P2X3 receptors contribute to transition from acute to chronic muscle pain

Abstract

This study aimed to evaluate whether the development and/or maintenance of chronic-latent muscle hyperalgesia is modulated by P2X3 receptors. We also evaluate the expression of P2X3 receptors and PKCε of dorsal root ganglions during these processes. A mouse model of chronic-latent muscle hyperalgesia, induced by carrageenan and evidenced by PGE 2 , was used. Mechanical muscle hyperalgesia was measured by Randall-Selitto analgesimeter. The involvement of P2X3 receptors was analyzed by using the selective P2X3 receptors antagonist A-317491 by intramuscular or intrathecal injections. Expression of P2X3 and PKCε in dorsal root ganglion (L4-S1) were evaluated by Western blotting. Intrathecal blockade of P2X3 receptors previously to carrageenan prevented the development and maintenance of acute and chronic-latent muscle hyperalgesia, while intramuscular blockade of P2X3 receptors previously to carrageenan only reduced the acute muscle hyperalgesia and had no effect on chronic-latent muscle hyperalgesia. Intrathecal, but not intramuscular, blockade of P2X3 receptors immediately before PGE 2 , in animals previously sensitized by carrageenan, reversed the chronic-latent muscle hyperalgesia. There was an increase in total and phosphorylated PKCε 48 h after the beginning of acute muscle hyperalgesia, and in P2X3 receptors at the period of chronic muscle hyperalgesia. P2X3 receptors expressed on spinal cord dorsal horn contribute to transition from acute to chronic muscle pain. We also suggest an interaction of PKCε and P2X3 receptors in this process. Therefore, we point out P2X3 receptors of the spinal cord dorsal horn as a pharmacological target to prevent the development or reverse the chronic muscle pain conditions.

Polyphyllin VI screened from Chonglou by cell membrane immobilized chromatography relieves inflammatory pain by inhibiting inflammation and normalizing the expression of P2X3 purinoceptor

“…Specific targeting of the P2X 3 receptor by genetic deletion and knockdown results in a hypoalgesic phenotype ( Butler and Meegan, 2008 ). Studies have shown that the pharmacological blockade of P2X 3 receptors completely blocked specific types of chronic inflammatory and neuropathic pain ( Kaan et al, 2010 ; Xu et al, 2012 ; Jorge et al, 2020 ). Peripheral nerve injury differentially alters the functional expression of P2X 3 receptors in small- and large-diameter primary afferent neurons ( Inoue, 2021 ).…”

Mechanisms of ATP release in pain: role of pannexin and connexin channels

“…In particular, activation of the homomeric P2X3 and P2X2/3 receptors in sensory neurons have been associated with acute pain behaviors [ 17 – 19 ]. For example, blocking P2X3 receptors with the selective P2X3 receptor antagonist A-317491 prevented acute muscle hyperalgesia, but had no effect on chronic-muscle pain [ 18 ]. Conversely, the activation and upregulation of P2X4 receptors on glial cells (i.e., microglia) are linked to the pathogenesis and development of neuropathic pain and mechanical allodynia, thus representing a pathway promoting the development of chronic pain [ 20 – 22 ].…”

TRPM3-mediated dynamic mitochondrial activity in nerve growth factor–induced latent sensitization of chronic low back pain

“…21 PKC Ɛ mediates latent sensitization of inflammatory pain and contributes to chronification of muscle pain. 1,23 TRPM3 acts upstream of TRPV1 to drive DRG neuronal hyperexcitability. 38 Therefore, mitoflash outbreak may promote TRPV1 sensitivity via PKC Ɛ pathway, thereby contributing to TRPM3-mediated latent sensitization (Fig.…”