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Endocannabinoids decrease neuropathic pain-related behavior in mice through the activation of one or both peripheral CB₁ and CB₂ receptors.
Neuropharmacology. 2014 Feb; 77:441-52.N

Abstract

The two most studied endocannabinoids are anandamide (AEA), principally catalyzed by fatty-acid amide hydrolase (FAAH), and 2-arachidonoyl glycerol (2-AG), mainly hydrolyzed by monoacylglycerol lipase (MGL). Inhibitors targeting these two enzymes have been described, including URB597 and URB602, respectively. Several recent studies examining the contribution of CB₁ and/or CB₂ receptors on the peripheral antinociceptive effects of AEA, 2-AG, URB597 and URB602 in neuropathic pain conditions using either pharmacological tools or transgenic mice separately have been reported, but the exact mechanism is still uncertain. Mechanical allodynia and thermal hyperalgesia were evaluated in 436 male C57BL/6, cnr1KO and cnr2KO mice in the presence or absence of cannabinoid CB₁ (AM251) or CB₂ (AM630) receptor antagonists in a mouse model of neuropathic pain. Peripheral subcutaneous injections of AEA, 2-AG, WIN55,212-2 (WIN; a CB₁/CB₂ synthetic agonist), URB597 and URB602 significantly decreased mechanical allodynia and thermal hyperalgesia. These effects were inhibited by both cannabinoid antagonists AM251 and AM630 for treatments with 2-AG, WIN and URB602 but only by AM251 for treatments with AEA and URB597 in C57BL/6 mice. Furthermore, the antinociceptive effects for AEA and URB597 were observed in cnr2KO mice but absent in cnr1KO mice, whereas the effects of 2-AG, WIN and URB602 were altered in both of these transgenic mice. Complementary genetic and pharmacological approaches revealed that the anti-hyperalgesic effects of 2-AG and URB602 required both CB₁ and CB₂ receptors, but only CB₂ receptors mediated its anti-allodynic actions. The antinociceptive properties of AEA and URB597 were mediated only by CB₁ receptors.

Authors+Show Affiliations

Department of Pharmacology, Université de Montréal, Montréal, Québec, Canada.Faculty of Medicine, School of Optometry, Université de Montréal, Montréal, Québec, Canada.Faculty of Medicine, School of Optometry, Université de Montréal, Montréal, Québec, Canada.Department of Pharmacology, Université de Montréal, Montréal, Québec, Canada; Department of Anesthesiology, Université de Montréal, Montréal, Québec, Canada. Electronic address: pierre.beaulieu@umontreal.ca.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24148808

Citation

Desroches, Julie, et al. "Endocannabinoids Decrease Neuropathic Pain-related Behavior in Mice Through the Activation of One or Both Peripheral CB₁ and CB₂ Receptors." Neuropharmacology, vol. 77, 2014, pp. 441-52.
Desroches J, Charron S, Bouchard JF, et al. Endocannabinoids decrease neuropathic pain-related behavior in mice through the activation of one or both peripheral CB₁ and CB₂ receptors. Neuropharmacology. 2014;77:441-52.
Desroches, J., Charron, S., Bouchard, J. F., & Beaulieu, P. (2014). Endocannabinoids decrease neuropathic pain-related behavior in mice through the activation of one or both peripheral CB₁ and CB₂ receptors. Neuropharmacology, 77, 441-52. https://doi.org/10.1016/j.neuropharm.2013.10.006
Desroches J, et al. Endocannabinoids Decrease Neuropathic Pain-related Behavior in Mice Through the Activation of One or Both Peripheral CB₁ and CB₂ Receptors. Neuropharmacology. 2014;77:441-52. PubMed PMID: 24148808.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endocannabinoids decrease neuropathic pain-related behavior in mice through the activation of one or both peripheral CB₁ and CB₂ receptors. AU - Desroches,Julie, AU - Charron,Sophie, AU - Bouchard,Jean-François, AU - Beaulieu,Pierre, Y1 - 2013/10/19/ PY - 2013/02/15/received PY - 2013/10/05/revised PY - 2013/10/07/accepted PY - 2013/10/24/entrez PY - 2013/10/24/pubmed PY - 2014/8/27/medline KW - 2-AG KW - 2-Arachidonoyl glycerol KW - 2-arachidonoyl glycerol KW - AEA KW - Anandamide KW - CB KW - Cannabinoid receptors KW - DMSO KW - FAAH KW - Fatty-acid amide hydrolase KW - MGL KW - Monoacylglycerol lipase KW - Neuropathic pain KW - anandamide KW - cannabinoid KW - dimethylsulfoxide KW - fatty-acid amide hydrolase KW - monoacylglycerol lipase SP - 441 EP - 52 JF - Neuropharmacology JO - Neuropharmacology VL - 77 N2 - The two most studied endocannabinoids are anandamide (AEA), principally catalyzed by fatty-acid amide hydrolase (FAAH), and 2-arachidonoyl glycerol (2-AG), mainly hydrolyzed by monoacylglycerol lipase (MGL). Inhibitors targeting these two enzymes have been described, including URB597 and URB602, respectively. Several recent studies examining the contribution of CB₁ and/or CB₂ receptors on the peripheral antinociceptive effects of AEA, 2-AG, URB597 and URB602 in neuropathic pain conditions using either pharmacological tools or transgenic mice separately have been reported, but the exact mechanism is still uncertain. Mechanical allodynia and thermal hyperalgesia were evaluated in 436 male C57BL/6, cnr1KO and cnr2KO mice in the presence or absence of cannabinoid CB₁ (AM251) or CB₂ (AM630) receptor antagonists in a mouse model of neuropathic pain. Peripheral subcutaneous injections of AEA, 2-AG, WIN55,212-2 (WIN; a CB₁/CB₂ synthetic agonist), URB597 and URB602 significantly decreased mechanical allodynia and thermal hyperalgesia. These effects were inhibited by both cannabinoid antagonists AM251 and AM630 for treatments with 2-AG, WIN and URB602 but only by AM251 for treatments with AEA and URB597 in C57BL/6 mice. Furthermore, the antinociceptive effects for AEA and URB597 were observed in cnr2KO mice but absent in cnr1KO mice, whereas the effects of 2-AG, WIN and URB602 were altered in both of these transgenic mice. Complementary genetic and pharmacological approaches revealed that the anti-hyperalgesic effects of 2-AG and URB602 required both CB₁ and CB₂ receptors, but only CB₂ receptors mediated its anti-allodynic actions. The antinociceptive properties of AEA and URB597 were mediated only by CB₁ receptors. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/24148808/Endocannabinoids_decrease_neuropathic_pain_related_behavior_in_mice_through_the_activation_of_one_or_both_peripheral_CB₁_and_CB₂_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(13)00480-2 DB - PRIME DP - Unbound Medicine ER -