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

• Main Authors: Marina Arribas-Blázquez, Luis Alcides Olivos-Oré, María Victoria Barahona, Mercedes Sánchez de la Muela, Virginia Solar, Esperanza Jiménez, Javier Gualix, J. Michael McIntosh, Antonio Ferrer-Montiel, María Teresa Miras-Portugal, Antonio R. Artalejo
• Format: Article
• Language: English
• Published: MDPI AG 2019-01-01
• Series: International Journal of Molecular Sciences
• Subjects: P2X3 receptors; P2X7 receptors; TRPV1 channels; α9 nicotinic acetylcholine receptors; neuropathic pain; chromaffin cells; adrenal medulla; stress
• Online Access: http://www.mdpi.com/1422-0067/20/1/155

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.