2. Academic Validation
  3. Overexpression of P2X3 and P2X7 Receptors and TRPV1 Channels in Adrenomedullary Chromaffin Cells in a Rat Model of Neuropathic Pain

Overexpression of P2X3 and P2X7 Receptors and TRPV1 Channels in Adrenomedullary Chromaffin Cells in a Rat Model of Neuropathic Pain

  • Int J Mol Sci. 2019 Jan 3;20(1):155. doi: 10.3390/ijms20010155.
Marina Arribas-Blázquez 1 2,  Luis Alcides Olivos-Oré 3 4,  María Victoria Barahona 5 6,  Mercedes Sánchez de la Muela 7,  Virginia Solar 8,  Esperanza Jiménez 9,  Javier Gualix 10 11,  J Michael McIntosh 12 13,  Antonio Ferrer-Montiel 14,  María Teresa Miras-Portugal 15 16,  Antonio R Artalejo 17 18
Affiliations

Affiliations

  • 1 Department of Pharmacology and Toxicology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. marina.arribas@vet.ucm.es.
  • 2 Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense de Madrid, 28040 Madrid, Spain. marina.arribas@vet.ucm.es.
  • 3 Department of Pharmacology and Toxicology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. olivos@ucm.es.
  • 4 Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense de Madrid, 28040 Madrid, Spain. olivos@ucm.es.
  • 5 Department of Pharmacology and Toxicology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. vbg@ucm.es.
  • 6 Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense de Madrid, 28040 Madrid, Spain. vbg@ucm.es.
  • 7 Department of Animal Medicine and Surgery, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. sdlmuela@vet.ucm.es.
  • 8 Department of Pharmacology and Toxicology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. virvir93@gmail.com.
  • 9 Department of Pharmacology and Toxicology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. esperanzajim@gmail.com.
  • 10 Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense de Madrid, 28040 Madrid, Spain. jgualix@ucm.es.
  • 11 Department of Biochemistry and Molecular Biology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. jgualix@ucm.es.
  • 12 George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA. mcintosh.mike@gmail.com.
  • 13 Departments of Biology and Psychiatry, University of Utah, Salt Lake City, UT 84112, USA. mcintosh.mike@gmail.com.
  • 14 Instituto de Biología Molecular y Celular (IBMC), Universitas Miguel Hernández, 03202 Elche, Spain. aferrer@umh.es.
  • 15 Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense de Madrid, 28040 Madrid, Spain. mtmiras@vet.ucm.es.
  • 16 Department of Biochemistry and Molecular Biology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. mtmiras@vet.ucm.es.
  • 17 Department of Pharmacology and Toxicology, Veterinary Faculty, Universidad Complutense de Madrid, 28040 Madrid, Spain. antonio.artalejo@vet.ucm.es.
  • 18 Instituto Universitario de Investigación en Neuroquímica, Universidad Complutense de Madrid, 28040 Madrid, Spain. antonio.artalejo@vet.ucm.es.
PMID: 30609840 DOI: 10.3390/ijms20010155
Abstract

We have tested the hypothesis that neuropathic pain acting as a stressor drives functional plasticity in the sympathoadrenal system. The relation between neuropathic pain and adrenal medulla function was studied with behavioral, immunohistochemical and electrophysiological techniques in rats subjected to chronic constriction injury of the sciatic nerve. In slices of the adrenal gland from neuropathic Animals, we have evidenced increased cholinergic innervation and spontaneous synaptic activity at the splanchnic nerve⁻chromaffin cell junction. Likewise, adrenomedullary chromaffin cells displayed enlarged acetylcholine-evoked currents with greater sensitivity to α-conotoxin RgIA, a selective blocker of α9 subunit-containing nicotinic acetylcholine receptors, as well as increased exocytosis triggered by voltage-activated CA2+ entry. Altogether, these adaptations are expected to facilitate Catecholamine output into the bloodstream. Last, but most intriguing, functional and immunohistochemical data indicate that P2X3 and P2X7 purinergic receptors and transient receptor potential vanilloid-1 (TRPV1) channels are overexpressed in chromaffin cells from neuropathic Animals. These latter observations are reminiscent of molecular changes characteristic of peripheral sensitization of nociceptors following the lesion of a peripheral nerve, and suggest that similar phenomena can occur in other tissues, potentially contributing to behavioral manifestations of neuropathic pain.

Keywords

P2X3 receptors; P2X7 receptors; TRPV1 channels; adrenal medulla; chromaffin cells; neuropathic pain; stress; α9 nicotinic acetylcholine receptors.

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