This study addresses the hypothesis that the early symptoms of chemica
lly induced skin irritation are neurally mediated. Several approaches
were used to affect nerve transmission in adult Balb/c female mice. Th
ese included general anesthesia (i.e., sodium pentobarbital), systemic
capsaicin treatment, and pretreatment with specific pharmacological a
ntagonists of the neuropeptides substance P (SP) and neurokinin A (NKA
). After these treatments, a strongly irritating dose of dinitrofluoro
benzene (DNFB) was applied to the ear and its swelling was measured ov
er several postexposure times as an index of tissue irritation. Ear sw
elling in Nembutal (30 mg/kg)-anesthetized mice was depressed 62 and 7
6% at 4 and 24 hr postexposure compared to DNFB-treated unanesthetized
animals measured at the same time points. Multiple injections of caps
aicin (cumulative dose 30 mg/kg) depressed DNFB-ear swelling relative
to non-capsaicin, DNFB-treated controls by 15, 40 (ip), and 44 and 43%
(sc) at 4 and 24 hr postexposure, respectively. In mice exposed to ac
ute or multiple injections of the SP antagonist CP-96,345 before DNFB
application, ear swelling was depressed (relative to DNFB-treated anim
als) by 64 and 36% (acute, sc, 10 mg/kg) and 91 and 88% (multiple, ip,
cumulative 35 mg/kg) at 0.5 and 1 hr postexposure, respectively. Mice
exposed to the NKA antagonist, SR 48958, alone and in combination wit
h the SP antagonist CP-96,345 were also examined after DNFB applicatio
n. Ear swelling was diminished in mice pretreated with the NKA antagon
ist (1.0 mg/kg) by 17, 24, 34, and 40% at 0.5, 1, 4, and 24 hr postexp
osure. When used in combination with the SP antagonist, DNFB-induced e
ar swelling was reduced by 95% compared to unantagonized, DNFB-exposed
mice at the 0.5- and 1-hr time points and remained significantly depr
essed by 33 and 468 at 4 and 24 hr postexposure. Taken in concert, the
se data suggest that neuropeptides, especially the tachykinins SP and
NKA, modulate the early stages of chemically induced skin irritation.
(C) 1995 Academic Press, Inc.