Effects of a cannabinoid agonist on spinal nociceptive neurons in a rodent model of neuropathic pain.

Abstract

The effects of the synthetic cannabinoid WIN 55,212-2 on heat-evoked firing of spinal wide dynamic range (WDR) neurons were examined in a rodent model of neuropathic pain. Fifty-eight WDR neurons (1 cell/animal) were recorded from the ipsilateral spinal dorsal horns of rats with chronic constriction injury (CCI) and sham-operated controls. Relative to sham-operated controls, neurons recorded in CCI rats showed elevations in spontaneous firing, noxious heat-evoked responses, and afterdischarge firing as well as increases in receptive field size. WIN 55,212-2 (0.0625, 0.125, and 0.25 mg/kg, intravenous) dose-dependently suppressed heat-evoked activity and decreased the receptive field areas of dorsal horn WDR neurons in both nerve injured and control rats with a greater inhibition in CCI rats. At the dose of 0.125 mg/kg iv, WIN 55,212-2 reversed the hyperalgesia produced by nerve injury. The effect of intravenous administration of WIN 55,212-2 appears to be centrally mediated because administration of the drug directly to the ligated nerve did not suppress the heat-evoked neuronal activity in CCI rats. Pretreatment with the cannabinoid CB(1) receptor antagonists SR141716A or AM251, but not the CB(2) antagonist SR144528, blocked the effects. These results provide a neural basis for reports of potent suppression by cannabinoids of the abnormal sensory responses that result from nerve injury.

• Authors: Cheng Liu, J Michael Walker
• Journal: Journal of neurophysiology (J Neurophysiol) Vol. 96 Issue 6 Pg. 2984-94 (Dec 2006) ISSN: 0022-3077 [Print] United States
• PMID: 16943316 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Benzoxazines
• Camphanes
• Cannabinoid Receptor Agonists
• Cannabinoid Receptor Antagonists
• Morpholines
• Naphthalenes
• Piperidines
• Pyrazoles
• Receptor, Cannabinoid, CB1
• Receptor, Cannabinoid, CB2
• SR 144528
• AM 251
• (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
• Rimonabant

Topics

• Analgesics (pharmacology)
• Animals
• Behavior, Animal (drug effects, physiology)
• Benzoxazines
• Camphanes (pharmacology)
• Cannabinoid Receptor Agonists
• Cannabinoid Receptor Antagonists
• Dose-Response Relationship, Drug
• Electrophysiology
• Hot Temperature
• Hyperalgesia (drug therapy, physiopathology, psychology)
• In Vitro Techniques
• Morpholines (pharmacology)
• Naphthalenes (pharmacology)
• Neurons (drug effects)
• Nociceptors (drug effects)
• Pain (drug therapy, etiology, physiopathology)
• Peripheral Nervous System Diseases (complications, physiopathology)
• Piperidines (pharmacology)
• Posterior Horn Cells (physiology)
• Pyrazoles (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptor, Cannabinoid, CB1 (agonists, antagonists & inhibitors, drug effects)
• Receptor, Cannabinoid, CB2 (agonists, antagonists & inhibitors, drug effects)
• Rimonabant
• Spinal Cord (cytology, drug effects, physiopathology)