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The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons.
Neuroscience 2012; 209:32-8N

Abstract

Enhanced nociceptive firing in trigeminal ganglion neurons is a likely reason for migraine pain. In experimental migraine-like conditions induced by the calcitonin gene-related peptide (CGRP), P2X3 receptors abundantly expressed in trigeminal neurons are highly responsive to the excitatory action of extracellular ATP. In this study, we tested whether naproxen, a common antimigraine medicine, could affect the function of P2X3 receptors in the presence or absence of the algogen nerve growth factor (NGF), the level of which is elevated in patients with chronic migraine. We used calcium imaging and patch clamp recordings from rat trigeminal neurons, which were activated by a relative specific P2X3 agonist α,β-meATP or by high potassium-induced depolarization. In the absence of NGF, naproxen dose-dependently (0.1-1 mM) reduced intracellular calcium transients elicited by α,β-meATP. Naproxen also led to a slight, but significant, reduction in calcium transients induced by potassium ions, indicating the involvement of voltage-gated calcium channels. The inhibitory action of 1 mM naproxen was enhanced after NGF pretreatment, suggesting that P2X3 receptors in sensitized neurons are more susceptible to inhibition by high doses of this nonsteroidal anti-inflammatory drug (NSAID). Using patch clamp recordings from HEK293 cells expressing P2X3 receptors, we tested the direct action of naproxen on P2X3 receptor-mediated membrane currents. In clinically relevant concentrations of 0.5 mM, naproxen produced a use-dependent blocking effect on ATP receptors. Kinetic analysis suggests that naproxen inhibited P2X3 receptors via facilitation of fast desensitization, which determines current decay in the continuous presence of the agonist. In summary, we present a novel fast mechanism for the antimigraine action of naproxen, which can act in synergy with the cyclooxygenase inhibition to attenuate headaches.

Authors+Show Affiliations

Department Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern, Finland.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22406417

Citation

Hautaniemi, T, et al. "The Inhibitory Action of the Antimigraine Nonsteroidal Anti-inflammatory Drug Naproxen On P2X3 Receptor-mediated Responses in Rat Trigeminal Neurons." Neuroscience, vol. 209, 2012, pp. 32-8.
Hautaniemi T, Petrenko N, Skorinkin A, et al. The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons. Neuroscience. 2012;209:32-8.
Hautaniemi, T., Petrenko, N., Skorinkin, A., & Giniatullin, R. (2012). The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons. Neuroscience, 209, pp. 32-8. doi:10.1016/j.neuroscience.2012.02.023.
Hautaniemi T, et al. The Inhibitory Action of the Antimigraine Nonsteroidal Anti-inflammatory Drug Naproxen On P2X3 Receptor-mediated Responses in Rat Trigeminal Neurons. Neuroscience. 2012 May 3;209:32-8. PubMed PMID: 22406417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The inhibitory action of the antimigraine nonsteroidal anti-inflammatory drug naproxen on P2X3 receptor-mediated responses in rat trigeminal neurons. AU - Hautaniemi,T, AU - Petrenko,N, AU - Skorinkin,A, AU - Giniatullin,R, Y1 - 2012/02/22/ PY - 2011/12/13/received PY - 2012/01/30/revised PY - 2012/02/10/accepted PY - 2012/3/13/entrez PY - 2012/3/13/pubmed PY - 2012/7/31/medline SP - 32 EP - 8 JF - Neuroscience JO - Neuroscience VL - 209 N2 - Enhanced nociceptive firing in trigeminal ganglion neurons is a likely reason for migraine pain. In experimental migraine-like conditions induced by the calcitonin gene-related peptide (CGRP), P2X3 receptors abundantly expressed in trigeminal neurons are highly responsive to the excitatory action of extracellular ATP. In this study, we tested whether naproxen, a common antimigraine medicine, could affect the function of P2X3 receptors in the presence or absence of the algogen nerve growth factor (NGF), the level of which is elevated in patients with chronic migraine. We used calcium imaging and patch clamp recordings from rat trigeminal neurons, which were activated by a relative specific P2X3 agonist α,β-meATP or by high potassium-induced depolarization. In the absence of NGF, naproxen dose-dependently (0.1-1 mM) reduced intracellular calcium transients elicited by α,β-meATP. Naproxen also led to a slight, but significant, reduction in calcium transients induced by potassium ions, indicating the involvement of voltage-gated calcium channels. The inhibitory action of 1 mM naproxen was enhanced after NGF pretreatment, suggesting that P2X3 receptors in sensitized neurons are more susceptible to inhibition by high doses of this nonsteroidal anti-inflammatory drug (NSAID). Using patch clamp recordings from HEK293 cells expressing P2X3 receptors, we tested the direct action of naproxen on P2X3 receptor-mediated membrane currents. In clinically relevant concentrations of 0.5 mM, naproxen produced a use-dependent blocking effect on ATP receptors. Kinetic analysis suggests that naproxen inhibited P2X3 receptors via facilitation of fast desensitization, which determines current decay in the continuous presence of the agonist. In summary, we present a novel fast mechanism for the antimigraine action of naproxen, which can act in synergy with the cyclooxygenase inhibition to attenuate headaches. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/22406417/The_inhibitory_action_of_the_antimigraine_nonsteroidal_anti_inflammatory_drug_naproxen_on_P2X3_receptor_mediated_responses_in_rat_trigeminal_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(12)00166-2 DB - PRIME DP - Unbound Medicine ER -