Supraspinal and spinal cord opioid receptors are responsible for antinociception following intrathecal morphine injections.
OBJECTIVE
The clinical practice of spinal morphine administration for pain relief is based on observations in animals that opioid receptors exist in the spinal cord and intrathecal injections of opioids in those species (mostly rats) lead to antinociceptive effects. Clinicians are well aware that administration of spinal opioids is associated with side-effects, such as nausea and respiratory depression, that indicate supraspinal spread of the drug administered. Those observations call into question how much of the observed pain relief is due to action of the drug in the brain. This study investigated the spinal cord actions of morphine given intrathecally to rats in a model that allows investigation of drug-receptor interaction at the spinal cord level. Experiments were performed on male Wistar rats with chronically implanted lumbar subarachnoid catheters.


METHODS
Nociceptive thresholds were measured in rats given morphine intrathecally alone and in combination with intrathecal injections of selective opioid receptor antagonists: beta-funaltrexamine (mu), naltrindole (delta) and nor-binaltorphimine (kappa).


RESULTS
Intrathecal morphine caused dose-related antinociceptive effects that were reversed totally by naloxone. Intrathecal beta-funaltrexamine and naltrindole did not reverse the effects of intrathecal morphine. However, intrathecal nor-binaltorphimine did reverse the electrical current threshold effects of morphine but not tail flick latency.


CONCLUSIONS
Antinociception following intrathecal morphine involves spinal and supraspinal opioid receptors. The tail flick effect described in rat experiments involves actions at opioid receptors in the brain that override any action that may be caused by combination of morphine with mu-opioid receptors in the spinal cord.
Goodchild
C S
CS
Monash University Department of Anaesthesia, Monash Medical Centre, Clayton, Victoria, Australia. colin.goodchild@med.monash.edu.au
Nadeson
R
R
Cohen
E
E
D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008297:Male; D023421:Models, Animal; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects*; D013623:Tail / Q000502:physiology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; C055382:naltrindole