Cannabinoid CB2 receptor activation inhibits mechanically evoked responses of wide dynamic range dorsal horn neurons in naïve rats and in rat models of inflammatory and neuropathic pain
Abstract
Peripheral cannabinoid 2 receptors (CB2 receptors) modulate immune responses and attenuate nociceptive behaviour in models of acute and persistent pain. The aim of the present study was to investigate whether peripheral CB2 receptors modulate spinal processing of innocuous and noxious responses and to determine whether there are altered roles of CB2 receptors in models of persistent pain. Effects of local administration of the CB2 receptor agonist JWH-133 (5 and 15 microg/50 microL) on mechanically evoked responses of spinal wide dynamic range (WDR) neurons in noninflamed rats, rats with carrageenan-induced hindpaw inflammation, sham operated rats and spinal nerve-ligated (SNL) rats were determined in anaesthetized rats in vivo. Mechanical stimulation (von Frey filaments, 6-80 g) of the peripheral receptive field evoked firing of WDR neurons. Mechanically evoked responses of WDR neurons were similar in noninflamed, carrageenan-inflamed, sham-operated and SNL rats. Intraplantar injection of JWH-133 (15 microg), but not vehicle, significantly (P < 0.05) inhibited innocuous and noxious mechanically evoked responses of WDR neurons in all four groups of rats. In many cases the selective CB2 receptor antagonist, SR144528 (10 microg/50 microL), attenuated the inhibitory effects of JWH-133 (15 microg) on mechanically evoked WDR neuronal responses. The CB1 receptor antagonist, SR141716A, did not attenuate the inhibitory effects of JWH-133 on these responses. Intraplantar preadministration of JWH-133 also inhibited (P < 0.05) carrageenan-induced expansion of peripheral receptive fields of WDR dorsal horn neurons. This study demonstrates that activation of peripheral CB2 receptors attenuates both innocuous- and noxious-evoked responses of WDR neurons in models of acute, inflammatory and neuropathic pain.
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JWH133 attenuates mechanically-evoked responses of wide dynamic range neurons in both naive and spinal nerve ligated rats.
“The structurally distinct CB2-specific agonist, JWH133, also attenuates mechanically-evoked responses of WDR neurons in both naive and spinal nerve ligated rats.86”
From Cannabinoids as Pharmacotherapies for Neuropathic Pain: From the Bench to the Bedside (2009) · cites this paper as [86]
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- Authors
- Elmes, S. J. R., Jhaveri, M. D., Smart, D., Kendall, D. A., & Chapman, V.
- Affiliations
- University of Nottingham (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- Corresponding author
- Chapman, Victoria
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2004-10-04
- Volume
- 20
- Issue
- 9
- Pages
- 2311-2320
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1542482240
- Cited by
- 160
- References
- 51
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 3 · 2022: 2 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 9 · 2016: 3 · 2015: 4 · 2014: 7 · 2013: 8 · 2012: 8
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- University of Nottingham
- 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
- CB2 receptor, JWH-133, SR144528, SR141716A, wide dynamic range neurons, dorsal horn, mechanical nociception, inflammatory pain, neuropathic pain, spinal nerve ligation, carrageenan-induced inflammation, CB1 receptor, nociceptive processing
- MeSH terms
- Rimonabant, Action Potentials, Animals, Camphanes, Cannabinoids, Carrageenan, Disease Models, Animal, Inflammation, Ligation, Male, Neural Inhibition, Neuralgia, Nociceptors, Peripheral Nervous System Diseases, Physical Stimulation, Piperidines, Pyrazoles, Reaction Time, Sensory Receptor Cells, Spinal Nerves, Rats, Sprague-Dawley, Posterior Horn Cells, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Rats
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