Resiniferatoxin (RTX) causes a uniquely protracted musculoskeletal hyperalgesia in mice by activation of TRPV1 receptors.
Resiniferatoxin (RTX) causes a uniquely protracted musculoskeletal hyperalgesia in mice by activation of TRPV1 receptors.
复制标题
DOI：
10.1016/j.jpain.2013.07.021
复制
发表时间：
2013-12
期刊：
影响因子：
4
通讯作者：
Larson, Alice A.
中科院分区：
文献类型：
--
作者：
Abdelhamid, Ramy E.;Kovacs, Katalin J.;Honda, Christopher N.;Nunez, Myra G.;Larson, Alice A.
TRPV 1受体的失活是镇痛药物开发的一种方法。然而，TRPV 1受体对每种疼痛方式产生不同的影响。由于肌肉疼痛在临床上很重要，我们比较了TRPV 1配体对肌肉骨骼伤害感受与对热和触觉伤害感受的影响。注射胃肠外，辣椒素对冯弗雷纤维反应（触觉）没有影响，但诱导了短暂的低温和痛觉过敏的甩尾（热）和握力（肌肉骨骼）测定，推测其激动剂作用在TRPV 1网站。相反，RTX产生慢性（>58天）热抗伤害感受，与其报告的TRPV 1位点脱敏能力一致。在相同的小鼠，RTX产生了短暂的低温（7小时）和长期（28天）的肌肉骨骼痛觉过敏，尽管在肌肉传入的TRPV 1受体免疫反应性降低了35.5%。一旦肌肉骨骼痛觉过敏消退，小鼠对辣椒素或RTX的痛觉过敏效应具有耐受性，而对低温的耐受性直到三次注射后才形成。SB-366791（一种TRPV 1拮抗剂）可预防但不逆转肌肉骨骼痛觉过敏，表明TRPV 1受体可启动但不维持痛觉过敏。鞘内注射，RTX仅产生短暂的肌肉骨骼痛觉过敏（2天），之后小鼠对该效应具有耐受性。TRPV 1受体的作用根据形态和组织类型而变化，例如RTX引起热抗伤害感受，肌肉骨骼痛觉过敏，并且对健康小鼠的触觉伤害感受没有影响。脊髓TRPV 1受体是缓解疼痛的潜在靶点，因为它们仅诱导短暂的肌肉骨骼痛觉过敏，随后脱敏。
Inactivation of TRPV1 receptors is one approach to analgesic drug development. However, TRPV1 receptors exert different effects on each modality of pain. Because muscle pain is clinically important, we compared the effect of TRPV1 ligands on musculoskeletal nociception to that on thermal and tactile nociception. Injected parenterally, capsaicin had no effect on von Frey fiber responses (tactile) but induced a transient hypothermia and hyperalgesia in both the tail flick (thermal) and grip force (musculoskeletal) assays, presumably by its agonistic action at TRPV1 sites. In contrast, RTX produced a chronic (>58 days) thermal antinociception, consistent with its reported ability to desensitize TRPV1 sites. In the same mice, RTX produced a transient hypothermia (7 h) and a protracted (28 day) musculoskeletal hyperalgesia in spite of a 35.5% reduction in TRPV1 receptor-immunoreactivity in muscle afferents. Once musculoskeletal hyperalgesia subsided, mice were tolerant to the hyperalgesic effects of either capsaicin or RTX while tolerance to hypothermia did not develop until after three injections. Musculoskeletal hyperalgesia was prevented but not reversed by SB-366791, a TRPV1 antagonist, indicating that TRPV1 receptors initiate but do not maintain hyperalgesia. Injected intrathecally, RTX produced only a brief musculoskeletal hyperalgesia (2 days) after which mice were tolerant to this effect. The effect of TRPV1 receptors varies depending on modality and tissue type such that RTX causes thermal antinociception, musculoskeletal hyperalgesia, and no effect on tactile nociception in healthy mice. Spinal TRPV1 receptors are a potential target for pain relief as they induce only a short musculoskeletal hyperalgesia followed by desensitization.
登录
查看更多内容
影响因子：
4.7
作者：
Abdelhamid RE;Kovacs KJ;Pasley JD;Nunez MG;Larson AA
通讯作者：
Larson AA
影响因子：
5.3
作者：
Cui, M.;Honore, P.;Faltynek, C. R.
通讯作者：
Faltynek, C. R.
DOI：
10.1186/1472-6874-5-2
发表时间：
2005-03-08
期刊：
BMC women's health
影响因子：
--
作者：
Gopinath, Preethi;Wan, Elaine;Anand, Praveen
通讯作者：
Anand, Praveen
影响因子：
3.7
作者：
Churyukanov, Maxim;Plaghki, Leon;Mouraux, Andre
通讯作者：
Mouraux, Andre
DOI：
10.1016/j.jpain.2011.03.005
发表时间：
2011-09
期刊：
The journal of pain
影响因子：
--
作者：
Bishnoi M;Bosgraaf CA;Premkumar LS
通讯作者：
Premkumar LS