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

1 We have studied the behavioural effects of intraplantar injections of ade nosine 5'-triphosphate (ATP) and related compounds in freely moving rats an d investigated whether these nociceptive effects are augmented in the prese nce of inflammatory mediators. 2 We find that in normal animals ATP and analogues produce dose-dependent n ocifensive behaviour (seen as bursts of elevation of the treated hindpaw), and localized thermal hyperalgesia. The rank order of potency was: alpha,be ta-methyleneadenosine 5'-triphosphate (alpha,beta-methylene ATP) >2-methylt hioadenosine triphosphate (2-methylthio ATP)>ATP. After neonatal treatment with capsaicin, to destroy small calibre primary sensory neurones, nocifens ive behaviour was largely absent. 3 The effects of ATP analogues were assessed in three models of peripheral sensitization: 2 h after dilute intraplantar carrageenan (0.25% w v(-1)); 2 4 h after irradiation of the hindpaw with ultraviolet (U.V.) B; immediately following prostaglandin E-2 (PGE(2)) treatment. In all models the effect o f alpha,beta-methylene ATP was greatly augmented. After carrageenan, signif icant hindpaw-lifting behaviour activity was induced by injection of only 0 .05 nmol of alpha,beta-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 Am will reach levels capable of exciting nociceptors in inflamed versus norma l skin. Our data also suggest the involvement of P2X(3) receptor subunits i n ATP-induced nociception.