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Supraspinal and spinal cord opioid receptors are responsible for antinociception following intrathecal morphine injections

Published online by Cambridge University Press:  23 December 2004

C. S. Goodchild ,
R. Nadeson  and
E. Cohen
C. S. Goodchild
Affiliation:
Monash University Department of Anaesthesia, Monash Medical Centre, Clayton, Victoria, Australia
R. Nadeson
Affiliation:
Monash University Department of Anaesthesia, Monash Medical Centre, Clayton, Victoria, Australia
E. Cohen
Affiliation:
Monash University Department of Anaesthesia, Monash Medical Centre, Clayton, Victoria, Australia
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Abstract

Summary

Background and 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: β-funaltrexamine (μ), naltrindole (δ) and nor-binaltorphimine (κ).

Results: Intrathecal morphine caused dose-related antinociceptive effects that were reversed totally by naloxone. Intrathecal β-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 μ-opioid receptors in the spinal cord.

Keywords

ANALGESICS, opioidCENTRAL NERVOUS SYSTEM, SPINAL CORDINJECTIONS, spinalPAIN, measurementRECEPTORS, neurotransmitter
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 21 , Issue 3 , March 2004 , pp. 179 - 185
Copyright
2004 European Society of Anaesthesiology

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