Peripheral PAR-2 triggers thermal hyperalgesia and nociceptive responses in rats.
Protease-activated receptor-2 (PAR-2), a member of the G protein-coupled, seven trans-membrane domain receptor family, is activated by trypsin/tryptase and present in various tissues including the primary sensory neurons, playing a role in development of neurogenic inflammation. The present study examined if activation of peripheral PAR-2 could modulate nociception in the rat. Expression of mRNA for PAR-2 was confirmed in the L4-6 dorsal root ganglia, but not spinal cord. The PAR-2-activating peptide SLIGRL-NH2 administered by the intraplantar (i.pl.) route, produced thermal, but not mechanical, hyperalgesia in the rat, although the PAR-2-inactive control peptide LSIGRL-NH2 had no effect. Not only the PAR-2-activating but also inactive peptides elicited nociceptive behavior (licking/biting) in the intact rats, whereas only the former peptide produced such behavior in the rats that had received repeated administration of compound 48/80 for mast cell depletion. These data provide novel evidence that activation of peripheral PAR-2 is pro-nociceptive, producing thermal hyperalgesia and also triggering pain sensation, by itself, independently of mast cell degranulation.
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Kinki University, Higashi-Osaka, Osaka, Japan.
A
A
Kawabata
N
N
Kawao
R
R
Kuroda
A
A
Tanaka
H
H
Itoh
H
H
Nishikawa
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D006930:Hyperalgesia / Q000378:metabolism*; D008297:Male; D009475:Neurons, Afferent / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000378:metabolism; D010812:Physical Stimulation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology
D009842:Oligopeptides; D012333:RNA, Messenger; D044463:Receptor, PAR-1; D044464:Receptor, PAR-2; D018179:Receptors, Thrombin; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide