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.
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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.”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [47]
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Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside
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- Authors
- Liu, C., & Walker, J. M.
- Affiliations
- Indiana University Bloomington (US)
- ORCID
- Liu, Cheng
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- 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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