The effects of inflammation and inflammatory mediators on nociceptive behaviour induced by ATP analogues in the rat

Abstract

1 We have studied the behavioural eects of intraplantar injections of adenosine 5'-triphosphate (ATP) and related compounds in freely moving rats and investigated whether these nociceptive eects are augmented in the presence of in¯ammatory mediators. 2 We ®nd that in normal animals ATP and analogues produce dose-dependent nocifensive behaviour (seen as bursts of elevation of the treated hindpaw), and localized thermal hyperalgesia. The rank order of potency was: a,b-methyleneadenosine 5'-triphosphate (a,b-methylene ATP) 42-methylthioadenosine triphosphate (2-methylthio ATP)4ATP. After neonatal treatment with capsaicin, to destroy small calibre primary sensory neurones, nocifensive behaviour was largely absent. 3 The eects of ATP analogues were assessed in three models of peripheral sensitization: 2 h after dilute intraplantar carrageenan (0.25% w v 71 ); 24 h after irradiation of the hindpaw with ultraviolet (U.V.) B; immediately following prostaglandin E 2 (PGE 2 ) treatment. In all models the eect of a,bmethylene ATP was greatly augmented. After carrageenan, signi®cant hindpaw-lifting behaviour activity was induced by injection of only 0.05 nmol of a,b-methylene ATP, some 100 times less than necessary in normal skin. 4 Our data suggest that it is much more likely that endogenous levels of ATP will reach levels capable of exciting nociceptors in in¯amed versus normal skin. Our data also suggest the involvement of P2X 3 receptor subunits in ATP-induced nociception.

Sensory and Signaling Mechanisms of Bradykinin, Eicosanoids, Platelet-Activating Factor, and Nitric Oxide in Peripheral Nociceptors

“…PGE 2 enhanced the nocifensive reaction as well as the thermal and mechanical hyperalgesia in rats induced by ␣,␤-methylene-ATP, an activator of fast inactivating P2X receptor channels for extracellular ATP (262,759). However, ATP-(or UTP-) induced thermal hyperalgesia also depends essentially on metabotropic P2Y receptors that stimulate secondary PGE 2 formation which finally is responsible for the nociceptor sensitization, most likely achieved through sensitizing TRPV1 (462).…”

Emerging Peripheral Receptor Targets for Deep-tissue Craniofacial Pain Therapies

“…The injection of ATP analogues into the hindpaw of rats has also been reported to elicit nociceptive paw-lifting behavior (Hamilton et al, 1999), while intrathecal administration of ATP analogues produces thermal hyperalgesia (Tsuda et al, 1999). These responses indicate that ATP can evoke pain which is now known to be mediated via ATP purinoceptors (for review, see Hwang and Oh, 2007;Wirkner et al, 2007).…”

Expression of P2X3and its colocalization with trpv1 in the human dental pulp

“…Paukert et al 32) showed that inflammatory mediator such as substance P and bradykinin potentiate the ATP-evoked currents in oocytes expressing P2X3 by lowering the desensitization rate through phosphorylation of P2X3. Hamilton et al 7) also reported that nociceptive action of ATP are markedly augmented in the presence of inflammation or inflammatory mediators and it was attributed that extracellular levels of ATP will reach levels capable of activating nociceptors in inflamed tissue. There are several ways in which the enhanced responses might arise.…”

“…ATP can be released actively or passively by cell lysis during tissue damage, which in turn may activate P2X3 receptors to initiate nociceptive signals. This effect may be exaggerated under conditions of inflammation 6,7) . Many previous studies showed the expression of P2X3 in the central and peripheral neurons 1,4,[8][9][10] .…”