The effect of cutaneous mast cell degranulation on sensitivity to heat.
OBJECTIVE
To determine whether depletion of inflammatory mediators from cutaneous mast cells influences cutaneous sensitivity to heat or the thermal hyperalgesia provoked by capsaicin or noradrenaline.


METHODS
Ten healthy men.


RESULTS
Compound 48/80 was introduced by iontophoresis into the forearm. Wheals at the site of compound 48/80 iontophoresis subsided over four pre-treatments, consistent with mast cell degranulation. Flares in the skin surrounding the compound 48/80 sites decreased after the first pre-treatment but persisted to some extent after wheals had disappeared, suggesting that a reagent produced during mast cell activation (e.g., a cytokine or lipoxygenase product released from degranulated mast cells) triggered a residual flare. Sensitivity to heat increased after the second administration of compound 48/80, possibly due to sensitization of thermal nociceptors by inflammatory mediators released from infiltrating leukocytes. However, the compound 48/80 pre-treatment inhibited the hyperalgesic effect of capsaicin. Pre-treatment with compound 48/80 did not prevent axon-reflex vasodilatation to noradrenaline or the hyperalgesic effect of noradrenaline in capsaicin-treated skin.


CONCLUSIONS
Two mechanisms could account for the inhibitory effect of the compound 48/80 pre-treatment on the hyperalgesic effect of capsaicin. First, mast cell products could partly mediate the hyperalgesic effect of capsaicin. Second, partial desensitization of the vanilloid receptor subtype-1 by a reagent produced during mast cell activation (e.g., a lipoxygenase product) could mask the hyperalgesic effect of capsaicin. Mast cells do not appear to mediate the hyperalgesic effect of noradrenaline.
Drummond
P D
PD
School of Psychology, Murdoch University, 6150, Western Australia, Australia, drummond@central.murdoch.edu.au
D000293:Adolescent; D000328:Adult; D001369:Axons / Q000378:metabolism; D002211:Capsaicin / Q000378:metabolism / Q000494:pharmacology*; D006358:Hot Temperature; D006801:Humans; D007249:Inflammation; D007478:Iontophoresis; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology*; D010146:Pain; D012680:Sensitivity and Specificity; D012867:Skin / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D003189:p-Methoxy-N-methylphenethylamine; D002211:Capsaicin; D009638:Norepinephrine