Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain
Heat hyperalgesia after incision requires TRPV1 and is distinct from pure inflammatory pain
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DOI：
10.1016/j.pain.2005.03.010
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发表时间：
2005-06-01
期刊：
影响因子：
7.4
通讯作者：
Raja, SN
中科院分区：
文献类型：
--
作者：
Pogatzki-Zahn, EM;Shimizu, I;Raja, SN
术后疼痛显着影响患者的康复。然而，术后疼痛管理仍然不理想。也许是因为治疗策略主要基于使用炎性疼痛模型的研究。我们使用最近开发的切口痛小鼠模型来研究外周和脊柱机制，导致切口后热痛觉过敏，涉及 TRPV1 KO 小鼠的行为实验表明，正如之前在炎症模型中观察到的那样。 TRPV1 对于切口后热（而非机械）痛觉过敏是必需的。然而，在 WT 小鼠中，直到切口后 4 天，DRG 中 TRPV 免疫反应性神经元的比例和坐骨神经中 TRPV1 染色的强度均与对照小鼠没有差异。该结果通过对受到切口的大鼠坐骨神经的免疫印迹分析得到证实。与大鼠后爪炎症后坐骨神经TRPV1表达水平增加的情况不同。在没有热暴露的情况下，切开的 TRPV1 KO 和 WT 小鼠的脊髓 c-Fos 染色相似。然而，切开后热暴露的 TRPV1 KO 和 WT 小鼠之间 c-Fos 染色的差异表明，切口介导的热诱发脊髓信号传导增强涉及 TRPV1 依赖性机制。最后，与通过 NMDA 受体介导的炎症性痛觉过敏不同，切口后的热痛觉过敏可通过脊髓非 NMDA 受体的拮抗作用逆转。因此，TRPV1对于切口后热痛觉过敏的产生很重要。我们的观察表明，所有实验性疼痛模型可能并不同样适合指导术后疼痛治疗的开发。 (c) 2005 年国际疼痛研究协会。由 Elsevier B.V. 出版。保留所有权利。
Postoperative pain significantly impacts patient recovery. However, Postoperative pain management remains Suboptimal. perhaps because treatment strategies are based mainly on Studies using inflammatory pain models. We Used a recently developed mouse model of incisional pain to investigate peripheral and spinal mechanism,, contributing to heat hyperalgesia after incision, Behavioral experiments involving TRPV1 KO mice demonstrate that, as previously observed in inflammatory models. TRPV1 is necessary for heat (but not mechanical) hyperalgesia after incision. However, in WT mice, neither the proportion of TRPV immunoreactive neurons in the DRG nor the intensity of TRPV1 staining in the sciatic nerve was different from that in control.,, up to 4 days after incision. This result was corroborated by immunoblot analysis of sciatic nerve in rats subjected to an incision. and is distinct from that following inflammation of the rat hind paw, a situation in which TRPV1 expression levels in sciatic nerve increases. In the absence of heat exposure, spinal c-Fos staining was similar between incised TRPV1 KO and WT mice. However, differences in c-Fos staining between heat exposed TRPV1 KO and WT mice after incision suggest that the incision-mediated enhancement of heat-evoked signaling to the spinal cord involves a TRPV1-dependent mechanism. Finally, heat hyperalgesia after incision was reversed by antagonism of spinal non-NMDA receptors, unlike inflammatory hyperalgesia, which is mediated via NMDA receptors. Thus, TRPV1 is important for the generation of thermal hyperalgesia after incision. Our observations suggest that all experimental pain models may not be equally appropriate to guide the development of postoperative pain therapies. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.