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.
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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)
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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
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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)
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