Abstract
Tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors are used to treat chronic pain, such as neuropathic pain. Why antidepressants are effective for treatment of neuropathic pain and the precise mechanisms underlying their effects, however, remain unclear. The inhibitory effects of these antidepressants for neuropathic pain manifest more quickly than their antidepressive effects, suggesting different modes of action. Recent studies of animal models of neuropathic pain revealed that noradrenaline is extremely important for the inhibition of neuropathic pain. First, increasing noradrenaline in the spinal cord by reuptake inhibition directly inhibits neuropathic pain through α2-adrenergic receptors. Second, increasing noradrenaline acts on the locus coeruleus and improves the function of an impaired descending noradrenergic inhibitory system. Serotonin and dopamine may reinforce the noradrenergic effects to inhibit neuropathic pain. The mechanisms of neuropathic pain inhibition by antidepressants based mainly on experimental findings from animal models of neuropathic pain are discussed in this review.
Highlights
Antidepressants were not originally designed to act as analgesics, they are reported to have analgesic effects for chronic pain
[29] Fluoxetine and paroxetine have weak inhibitory effects on noradrenaline transporters [30,31], and their effects to increase noradrenaline are likely indirect. These findings suggest that the increase in noradrenaline in the spinal cord plays a crucial role in the inhibitory effects of antidepressants on neuropathic pain
When the same experiment was carried out using animal models of neuropathic pain (SNL animals), the Noxious stimulation induced analgesia (NSIA) was no longer recognized six weeks after nerve injury, and the noradrenaline is not increased in the spinal cord [27,41,44]
Summary
Antidepressants were not originally designed to act as analgesics, they are reported to have analgesic effects for chronic pain. Antidepressants have virtually no antinociceptive effects, but are considered first-line drugs of choice for neuropathic pain [1,2,3,4] and treatment of fibromyalgia [5]. 2. Effects of Antidepressants on Neuropathic Pain Differ from Their Effects on Depression. Antidepressants, along with pregabalin/gabapentin (voltage-dependent calcium channels α2δ subunit ligands) are used as first-line drugs for treating neuropathic pain [1,2,3,4]. The effects of antidepressants on depression characteristically take approximately two to four weeks to be observed from the time the drug is first taken, whereas the analgesic effects on chronic pain manifest in as little as few days to one week [7]. The analgesic effects of antidepressants on chronic pain likely involve a mechanism different from that mediating their antidepressive effects
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
