Leukotriene B4 decreases the mechanical and thermal thresholds of C-fiber nociceptors in the hairy skin of the rat.
1. We have recently shown that leukotriene B4 (LTB4), a product of the 5-lipoxygenase pathway of arachidonic acid metabolism, sensitizes nociceptors to mechanical stimuli. The present study examined whether LTB4 also induces a heat sensitization of cutaneous C-fiber nociceptors. The C-fiber nociceptors studied had von Frey hair thresholds greater than 5 g and were characterized according to their responses to noxious heat and chemical stimuli, including glacial acetic acid, bradykinin, and capsaicin. Thirty-four of the C-fibers that were activated by intense thermal stimulation were also activated by topical application of glacial acetic acid. They were classified as C-polymodal nociceptors (2, 28). Those that were activated by intense mechanical and thermal stimulation, but were unresponsive to acid, were classified as C-mechanoheat nociceptors (27). 2. Ninety-four percent of C-polymodal nociceptors and 60% of C-mechanoheat nociceptors were sensitized by LTB4. All C-fiber nociceptors that showed a decrease of their heat threshold also had a decrease of their mechanical threshold. LTB4 (75 ng) lowered the average heat threshold from 45 degrees C to 35 degrees C and produced an average decrease in the mechanical threshold of 86%. 3. The magnitude of the LTB4-evoked decrease in thermal threshold was similar to that produced by 75 ng of prostaglandin E2 (PGE2). These data demonstrate that LTB4 sensitizes C-mechanoheat nociceptors to both mechanical and thermal stimuli. 4. We conclude that LTB4 may contribute to the component of hyperalgesia that is resistant to nonsteroidal anti-inflammatory agents.
Martin
H A
HA
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; D004558:Electric Stimulation; D006358:Hot Temperature; D007975:Leukotriene B4 / Q000494:pharmacology*; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D011919:Rats, Inbred Strains; D012684:Sensory Thresholds / Q000187:drug effects*; D012867:Skin / Q000294:innervation*; D012879:Skin Physiological Phenomena
D007975:Leukotriene B4