Attenuation of c-Fos expression in the rat lumbosacral spinal cord by morphine or tramadol following noxious colorectal distention.
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.
Traub
R J
RJ
Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242, USA.
Stitt
S
S
Gebhart
G F
GF
D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003106:Colon / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000502:physiology*; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010146:Pain / Q000378:metabolism*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D014147:Tramadol / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D014147:Tramadol; D009020:Morphine