Interaction between the spinal melanocortin and opioid systems in a rat model of neuropathic pain.

Abstract

BACKGROUND:

The authors recently demonstrated that administration of the melanocortin-4 receptor antagonist SHU9119 decreased neuropathic pain symptoms in rats with a sciatic chronic constriction injury. The authors hypothesised that there is a balance between tonic pronociceptive effects of the spinal melanocortin system and tonic antinociceptive effects of the spinal opioid system. Therefore, they investigated a possible interaction between these two systems and tested whether opioid effectiveness could be increased through modulation of the spinal melanocortin system activity.

METHODS:

In chronic constriction injury rats, melanocortin and opioid receptor ligands were administered through a lumbar spinal catheter, and their effects on mechanical allodynia were assessed by von Frey probing.

RESULTS:

Naloxone (10-100 microg) dose-dependently increased allodynia (percent of maximum possible effect of -67 +/- 9%), which is in agreement with a tonic antinociceptive effect of the opioid system. SHU9119 decreased allodynia (percent of maximum possible effect of 60 +/- 13%), and this effect could be blocked by a low dose of naloxone (0.1 microg), which by itself had no effect on withdrawal thresholds. Morphine (1-10 microg) dose-dependently decreased allodynia (percent of maximum possible effect of 73 +/- 14% with the highest dose tested). When 0.5 microg SHU9119 (percent of maximum possible effect of 47 +/- 14%) was given 15 min before morphine, there was an additive antiallodynic effect of both compounds.

CONCLUSIONS:

Together, these data confirm that there is an interaction between the spinal melanocortin and opioid systems and that combined treatment with melanocortin-4 receptor antagonists and opioids might possibly contribute to the treatment of neuropathic pain.

• Authors: Dorien H Vrinten, Willem Hendrik Gispen, Cor J Kalkman, Roger A H Adan
• Journal: Anesthesiology (Anesthesiology) Vol. 99 Issue 2 Pg. 449-54 (Aug 2003) ISSN: 0003-3022 [Print] United States
• PMID: 12883419 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics, Opioid
• Endorphins
• Narcotic Antagonists
• Receptor, Melanocortin, Type 4
• Receptors, Corticotropin
• alpha-MSH (4-10)amide, Ac-Nle(4)-cyclo(Asp(5)-Phe(7)-Lys(10))-
• SHU 9119
• Naloxone
• alpha-MSH
• Morphine
• Melanocyte-Stimulating Hormones

Topics

• Analgesics, Opioid (pharmacology)
• Animals
• Drug Interactions
• Endorphins (physiology)
• Male
• Melanocyte-Stimulating Hormones (metabolism, pharmacology)
• Morphine (pharmacology)
• Naloxone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Pain (physiopathology)
• Physical Stimulation
• Rats
• Rats, Wistar
• Receptor, Melanocortin, Type 4
• Receptors, Corticotropin (antagonists & inhibitors)
• Sensory Thresholds (physiology)
• Spinal Cord (metabolism)
• alpha-MSH (analogs & derivatives, pharmacology)