Stimulation of PAR-2 excites and sensitizes rat cutaneous C-nociceptors to heat.
Proteinase-activated receptor 2 (PAR-2) is expressed on many nociceptive neurons. Application of PAR-2 agonists has been shown to induce behavioral signs of hyperalgesia. We investigated effects of the rat PAR-2 agonist SLIGRL-NH2 in the isolated rat skin-saphenous nerve preparation. SLIGRL-NH2 (100 microM) excited 20% of all C-fiber nociceptors tested. In addition, C-fiber nociceptors were sensitized to heat after SLIGRL-NH2 application resulting in an increase in response magnitude and a decrease of heat threshold. The PAR-2-inactive control peptide LRGILS-NH2 had no effect. The mechanical sensitivity of C-fibers was not affected by SLIGRL-NH2. PAR-2-mediated excitation and sensitization of primary nociceptors may contribute to PAR-2-mediated hyperalgesia.
Aventis Pharma Deutschland GmbH, DG Thrombosis and Degenerative Joint Diseases, Industriepark Hoechst, D-65929 Frankfurt, Germany.
Danping
D
Ding-Pfennigdorff
Beate
B
Averbeck
Martin
M
Michaelis
D000200:Action Potentials / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006358:Hot Temperature; D066298:In Vitro Techniques; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009842:Oligopeptides / Q000494:pharmacology; D010146:Pain / Q000378:metabolism; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D044464:Receptor, PAR-2 / Q000819:agonists / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D012867:Skin / Q000187:drug effects / Q000294:innervation / Q000528:radiation effects; D018709:Statistics, Nonparametric
D009842:Oligopeptides; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide