Control of P2X3 channel function by metabotropic P2Y2 utp receptors in primary sensory neurons.

Purinergic signaling contributes significantly to pain mechanisms, and the nociceptor-specific P2X3 ATP receptor channel is considered a target in pain therapeutics. Recent findings suggesting the coexpression of metabotropic P2Y receptors with P2X3 implies that ATP release triggers the activation of both ionotropic and metabotropic purinoceptors, with strong potential for functional interaction. Modulation of native P2X3 function by P2Y receptor activation was investigated in rat dorsal root ganglia (DRG) neurons using whole cell patch-clamp recordings.

Neurotrophic factor changes in the rat thick skin following chronic constriction injury of the sciatic nerve.

Background: Cutaneous peripheral neuropathies have been associated with changes of the sensory fiber innervation in the dermis and epidermis. These changes are mediated in part by the increase in local expression of trophic factors. Increase in target tissue nerve growth factor has been implicated in the promotion of peptidergic afferent and sympathetic efferent sprouting following nerve injury.

Delayed reinnervation by nonpeptidergic nociceptive afferents of the glabrous skin of the rat hindpaw in a neuropathic pain model.

Painful peripheral neuropathies have been associated with a reorganization of skin innervation. However, the detailed changes in skin innervation by the different afferent fiber types following a neuropathic nerve injury have never been characterized in an animal model of neuropathic pain. Our objective was to thoroughly characterize such changes in the thick skin of the foot in a well-established rat model of neuropathic pain, namely, the chronic constriction injury (CCI) of the sciatic nerve.

Distribution of P2X(3)-immunoreactive fibers in hairy and glabrous skin of the rat.

The skin is innervated by two populations of unmyelinated sensory fibers, the peptidergic and nonpeptidergic, which transmit nociceptive information to the central nervous system. The peptidergic population expresses neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP) and has both cutaneous and visceral targets. The nonpeptidergic population expresses the purinergic receptor P2X(3), binds the isolectin B4 (IB4), and innervates mainly the epidermis.