Cited by 37Pain Mechanisms and TreatmentsCannabis and Cannabinoid ResearchPain Management and Treatment

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

Liu, Cheng, Walker, J. Michael·2006·Journal of Neurophysiology

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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Registry

Crossref · 10.1152/jn.00498.2006

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  • WIN55,212-2 dose-dependently inhibits windup and CCI-induced increases in spontaneous firing of spinal wide dynamic range neurons through a CB1-dependent mechanism.

    “A neurophysiological basis for these findings is derived from the observation that WIN55,212-2 (i.v.) dose-dependently inhibits windup46 as well as CCI-induced increases in spontaneous firing47 of spinal wide dynamic range (WDR) neurons through a CB1-dependent mechanism.”

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Authors
Liu, C., & Walker, J. M.
Affiliations
Indiana University Bloomington (US)
Venue
Journal of Neurophysiology
Published
2006-12
Volume
96
Issue
6
Pages
2984-2994
ISSN
  • 0022-3077 (ISSN-L)
  • 1522-1598
OpenAlex
W2073968978
Cited by
37
References
83
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2021: 1 · 2018: 2 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 5 · 2012: 4
FWCI
2.21
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neurophysiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (1f32da016825-01)
  • National Institute on Drug Abuse (DA 16825, DA 018224, R01DA018224)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
  • Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Keywords
WIN 55,212-2, cannabinoids, neuropathic pain, chronic constriction injury, spinal nociceptive neurons, wide dynamic range neurons, receptive field size, afterdischarge, hyperalgesia, CB1 receptor, CB2 receptor, dorsal horn
MeSH terms
Rimonabant, Analgesics, Animals, Behavior, Animal, Camphanes, Dose-Response Relationship, Drug, Electrophysiology, Hot Temperature, Hyperalgesia, Morpholines, Naphthalenes, Neurons, Nociceptors, Pain, Peripheral Nervous System Diseases, Piperidines, Pyrazoles, Spinal Cord, Rats, Sprague-Dawley, Posterior Horn Cells, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Benzoxazines, Rats, Cannabinoid Receptor Agonists, Cannabinoid Receptor Antagonists, In Vitro Techniques

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