Leukotriene and prostaglandin sensitization of cutaneous high-threshold C- and A-delta mechanonociceptors in the hairy skin of rat hindlimbs.
Single C- and A-delta fibers were isolated from dissected filaments of the saphenous nerve in pentobarbital anesthetized rats and the corresponding cutaneous receptive fields mapped with calibrated von Frey hairs. Nociceptors were characterized by their responses to noxious mechanical, thermal and chemical stimuli, including intradermal injections of leukotriene B4, prostaglandin E2, bradykinin and capsaicin. Leukotriene B4 decreased the mean mechanical threshold by a maximum of 80% within 10 min and for more than 3 h after intradermal injection of 75 ng of leukotriene B4. The degrees of sensitization of a fiber by leukotriene B4 and prostaglandin E2 were highly correlated. A potentiation effect also was observed, in that injection of prostaglandin E2 or leukotriene B4 1 h after the other eicosanoid further lowered the mechanical threshold of a sensitized fiber, whereas fibers that were not sensitized by leukotriene B4 were unaffected by prostaglandin E2. The sensitizing action of leukotriene B4 and prostaglandin E2 was directed to multiple classes of cutaneous nociceptors including 73% of C-polymodal, 60% of C-mechano-heat, 42% of C-mechano-cold nociceptors and 70% of A-delta high-threshold mechanonociceptors. The pain-evoking substances bradykinin and capsaicin activated 81% and 88%, respectively, of the sensitized C-polymodal nociceptors, 17% and 84% of the sensitized-C-mechano-heat nociceptors, 12% and 37% of the sensitized C-mechano-cold nociceptors, and 17% and none of the sensitized A-delta high-threshold mechanociceptors. The responses of C-fibers to bradykinin and capsaicin were highly correlated.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
H A
HA
Department of Anatomy, University of California, San Francisco 94143.
Basbaum
A I
AI
Kwiat
G C
GC
Goetzl
E J
EJ
Levine
J D
JD
D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D004056:Differential Threshold; D015232:Dinoprostone; D006197:Hair; D006614:Hindlimb; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects* / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology; D009619:Nociceptors / Q000187:drug effects* / Q000502:physiology; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D012867:Skin / Q000294:innervation*
D011458:Prostaglandins E; D007975:Leukotriene B4; D015232:Dinoprostone; D002211:Capsaicin; D001920:Bradykinin