ABSTRACT
The cerebrospinal fluid (CSF)-contacting nucleus is implicated in the descending inhibitory pathway in pain processing, whereas the cellular and molecular mechanisms underpinning CSF-contacting nucleus regulating pain signals remains largely elusive. ATP is evidenced to inhibit pain transmission at supraspinal level by the mediation of the receptor P2X, wherein its subtype P2X3 is identified as the most potent. Our present experiment investigated the functionality of P2X3 receptors in CSF-contacting nucleus in the formalin-evoked inflammatory pain. Immunofluorescence and western blot revealed the expression of P2X3 receptors in the CSF-contacting nucleus and their upregulated expression subsequent to administration of formalin in rat model. ATP (a P2X3 receptor agonist, 100nmol/5µl) by intracerebroventricular (i.c.v.) administration ameliorated pain behaviors and enhanced c-Fos immunoreactivity in the neurons of the periaqueductal gray (PAG), both of which were discounted by pre-administration of A-317491 (a selective P2X3 receptor antagonist, 25nmol/5µl). After the CSF-contacting nucleus was ablated by cholera toxin subunit B-saporin, ATP failed to induce analgesia, with the c-Fos immunoreactivity in the PAG neurons remaining intact. Our results validated that P2X3 receptors in the CSF-contacting nucleus are pivotal in inflammatory pain processing via the activation of PAG neurons.
