Ishikura Toru, Suzuki Hitoshi, Shoguchi Kanako, Koreeda Yuki, Aritomi Takafumi, Matsuura Takanori, Yoshimura Mitsuhiro, Ohkubo Jun-ichi, Maruyama Takashi, Kawasaki Makoto, Ohnishi Hideo, Sakai Akinori, Mizuno Atsuko, Suzuki Makoto, Ueta Yoichi
Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan; Department of Orthopaedics, Youmeikai Obase Hospital, Kanda, Fukuoka 800-0344, Japan.
Department of Orthopaedics, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
Brain Res Bull. 2015 Sep;118:7-16. doi: 10.1016/j.brainresbull.2015.08.004. Epub 2015 Aug 24.
Members of the transient receptor potential (TRP) family of ion channels play important roles in inflammation and pain. Here, we showed that both TRPV1 and TRPV4 might contribute to biphasic nocifensive behavior and neuroendocrine response following a formalin test. We subcutaneously injected saline, formalin, or the TRPV4 agonist, 4α-phorbol 12,13-didecanoate (4α-PDD) into one hindpaw of wild-type (WT), TRPV1-deficient (Trpv1(-/-)), and TRPV4-deficient (Trpv4(-/-)) mice to investigate nocifensive behaviors (phase I [0-10 min] and phase II [10-60 min]) and Fos expression in the dorsal horn of the spinal cord and other brain regions related to pain, in the paraventricular nucleus (PVN), paraventricular nucleus of the thalamus, the medial habenular nucleus, the medial nucleus of the amygdala and capsular part of the central amygdala. Subcutaneous (s.c.) injection of formalin caused less nocifensive behavior in Trpv1(-/-) and Trpv4(-/-) mice than in WT mice during phase I. In phase II, however, formalin induced less nocifensive behavior only in the Trpv1(-/-) mice, but not in the Trpv4(-/-) mice, relative to WT mice. The number of Fos-like immunoreactive (LI) neurons in laminae I-II of the dorsal horn increased in all types of mice 90 min after s.c. injection of formalin; however, there was no difference in the other regions between saline- and formalin-treated mice. Furthermore, s.c. injection of 4α-PDD did not induce nociceptive behavior nor influence the number of Fos-LI neurons in the all above mentioned regions in any of the mice. These results suggest that TRPV4-mediated nociceptive information from the peripheral tissue excluding the spinal pathway might be involved the formalin behavioral response during phase I. Only TRPV1 might regulate the formalin behavioral response in peripheral neuron.
瞬时受体电位（TRP）离子通道家族成员在炎症和疼痛中发挥重要作用。在此，我们表明TRPV1和TRPV4可能都参与了福尔马林试验后的双相伤害性防御行为和神经内分泌反应。我们将生理盐水、福尔马林或TRPV4激动剂4α-佛波醇12,13-十二烷酸酯（4α-PDD）皮下注射到野生型（WT）、TRPV1缺陷型（Trpv1(-/-)）和TRPV4缺陷型（Trpv4(-/-)）小鼠的一只后爪中，以研究伤害性防御行为（I期[0 - 10分钟]和II期[10 - 60分钟]）以及脊髓背角和其他与疼痛相关脑区（室旁核（PVN）、丘脑室旁核、内侧缰核、杏仁核内侧核和中央杏仁核被囊部）中Fos的表达。皮下（s.c.）注射福尔马林后，在I期，Trpv1(-/-)和Trpv4(-/-)小鼠的伤害性防御行为比WT小鼠少。然而，在II期，相对于WT小鼠，福尔马林仅在Trpv1(-/-)小鼠中诱导出较少的伤害性防御行为，而在Trpv4(-/-)小鼠中则没有。皮下注射福尔马林90分钟后，所有类型小鼠背角I-II层中Fos样免疫反应性（LI）神经元数量均增加；然而，在生理盐水处理组和福尔马林处理组小鼠的其他区域之间没有差异。此外，皮下注射4α-PDD在任何小鼠的上述所有区域均未诱导伤害性行为，也未影响Fos-LI神经元数量。这些结果表明，TRPV4介导的来自外周组织（不包括脊髓通路）的伤害性信息可能参与I期福尔马林行为反应。只有TRPV1可能在外周神经元中调节福尔马林行为反应。
