Figure 5

Local and systemic desensitization of peptidergic sensory nerves by capsazepine (CPZ) indicated by altered release of calcitonin gene-related peptide (CGRP).

(A) Acute CGRP release from isolated colon preparations of WT mice induced by CPZ (100 μM); subsequent mustard oil (AITC, 100 μM) exposures fail to induce CGRP release, while unspecific depolarization by KCl (60 mM) is effective as normal. Data are means + SEMs (n = 8). (B–D) CPZ (100 μM)- and AITC (100 μM)-induced colonic CGRP release was abolished in mice pretreated with twice daily CPZ enemas for 7 d until the day before the release experiment, whereas CAP (1 μM)-induced colonic CGRP-release was strongly reduced but not abolished in these mice compared with controls. (**P < 0.01, ***P < 0.001, Mann Whitney U-test, each n = 6). (E) Similarly, AITC (100 μM)-induced CGRP release was abolished in isolated skin preparations from the hindpaws of mice pretreated with CPZ enemas. (F) In contrast, CAP (1 μM)-induced CGRP release was strongly reduced from the skin of these mice compared with controls. (**P < 0.01, ***P < 0.001, Mann Whitney U-test, each n = 6). Note that all KCl (60 mM) responses following desensitized CPZ and AITC responses were normal (B,C,E), whereas the KCl responses of the incompletely desensitized CAP-stimulated, neuron population (D,F) were as much reduced as in all control experiments, suggesting CGRP store depletion which is prevented by effective desensitization of the CPZ/AITC sensitive neuron subpopulation.