Figure 4 | Scientific Reports

Figure 4

From: Systemic desensitization through TRPA1 channels by capsazepine and mustard oil - a novel strategy against inflammation and pain

Figure 4

Capsazepine enemas desensitize local and distant pain responses.

(A) Acute writhing reactions in response to CPZ (531 μM) enemas during the first 5 min after application. Repeated CPZ enemas (twice daily) led to a progressive decrease of writhing responses. A dramatic step reduction was observed after 5 enemas in WT mice. By contrast, TRPA1−/− mice treated with CPZ (531 μM) or WT mice treated with vehicle (PBS) enemas displayed only few writhing that occurred within the first 30 s (each n = 6). (B) Visceromotor responses (VMRs) to CPZ enemas. CPZ enemas twice daily led to a continuous decrease of VMRs in WT mice, similar to the course of writhing reactions. VMRs in response to vehicle were not significantly different from those to CPZ enemas in TRPA1−/− (both n = 6). (A,B) WT CPZ group compared to vehicle group. (C) Repeated CPZ enemas attenuate eye-wipe behavior to AITC (100 μM). Both WT and TRPV1−/− mice treated with CPZ enemas showed a profound reduction of eye-wipe counts compared with vehicle (both n = 6). Controls were WT mice without enemas receiving vehicle (PBS) drops into the eye. (D) CPZ enemas attenuate eye-wipe behavior to CAP (1 mM). WT mice treated with vehicle and TRPA1−/− mice treated with CPZ enemas twice daily for 7 d showed numerous eye-wipe reactions to CAP instillation into the eye, tested 12 h after the last CPZ enema (both n = 6). WT mice treated with CPZ enemas showed profound reduction of eye wipe counts. (E) Thermal and (F) mechanical withdrawal thresholds of both hindpaws during the course of oral CPZ (531 μM) or AITC (500 μM) medication via drinking water. (E) CPZ and AITC over 10 d compared to the vehicle-treated group induced a progressive increase during 3–5 d in withdrawal latencies to radiant heat stimulation, which normalized within 2 weeks of wash-out (each n = 6). (F) Mechanical thresholds to stimulation with an electrodynamic von Frey filament showed no systematic trend under both compounds (each n = 6). All repeated measures ANOVA and Dunnett’s post-test, except in (C,D) Mann Whitney U-test.

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