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Dynorphin-independent spinal cannabinoid antinociception.
Pain. 2002 Dec; 100(3):243-248.PAIN

Abstract

Spinal antinociception produced by delta 9-tetrahydro-cannabinol (Delta(9)-THC) and other cannabinoid agonists has been suggested to be mediated by the release of dynorphin acting at the kappa opioid receptor. Alternatively, as cannabinoid receptors are distributed appropriately in the pain transmission pathway, cannabinoid agonists might act directly at the spinal level to inhibit nociception, without requiring dynorphin release. Here, these possibilities were explored using mice with a deletion of the gene encoding prodynorphin. Antinociceptive dose-response curves were constructed for spinal Delta(9)-THC and WIN 55,212-2 in prodynorphin knock-out mice and in wild-type littermates. WIN 55,212-2 and Delta(9)-THC were equipotent in the wild-type and prodynorphin knock-out mice. Spinal pretreatment with a kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI), did not alter the dose-response curves for either WIN 55,212-2 or Delta(9)-THC in prodynorphin knock-out and wild-type mice. However, the same dose of nor-BNI used blocked U50,488H-induced antinociception in both wild-type and prodynorphin knock-out mice, confirming kappa opioid receptor activity. Pretreatment with SR141716A, a cannabinoid receptor antagonist blocked the antinociceptive actions of both WIN 55,212-2 and Delta(9)-THC. These data support the conclusion that antinociception produced by spinal cannabinoids are likely to be mediated directly through activation of cannabinoid receptors without the requirement for dynorphin release or activation of kappa opioid receptors.

Authors+Show Affiliations

Department of Pharmacology, College of Medicine, University of Arizona Health Sciences Center, 85724 Tucson, AZ, USA Department of Anesthesiology, College of Medicine, University of Arizona Health Sciences Center, Tucson, AZ, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12467995

Citation

Gardell, L R., et al. "Dynorphin-independent Spinal Cannabinoid Antinociception." Pain, vol. 100, no. 3, 2002, pp. 243-248.
Gardell LR, Ossipov MH, Vanderah TW, et al. Dynorphin-independent spinal cannabinoid antinociception. Pain. 2002;100(3):243-248.
Gardell, L. R., Ossipov, M. H., Vanderah, T. W., Lai, J., & Porreca, F. (2002). Dynorphin-independent spinal cannabinoid antinociception. Pain, 100(3), 243-248. https://doi.org/10.1016/S0304-3959(02)00173-2
Gardell LR, et al. Dynorphin-independent Spinal Cannabinoid Antinociception. Pain. 2002;100(3):243-248. PubMed PMID: 12467995.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynorphin-independent spinal cannabinoid antinociception. AU - Gardell,L R, AU - Ossipov,M H, AU - Vanderah,T W, AU - Lai,J, AU - Porreca,F, PY - 2002/12/7/pubmed PY - 2003/3/19/medline PY - 2002/12/7/entrez SP - 243 EP - 248 JF - Pain JO - Pain VL - 100 IS - 3 N2 - Spinal antinociception produced by delta 9-tetrahydro-cannabinol (Delta(9)-THC) and other cannabinoid agonists has been suggested to be mediated by the release of dynorphin acting at the kappa opioid receptor. Alternatively, as cannabinoid receptors are distributed appropriately in the pain transmission pathway, cannabinoid agonists might act directly at the spinal level to inhibit nociception, without requiring dynorphin release. Here, these possibilities were explored using mice with a deletion of the gene encoding prodynorphin. Antinociceptive dose-response curves were constructed for spinal Delta(9)-THC and WIN 55,212-2 in prodynorphin knock-out mice and in wild-type littermates. WIN 55,212-2 and Delta(9)-THC were equipotent in the wild-type and prodynorphin knock-out mice. Spinal pretreatment with a kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI), did not alter the dose-response curves for either WIN 55,212-2 or Delta(9)-THC in prodynorphin knock-out and wild-type mice. However, the same dose of nor-BNI used blocked U50,488H-induced antinociception in both wild-type and prodynorphin knock-out mice, confirming kappa opioid receptor activity. Pretreatment with SR141716A, a cannabinoid receptor antagonist blocked the antinociceptive actions of both WIN 55,212-2 and Delta(9)-THC. These data support the conclusion that antinociception produced by spinal cannabinoids are likely to be mediated directly through activation of cannabinoid receptors without the requirement for dynorphin release or activation of kappa opioid receptors. SN - 0304-3959 UR - https://www.unboundmedicine.com/medline/citation/12467995/Dynorphin_independent_spinal_cannabinoid_antinociception_ L2 - https://linkinghub.elsevier.com/retrieve/pii/00006396-200212000-00005 DB - PRIME DP - Unbound Medicine ER -