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The antinociceptive effects of local injections of propofol in rats are mediated in part by cannabinoid CB1 and CB2 receptors.
Anesth Analg. 2007 Jun; 104(6):1563-9, table of contents.A&A

Abstract

BACKGROUND

Propofol can inhibit fatty acid amidohydrolase, the enzyme responsible for the metabolism of anandamide (an endocannabinoid). To study the potential antinociceptive effect of propofol, we administered different doses (0.005, 0.05, 0.5, 5, and 500 microg) of the anesthetic in the hind paw of animals to determine an ED50. To further investigate the mechanisms by which propofol produced its antinociceptive effect, we used specific antagonists for the cannabinoid CB1 (AM251) and CB2 (AM630) receptors and measured fatty-acid amide/endocannabinoid (anandamide, 2-arachidonylglycerol, and palmitoylethanolamide) concentrations in skin paw tissues.

METHODS

Formalin tests were performed on 65 Wistar rats allocated to six different groups: 1) control (Intralipidtrade mark 10%); 2) propofol (ED50 dose); 3) AM251; 4) AM251 + propofol; 5) AM630; 6) AM630 + propofol. Drugs were injected subcutaneously in the dorsal surface of the hind paw (50 microL) 15 min before 2.5% formalin injection into the same paw. Fatty-acid amide/endocannabinoid levels were measured by high performance liquid chromatography/mass spectrometry analysis.

RESULTS

Propofol produced a dose-dependent antinociceptive effect for the early and late phases of the formalin test with an ED50 of 0.08 +/- 0.061 microg for the latter phase. This effect was antagonized by AM251 and AM630. It was locally mediated, since a higher dose of propofol given in the contralateral paw was not antinociceptive. Finally, only paw concentrations of palmitoylethanolamide were significantly increased.

CONCLUSION

In a test of inflammatory pain, locally injected propofol decreased pain behavior in a dose-dependent manner. This antinociceptive effect was mediated, in part, by CB1 and CB2 receptors.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Medicine, Université de Montréal-CHUM, Montréal, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17513659

Citation

Guindon, Josée, et al. "The Antinociceptive Effects of Local Injections of Propofol in Rats Are Mediated in Part By Cannabinoid CB1 and CB2 Receptors." Anesthesia and Analgesia, vol. 104, no. 6, 2007, 1563-9, table of contents.
Guindon J, LoVerme J, Piomelli D, et al. The antinociceptive effects of local injections of propofol in rats are mediated in part by cannabinoid CB1 and CB2 receptors. Anesth Analg. 2007;104(6):1563-9, table of contents.
Guindon, J., LoVerme, J., Piomelli, D., & Beaulieu, P. (2007). The antinociceptive effects of local injections of propofol in rats are mediated in part by cannabinoid CB1 and CB2 receptors. Anesthesia and Analgesia, 104(6), 1563-9, table of contents.
Guindon J, et al. The Antinociceptive Effects of Local Injections of Propofol in Rats Are Mediated in Part By Cannabinoid CB1 and CB2 Receptors. Anesth Analg. 2007;104(6):1563-9, table of contents. PubMed PMID: 17513659.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The antinociceptive effects of local injections of propofol in rats are mediated in part by cannabinoid CB1 and CB2 receptors. AU - Guindon,Josée, AU - LoVerme,Jesse, AU - Piomelli,Daniele, AU - Beaulieu,Pierre, PY - 2007/5/22/pubmed PY - 2007/6/15/medline PY - 2007/5/22/entrez SP - 1563-9, table of contents JF - Anesthesia and analgesia JO - Anesth Analg VL - 104 IS - 6 N2 - BACKGROUND: Propofol can inhibit fatty acid amidohydrolase, the enzyme responsible for the metabolism of anandamide (an endocannabinoid). To study the potential antinociceptive effect of propofol, we administered different doses (0.005, 0.05, 0.5, 5, and 500 microg) of the anesthetic in the hind paw of animals to determine an ED50. To further investigate the mechanisms by which propofol produced its antinociceptive effect, we used specific antagonists for the cannabinoid CB1 (AM251) and CB2 (AM630) receptors and measured fatty-acid amide/endocannabinoid (anandamide, 2-arachidonylglycerol, and palmitoylethanolamide) concentrations in skin paw tissues. METHODS: Formalin tests were performed on 65 Wistar rats allocated to six different groups: 1) control (Intralipidtrade mark 10%); 2) propofol (ED50 dose); 3) AM251; 4) AM251 + propofol; 5) AM630; 6) AM630 + propofol. Drugs were injected subcutaneously in the dorsal surface of the hind paw (50 microL) 15 min before 2.5% formalin injection into the same paw. Fatty-acid amide/endocannabinoid levels were measured by high performance liquid chromatography/mass spectrometry analysis. RESULTS: Propofol produced a dose-dependent antinociceptive effect for the early and late phases of the formalin test with an ED50 of 0.08 +/- 0.061 microg for the latter phase. This effect was antagonized by AM251 and AM630. It was locally mediated, since a higher dose of propofol given in the contralateral paw was not antinociceptive. Finally, only paw concentrations of palmitoylethanolamide were significantly increased. CONCLUSION: In a test of inflammatory pain, locally injected propofol decreased pain behavior in a dose-dependent manner. This antinociceptive effect was mediated, in part, by CB1 and CB2 receptors. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/17513659/The_antinociceptive_effects_of_local_injections_of_propofol_in_rats_are_mediated_in_part_by_cannabinoid_CB1_and_CB2_receptors_ L2 - https://doi.org/10.1213/01.ane.0000263278.05423.a3 DB - PRIME DP - Unbound Medicine ER -