P2X receptor-mediated excitation of nociceptive afferents in the normal and arthritic rat knee joint

1 We tested the hypothesis that functional P2X receptors are present on peripheral terminals of primary afferent articular nociceptors in the rat knee joint. Neural activity was recorded extracellularly from the medial articular nerve innervating the knee joint in rats anaesthetized with pentobarbitone. 2 The selective P2X receptor agonist, alpha beta methylene ATP (alpha beta meATP), and the endogenous ligand, ATP, caused a rapid short-lasting excitation of a sub-population of C and A delta nociceptive afferent nerves innervating normal knee joints when injected intra-arterially or intra-articularly, and this effect was antagonized by the non-selective P2 receptor antagonist PPADS. 3 Induction of a chronic (14-21 days) unilateral inflammatory arthritis of the knee joint using locally injected Freund's adjuvant neither increased or decreased responsiveness of joint nociceptors to alpha beta meATP or ATP. 4 Our results support the hypothesis that alpha beta meATP-sensitive P2X receptors are expressed on peripheral nociceptive afferents in the rat knee joint suggesting that they may be involved in the initiation of nociception and pain.