Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates.
Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates.
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DOI：
10.1186/1744-8069-6-94
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发表时间：
2010-12-17
期刊：
影响因子：
3.3
通讯作者：
Iadarola MJ
中科院分区：
文献类型：
--
作者：
Mitchell K;Bates BD;Keller JM;Lopez M;Scholl L;Navarro J;Madian N;Haspel G;Nemenov MI;Iadarola MJ
用强效辣椒素类似物树脂毒素 (RTX) 消融表达 TRPV1 的伤害性纤维，可实现持久的疼痛缓解。 RTX 特别适合局部应用，并且诱导的化学轴突病导致镇痛，其持续时间受剂量、给药途径和纤维再生速率的影响。 TRPV1 在无髓鞘 C 纤维和轻髓鞘 Adelta 纤维亚群中表达，它们分别在低和高有害加热速率下检测皮肤温度的变化。在这里，我们研究了 RTX 诱导的外周轴突病变后使用红外激光刺激的纤维类型特定行为、其恢复时间过程以及轴突损伤和伤害感受的分子相关性。将 RTX 注射到大鼠后爪（足底中部）以产生热痛觉减退。使用红外二极管激光器以小直径（1.6 毫米）、高能量、100 毫秒脉冲刺激爪子中的 Adelta 纤维，或以宽直径（5 毫米）、长持续时间、低能量脉冲刺激 C 纤维。我们监测行为反应以表明纤维的损失和再生。在注射部位，在注射 5 或 50 ng RTX 后两周内，对 C 纤维刺激的反应显着减弱。在最高强度刺激下，对 Adelta 刺激的反应在两周内显着减弱，在强度较低的 Adelta 刺激下，反应持续 5 周。对脚趾（注射远端部位）的刺激显示，5 ng RTX 后 7-8 周或 50 ng RTX 后 9-10 周，Adelta 反应显着减弱。相比之下，RTX 后 5 周时，对 C 纤维刺激的反应基本表现出正常反应。在纤维损失和恢复期间，当行为最大程度减弱时，神经再生分子标记物（ATF3和甘丙肽）在背根神经节（DRG）中上调，但伤害感受活性标记物（脊髓中的c-Fos和DRG中的MCP-1）尽管在RTX治疗后立即诱导，但恢复正常。外周 RTX 治疗后的行为恢复与表达 TRPV1 的 Adelta 和 C 纤维的再生以及分子标记的持续表达有关。红外激光刺激是评估 Adelta 纤维在疼痛和疼痛控制中的行为作用的潜在有价值的工具。
Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C- and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy. RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7- 8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal. Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control.
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影响因子：
5.5
作者：
BELMONTE, C;GALLAR, J;REBOLLO, I
通讯作者：
REBOLLO, I
影响因子：
2.9
作者：
Jeon, Sang-Min;Lee, Kyung-Min;Cho, Hee-Jung
通讯作者：
Cho, Hee-Jung
影响因子：
20.1
作者：
KAUFMAN, MP;IWAMOTO, GA;MITCHELL, JH
通讯作者：
MITCHELL, JH
影响因子：
7.4
作者：
Bates BD;Mitchell K;Keller JM;Chan CC;Swaim WD;Yaskovich R;Mannes AJ;Iadarola MJ
通讯作者：
Iadarola MJ
影响因子：
7.4
作者：
DANNEMAN, PJ;KIRITSYROY, JA;CASEY, KL
通讯作者：
CASEY, KL