Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA Department of Pharmacology, University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA Department of Anesthesia, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China Pain Research Program, New Jersey Neuroscience Institute at John F. Kennedy Medical Center, Edison, NJ 08820, USA.
Pain. 2010 Jan;148(1):128-140. doi: 10.1016/j.pain.2009.10.031. Epub 2009 Nov 30.
Dilute capsaicin produces a differential effect on incision-related pain behaviors depending upon the test; it reduces heat hyperalgesia and guarding pain but not mechanical hyperalgesia. This suggests that common mechanisms for heat hyperalgesia and guarding pain occur, and distinct mechanisms exist for mechanical hyperalgesia. The purpose of the present study was to evaluate the effect of capsaicin treatment on the activity of cutaneous nociceptors sensitized by incision to understand the mechanisms for the selective action of dilute capsaicin on incisional pain. We compared the effect of 0.05% capsaicin vs. vehicle treatment on pain behaviors after incision and on the activity of nociceptors from these same rats using the in vitro glabrous skin-nerve preparation. Immunohistochemical expression of protein gene product 9.5 (PGP9.5), neurofilament 200, calcitonin gene related peptide (CGRP) and isolectin B4 (IB4) in skin was also evaluated 1 week after 0.05% capsaicin infiltration. Infiltration of 0.05% capsaicin decreased CGRP and IB4/PGP9.5-immunoreactivity of nociceptors in skin. The same dose of capsaicin that inhibited heat hyperalgesia and guarding behavior interfered with chemo- and heat sensitivity of C-fibers. Neither mechanical hyperalgesia nor mechanosensitivity of nociceptors was affected by capsaicin, suggesting that the concentration of capsaicin used in this study did not cause fiber degeneration. These results demonstrate that nociceptors desensitized by capsaicin contribute to heat hyperalgesia and guarding pain after plantar incision. These putative TRPV1-expressing C-fibers are sensitized to heat and acid after incision, and the transduction of heat and chemical stimuli after plantar incision is impaired by dilute capsaicin.
低浓度辣椒素对切口相关疼痛行为有不同的影响，这取决于测试；它减少了热痛觉过敏和保护疼痛，但不减少机械性痛觉过敏。这表明热痛觉过敏和保护疼痛的共同机制存在，而机械性痛觉过敏存在不同的机制。本研究的目的是评估辣椒素处理对切口致敏的皮肤伤害感受器活性的影响，以了解低浓度辣椒素对切口疼痛选择性作用的机制。我们比较了 0.05%辣椒素与载体处理对切口后疼痛行为的影响，以及对来自这些相同大鼠的伤害感受器活性的影响，使用体外无毛皮肤-神经制备。在 0.05%辣椒素浸润后 1 周，还评估了皮肤中蛋白基因产物 9.5（PGP9.5）、神经丝 200、降钙素基因相关肽（CGRP）和同工凝集素 B4（IB4）的免疫组织化学表达。皮肤中辣椒素浸润降低了伤害感受器中 CGRP 和 IB4/PGP9.5-免疫反应性。同样剂量的辣椒素抑制热痛觉过敏和保护行为，干扰 C 纤维的化学和热敏感性。机械性痛觉过敏和伤害感受器的机械敏感性均不受辣椒素影响，这表明本研究中使用的辣椒素浓度不会引起纤维变性。这些结果表明，辣椒素敏化的伤害感受器有助于足底切口后的热痛觉过敏和保护疼痛。这些假定的 TRPV1 表达 C 纤维在足底切口后对热和酸敏感，并且足底切口后的热和化学刺激的转导被低浓度辣椒素损害。
