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Modulation of trigeminal sensory neuron activity by the dual cannabinoid-vanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2-chloroethylamide.
Br J Pharmacol 2004; 141(7):1118-30BJ

Abstract

1. Peripheral cannabinoids have been shown to suppress nociceptive neurotransmission in a number of behavioral and neurophysiological studies. It is not known, however, whether cannabinoids exert this action through direct interactions with nociceptors in the periphery and/or if other processes are involved. To gain a better understanding of the direct actions of cannabinoid-vanilloid agonists on sensory neurons, we examined the effects of these compounds on trigeminal ganglion (TG) neurons in vitro. 2. AEA (EC(50)=11.0 microM), NADA (EC(50)=857 nM) and arachidonyl-2-chloroethylamide ACEA (EC(50)=14.0 microM) each evoked calcitonin gene-related peptide (CGRP) release from TG neurons. The TRPV1 antagonists iodo-resiniferatoxin (I-RTX) and capsazepine (CPZ) each obtunded AEA-, NADA-, ACEA- and capsaicin (CAP)-evoked CGRP release with individually equivalent IC(50)'s for each of the compounds (I-RTX IC(50) range=2.6-4.0 nM; CPZ IC(50) range=523-1140 microM). 3. The pro-inflammatory mediator prostaglandin E(2) significantly increased the maximal effect of AEA-evoked CGRP release without altering the EC(50). AEA, ACEA and CAP stimulated cAMP accumulation in TG neurons in a calcium- and TRPV1-dependent fashion. Moreover, the protein kinase inhibitor staurosporine significantly inhibited AEA- and CAP-evoked CGRP release. 4. The pungency of AEA, NADA, ACEA and CAP in the rat eye-wipe assay was also assessed. Interestingly, when applied intraocularly, NADA or CAP each produced nocifensive responses, while AEA or ACEA did not. 5. Finally, the potential inhibitory effects of these cannabinoids on TG nociceptors were evaluated. Neither AEA nor ACEA decreased CAP-evoked CGRP release. Furthermore, neither of the cannabinoid receptor type 1 antagonists SR141716A nor AM251 had any impact on either basal or CAP-evoked CGRP release. AEA also did not inhibit 50 mM K(+)-evoked CGRP release and did not influence bradykinin-stimulated inositol phosphate accumulation. 6. We conclude that the major action of AEA, NADA and ACEA on TG neurons is excitatory, while, of these, only NADA is pungent. These findings are discussed in relation to our current understanding of interactions between the cannabinoid and vanilloid systems and nociceptive processing in the periphery.

Authors+Show Affiliations

Department of Pharmacology, The University of Texas Health Science Center at San Antonio, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15006899

Citation

Price, Theodore J., et al. "Modulation of Trigeminal Sensory Neuron Activity By the Dual Cannabinoid-vanilloid Agonists Anandamide, N-arachidonoyl-dopamine and Arachidonyl-2-chloroethylamide." British Journal of Pharmacology, vol. 141, no. 7, 2004, pp. 1118-30.
Price TJ, Patwardhan A, Akopian AN, et al. Modulation of trigeminal sensory neuron activity by the dual cannabinoid-vanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2-chloroethylamide. Br J Pharmacol. 2004;141(7):1118-30.
Price, T. J., Patwardhan, A., Akopian, A. N., Hargreaves, K. M., & Flores, C. M. (2004). Modulation of trigeminal sensory neuron activity by the dual cannabinoid-vanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2-chloroethylamide. British Journal of Pharmacology, 141(7), pp. 1118-30.
Price TJ, et al. Modulation of Trigeminal Sensory Neuron Activity By the Dual Cannabinoid-vanilloid Agonists Anandamide, N-arachidonoyl-dopamine and Arachidonyl-2-chloroethylamide. Br J Pharmacol. 2004;141(7):1118-30. PubMed PMID: 15006899.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modulation of trigeminal sensory neuron activity by the dual cannabinoid-vanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2-chloroethylamide. AU - Price,Theodore J, AU - Patwardhan,Amol, AU - Akopian,Armen N, AU - Hargreaves,Kenneth M, AU - Flores,Christopher M, Y1 - 2004/03/08/ PY - 2004/3/10/pubmed PY - 2005/4/15/medline PY - 2004/3/10/entrez SP - 1118 EP - 30 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 141 IS - 7 N2 - 1. Peripheral cannabinoids have been shown to suppress nociceptive neurotransmission in a number of behavioral and neurophysiological studies. It is not known, however, whether cannabinoids exert this action through direct interactions with nociceptors in the periphery and/or if other processes are involved. To gain a better understanding of the direct actions of cannabinoid-vanilloid agonists on sensory neurons, we examined the effects of these compounds on trigeminal ganglion (TG) neurons in vitro. 2. AEA (EC(50)=11.0 microM), NADA (EC(50)=857 nM) and arachidonyl-2-chloroethylamide ACEA (EC(50)=14.0 microM) each evoked calcitonin gene-related peptide (CGRP) release from TG neurons. The TRPV1 antagonists iodo-resiniferatoxin (I-RTX) and capsazepine (CPZ) each obtunded AEA-, NADA-, ACEA- and capsaicin (CAP)-evoked CGRP release with individually equivalent IC(50)'s for each of the compounds (I-RTX IC(50) range=2.6-4.0 nM; CPZ IC(50) range=523-1140 microM). 3. The pro-inflammatory mediator prostaglandin E(2) significantly increased the maximal effect of AEA-evoked CGRP release without altering the EC(50). AEA, ACEA and CAP stimulated cAMP accumulation in TG neurons in a calcium- and TRPV1-dependent fashion. Moreover, the protein kinase inhibitor staurosporine significantly inhibited AEA- and CAP-evoked CGRP release. 4. The pungency of AEA, NADA, ACEA and CAP in the rat eye-wipe assay was also assessed. Interestingly, when applied intraocularly, NADA or CAP each produced nocifensive responses, while AEA or ACEA did not. 5. Finally, the potential inhibitory effects of these cannabinoids on TG nociceptors were evaluated. Neither AEA nor ACEA decreased CAP-evoked CGRP release. Furthermore, neither of the cannabinoid receptor type 1 antagonists SR141716A nor AM251 had any impact on either basal or CAP-evoked CGRP release. AEA also did not inhibit 50 mM K(+)-evoked CGRP release and did not influence bradykinin-stimulated inositol phosphate accumulation. 6. We conclude that the major action of AEA, NADA and ACEA on TG neurons is excitatory, while, of these, only NADA is pungent. These findings are discussed in relation to our current understanding of interactions between the cannabinoid and vanilloid systems and nociceptive processing in the periphery. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/15006899/Modulation_of_trigeminal_sensory_neuron_activity_by_the_dual_cannabinoid_vanilloid_agonists_anandamide_N_arachidonoyl_dopamine_and_arachidonyl_2_chloroethylamide_ L2 - https://doi.org/10.1038/sj.bjp.0705711 DB - PRIME DP - Unbound Medicine ER -