQuay et al, 1996;Kingerly, 1997;Dworkin et al, 2003), although amitriptyline is not FDA approved for the treatment of neuropathic pain. Amitriptyline is thought to exert its analgesic effects through inhibition of both norepinephrine and serotonin neurotransmitter reuptake (Atkinson et al, 1999). The analgesic effect of amitriptyline appears to be independent of its antidepressant effect (McQuay et al, 1996).…”