Analgesic Mechanisms of Antidepressants for Neuropathic Pain

Int J Mol Sci. 2017 Nov 21;18(11):2483. doi: 10.3390/ijms18112483.


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.

Keywords: 5-HT; allodynia; dopamine; hyperalgesia; locus coeruleus; noradrenaline; rats; spinal cord; spinal nerve ligation; α2-adrenergic receptors.

Publication types

  • Review

MeSH terms

  • Analgesics / pharmacology*
  • Analgesics / therapeutic use*
  • Animals
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use*
  • Depression / drug therapy
  • Depression / etiology
  • Depression / metabolism
  • Dopamine / metabolism
  • Humans
  • Locus Coeruleus / drug effects
  • Locus Coeruleus / metabolism
  • Neuralgia / drug therapy*
  • Neuralgia / etiology
  • Neuralgia / metabolism
  • Norepinephrine / metabolism
  • Norepinephrine / pharmacology
  • Serotonin / metabolism
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism


  • Analgesics
  • Antidepressive Agents
  • Serotonin
  • Dopamine
  • Norepinephrine