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Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats.
Eur J Neurosci. 2000 Jun; 12(6):2079-86.EJ

Abstract

The analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of noninflamed and carrageenin-inflamed rats was studied with in vitro autoradiography of guanylyl 5'-[gamma-[35S]thio]triphosphate ([35S]GTPgammaS) binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300-800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin-inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTPgammaS binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTPgammaS binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C-fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G-protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states.

Authors+Show Affiliations

School of Biomedical Sciences, E Floor Medical School, University of Nottingham, Queen's Medical Centre, Nottingham, NG72UH, United Kingdom.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10886347

Citation

Drew, L J., et al. "Activation of Spinal Cannabinoid 1 Receptors Inhibits C-fibre Driven Hyperexcitable Neuronal Responses and Increases [35S]GTPgammaS Binding in the Dorsal Horn of the Spinal Cord of Noninflamed and Inflamed Rats." The European Journal of Neuroscience, vol. 12, no. 6, 2000, pp. 2079-86.
Drew LJ, Harris J, Millns PJ, et al. Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats. Eur J Neurosci. 2000;12(6):2079-86.
Drew, L. J., Harris, J., Millns, P. J., Kendall, D. A., & Chapman, V. (2000). Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats. The European Journal of Neuroscience, 12(6), 2079-86.
Drew LJ, et al. Activation of Spinal Cannabinoid 1 Receptors Inhibits C-fibre Driven Hyperexcitable Neuronal Responses and Increases [35S]GTPgammaS Binding in the Dorsal Horn of the Spinal Cord of Noninflamed and Inflamed Rats. Eur J Neurosci. 2000;12(6):2079-86. PubMed PMID: 10886347.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats. AU - Drew,L J, AU - Harris,J, AU - Millns,P J, AU - Kendall,D A, AU - Chapman,V, PY - 2000/7/11/pubmed PY - 2000/8/19/medline PY - 2000/7/11/entrez SP - 2079 EP - 86 JF - The European journal of neuroscience JO - Eur J Neurosci VL - 12 IS - 6 N2 - The analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of noninflamed and carrageenin-inflamed rats was studied with in vitro autoradiography of guanylyl 5'-[gamma-[35S]thio]triphosphate ([35S]GTPgammaS) binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300-800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin-inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTPgammaS binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTPgammaS binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C-fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G-protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states. SN - 0953-816X UR - https://www.unboundmedicine.com/medline/citation/10886347/Activation_of_spinal_cannabinoid_1_receptors_inhibits_C_fibre_driven_hyperexcitable_neuronal_responses_and_increases_[35S]GTPgammaS_binding_in_the_dorsal_horn_of_the_spinal_cord_of_noninflamed_and_inflamed_rats_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0953-816X&date=2000&volume=12&issue=6&spage=2079 DB - PRIME DP - Unbound Medicine ER -