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Spinal anandamide produces analgesia in neuropathic rats: possible CB(1)- and TRPV1-mediated mechanisms.
Neuropharmacology. 2012 Mar; 62(4):1746-55.N

Abstract

The endocannabinoid anandamide (AEA) activates also transient receptor potential vanilloid-1 (TRPV1) channels. However, no data exist on the potential role of spinal TRPV1 activation by AEA in neuropathic pain. We tested the effect of: 1) AEA (5-100 μg), alone or in the presence of an inhibitor of its hydrolysis, and 2) elevated levels of endogenous AEA (following inhibition of AEA hydrolysis), in CCI rats, and the involvement of TRPV1 or cannabinoid CB(1) receptors in the observed effects. Levels of AEA in the spinal cord of CCI rats were measured following all treatments. AEA (50 μg) displayed anti-allodynic and anti-hyperalgesic effects which were abolished by previous antagonism of TRPV1, but not CB(1), receptors. Depending on the administered dose, the selective inhibitor of AEA enzymatic hydrolysis, URB597 (10-100 μg), reduced thermal and tactile nociception via CB(1) or CB(1)/TRPV1 receptors. The anti-nociceptive effects of co-administered per se ineffective doses of AEA (5 μg) and URB597 (5 μg) was abolished by antagonism of CB(1), but not TRPV1, receptors. Spinal AEA levels were increased after CCI, slightly increased further by URB597, 10 μg i.t., and strongly elevated by URB597, 100 μg. Injection of AEA (50 μg) into the lumbar spinal cord led to its dramatic elevation in this tissue, whereas, when a lower dose was used (5 μg) AEA endogenous levels were elevated only in the presence of URB597 (5 μg). We suggest that spinal AEA reduces neuropathic pain via CB(1) or TRPV1, depending on its local concentration.

Authors+Show Affiliations

Dept. of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna str, 31-343 Krakow, Poland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22178705

Citation

Starowicz, K, et al. "Spinal Anandamide Produces Analgesia in Neuropathic Rats: Possible CB(1)- and TRPV1-mediated Mechanisms." Neuropharmacology, vol. 62, no. 4, 2012, pp. 1746-55.
Starowicz K, Makuch W, Osikowicz M, et al. Spinal anandamide produces analgesia in neuropathic rats: possible CB(1)- and TRPV1-mediated mechanisms. Neuropharmacology. 2012;62(4):1746-55.
Starowicz, K., Makuch, W., Osikowicz, M., Piscitelli, F., Petrosino, S., Di Marzo, V., & Przewlocka, B. (2012). Spinal anandamide produces analgesia in neuropathic rats: possible CB(1)- and TRPV1-mediated mechanisms. Neuropharmacology, 62(4), 1746-55. https://doi.org/10.1016/j.neuropharm.2011.11.021
Starowicz K, et al. Spinal Anandamide Produces Analgesia in Neuropathic Rats: Possible CB(1)- and TRPV1-mediated Mechanisms. Neuropharmacology. 2012;62(4):1746-55. PubMed PMID: 22178705.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spinal anandamide produces analgesia in neuropathic rats: possible CB(1)- and TRPV1-mediated mechanisms. AU - Starowicz,K, AU - Makuch,W, AU - Osikowicz,M, AU - Piscitelli,F, AU - Petrosino,S, AU - Di Marzo,V, AU - Przewlocka,B, Y1 - 2011/12/08/ PY - 2011/08/22/received PY - 2011/11/23/revised PY - 2011/11/29/accepted PY - 2011/12/20/entrez PY - 2011/12/20/pubmed PY - 2012/7/28/medline SP - 1746 EP - 55 JF - Neuropharmacology JO - Neuropharmacology VL - 62 IS - 4 N2 - The endocannabinoid anandamide (AEA) activates also transient receptor potential vanilloid-1 (TRPV1) channels. However, no data exist on the potential role of spinal TRPV1 activation by AEA in neuropathic pain. We tested the effect of: 1) AEA (5-100 μg), alone or in the presence of an inhibitor of its hydrolysis, and 2) elevated levels of endogenous AEA (following inhibition of AEA hydrolysis), in CCI rats, and the involvement of TRPV1 or cannabinoid CB(1) receptors in the observed effects. Levels of AEA in the spinal cord of CCI rats were measured following all treatments. AEA (50 μg) displayed anti-allodynic and anti-hyperalgesic effects which were abolished by previous antagonism of TRPV1, but not CB(1), receptors. Depending on the administered dose, the selective inhibitor of AEA enzymatic hydrolysis, URB597 (10-100 μg), reduced thermal and tactile nociception via CB(1) or CB(1)/TRPV1 receptors. The anti-nociceptive effects of co-administered per se ineffective doses of AEA (5 μg) and URB597 (5 μg) was abolished by antagonism of CB(1), but not TRPV1, receptors. Spinal AEA levels were increased after CCI, slightly increased further by URB597, 10 μg i.t., and strongly elevated by URB597, 100 μg. Injection of AEA (50 μg) into the lumbar spinal cord led to its dramatic elevation in this tissue, whereas, when a lower dose was used (5 μg) AEA endogenous levels were elevated only in the presence of URB597 (5 μg). We suggest that spinal AEA reduces neuropathic pain via CB(1) or TRPV1, depending on its local concentration. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/22178705/Spinal_anandamide_produces_analgesia_in_neuropathic_rats:_possible_CB_1___and_TRPV1_mediated_mechanisms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(11)00500-4 DB - PRIME DP - Unbound Medicine ER -