The 15-lipoxygenase product, 8R,15S-diHETE, stereospecifically sensitizes C-fiber mechanoheat nociceptors in hairy skin of rat.
1. This study examined the effects of the 15-lipoxygenase product of arachidonic acid metabolism, (8R,15S)-dihydroxyicosa-(5E-9,11,13Z)tetraenoic acid (8R,15S-diHETE), on mechanical thresholds and thermal responses of saphenous nerve cutaneous C-fiber nociceptors that innervate the hairy skin of the rat hindpaw. Single C-fiber mechanoheat nociceptors (C-MH) that had von Frey hair (VFH) thresholds greater than 5 g and were activated by a noxious heat stimulus were chosen for study. We also studied the effects of prostaglandin E2 (PGE2), a cyclooxygenase product of arachidonic acid metabolism, on these nociceptors. 2. The 63 C-MHs studied had a conduction velocity of 0.82 +/- 0.03 m/s (mean +/- SE) and a mechanical threshold of 13.4 +/- 2.4 g. In a subgroup of these (n = 24), the thermal threshold was measured as (44 +/- 1 degree C) (mean +/- SE). 3. 8R,15S-diHETE produced a significant decrease in mechanical threshold of C-MHs (n = 33). The 8R,15S-diHETE-induced sensitization of C-MHs to mechanical stimuli was completely antagonized by coadministration with a stereoisomer, 8S,15S-diHETE (n = 10). 4. The mechanical threshold of C-MHs (n = 10), previously injected with the combination of 8R,15S-diHETE and 8S,15S-diHETE, was significantly reduced by a subsequent injection of PGE2. In a separate group of C-MHs (n = 7), PGE2 was co-injected with 8S,15S-diHETE, which failed to antagonize the sensitizing effect of PGE2 on mechanical threshold. 5. 8R,15S-diHETE also sensitized C-MHs (n = 9) to a thermal stimulus consisting of 37 degrees C for 5 min.(ABSTRACT TRUNCATED AT 250 WORDS)
White
D M
DM
Department of Anatomy, University of California, San Francisco 94143.
Basbaum
A I
AI
Goetzl
E J
EJ
Levine
J D
JD
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D001091:Arachidonate Lipoxygenases / Q000378:metabolism*; D006358:Hot Temperature; D007975:Leukotriene B4 / Q000494:pharmacology* / Q000031:analogs & derivatives; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000294:innervation*; D013237:Stereoisomerism
D007975:Leukotriene B4; C030722:8,15-leukotriene B4; D001091:Arachidonate Lipoxygenases; D001094:Arachidonate 5-Lipoxygenase