Attenuation of c-Fos expression in the rat lumbosacral spinal cord by morphine or tramadol following noxious colorectal distention

Brain Res. 1995 Dec 1;701(1-2):175-82. doi: 10.1016/0006-8993(95)00990-5.


We have previously reported that repetitive, noxious colorectal distention (CRD) induces c-Fos in the lumbosacral spinal cord. This study examined the effects of the analgesics morphine and tramadol on c-Fos expression resulting from noxious CRD in the rat. Pre-treatment (30 min or 1 min, i.v.) with morphine (1.25 mg/kg-5.0 mg/kg) or tramadol (1 mg/kg-20 mg/kg) dose-dependently attenuated c-Fos expression to CRD in all areas of the L6-S1 spinal gray matter. The highest dose of morphine was equipotent to the highest dose of tramadol. Repetitive dosing (1/4 of the greatest dose every 30 min) was as effective as a single bolus dose for both drugs. The visceromotor response to CRD was dose-dependently attenuated by tramadol and was reversed by naloxone. However, the dose of tramadol that eliminated the visceromotor response (7% of control) reduced the c-Fos expression to 47% of control. These results demonstrate that these two analgesics attenuate immediate-early gene expression and the visceromotor response to a noxious visceral stimulus and suggest that complete attenuation of c-Fos expression is not necessary for these compounds to produce analgesia to a noxious visceral stimulus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Analgesics, Opioid / metabolism*
  • Analgesics, Opioid / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Colon / physiology
  • Dose-Response Relationship, Drug
  • Electromyography / drug effects
  • Gene Expression / drug effects*
  • Genes, fos / physiology*
  • Male
  • Morphine / antagonists & inhibitors
  • Morphine / pharmacology*
  • Naloxone / pharmacology
  • Narcotic Antagonists / pharmacology
  • Pain / metabolism*
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Rectum / physiology
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism*
  • Tramadol / pharmacology*


  • Analgesics, Opioid
  • Narcotic Antagonists
  • Naloxone
  • Tramadol
  • Morphine