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, alphabeta methylene ATP (alphabetameATP), and the endogenous ligand, ATP, caused a rapid short-lasting excitation of a sub-population of C and Adelta 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 alphabetameATP or ATP. 4. Our results support the hypothesis that alphabetameATP-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.
Dowd
E
E
Department of Pharmacology, University of Edinburgh Medical School.
McQueen
D S
DS
Chessell
I P
IP
Humphrey
P P
PP
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology*; D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000503:physiopathology*; D007719:Knee Joint / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000502:physiology*
D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate