Antihyperalgesic effect of duloxetine and amitriptyline in rats after peripheral nerve injury: Influence of descending noradrenergic plasticity

Neurosci Lett. 2015 Aug 18:602:62-7. doi: 10.1016/j.neulet.2015.06.041. Epub 2015 Jun 29.


Antidepressants such as serotonin-noradrenaline reuptake inhibitors (SNRIs) and tricyclic antidepressants (TCAs) are frequently used for the management of neuropathic pain. Noradrenaline (NA) and serotonin (5-HT) increase in the spinal cord by reuptake inhibition is considered to be main mechanism of the therapeutic effect of antidepressants in neuropathic pain. In the present study, we examined the analgesic effects of duloxetine (SNRI) and amitriptyline (TCA) in a rat model of neuropathic pain induced by spinal nerve ligation (SNL). Intraperitoneal administration of duloxetine and amitriptyline dose-dependently (3,10 and 30 mg/kg) suppressed hyperalgesia induced by SNL. In vivo microdialysis in the lumbar spinal dorsal horn revealed that NA and 5-HT concentrations increased after intraperitoneal administration of duloxetine and amitriptyline (10 mg/kg, respectively). We further determined NA and 5-HT contents in homogenized samples from the ipsilateral dorsal spinal cord after SNL. Although the NA content in SNL rats 2 weeks after ligation was higher than that in SNL rats 4 weeks after ligation, the analgesic efficacy of duloxetine and amitriptyline was similar between two groups. The present study suggests that NA/5-HT increase in the spinal cord is crucial in the antihyperalgesic effect of duloxetine and amitriptyline. The plastic change of the descending noradrenergic system does not obviously affect the analgesic efficacy of duloxetine and amitriptyline.

Keywords: Amitriptyline; Antidepressants; Duloxetine; Neuropathic pain; Noradrenaline; Serotonin; Spinal cord.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amitriptyline / therapeutic use*
  • Analgesics / therapeutic use*
  • Animals
  • Duloxetine Hydrochloride
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / physiopathology
  • Lumbosacral Region
  • Male
  • Neuronal Plasticity*
  • Norepinephrine / metabolism*
  • Rats, Sprague-Dawley
  • Serotonin / metabolism
  • Spinal Cord Dorsal Horn / metabolism
  • Spinal Nerves / injuries*
  • Thiophenes / therapeutic use*
  • Time Factors


  • Analgesics
  • Thiophenes
  • Amitriptyline
  • Serotonin
  • Duloxetine Hydrochloride
  • Norepinephrine