Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur., México, D.F., Mexico.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., Mexico.
Pharmacol Rep. 2014 Dec;66(6):964-71. doi: 10.1016/j.pharep.2014.06.011. Epub 2014 Jun 24.
In the present study we determined the role of transient receptor potential V1 channel (TRPV1) and acid-sensing ion channel 3 (ASIC3) in chronic nociception.
1% formalin was used to produce long-lasting secondary allodynia and hyperalgesia in rats. Western blot was used to determine TRPV1 and ASIC3 expression in dorsal root ganglia.
Peripheral ipsilateral, but not contralateral, pre-treatment (-10min) with the TRPV1 receptor antagonists capsazepine (0.03-0.3μM/paw) and A-784168 (0.01-1μM/paw) prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in the ipsilateral and contralateral paws. Likewise, peripheral ipsilateral, but not contralateral, pre-treatment with the non-selective and selective ASIC3 blocker benzamil (0.1-10μM/paw) and APETx2 (0.02-2μM/paw), respectively, prevented 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Peripheral ipsilateral post-treatment (day 6 after formalin injection) with capsazepine (0.03-0.3μM/paw) and A-784168 (0.01-1μM/paw) reversed 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. In addition, peripheral ipsilateral post-treatment with benzamil (0.1-10μM/paw) and APETx2 (0.02-2μM/paw), respectively, reversed 1% formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. TRPV1 and ASIC3 proteins were expressed in dorsal root ganglion in normal conditions, and 1% formalin injection increased expression of both proteins in this location at 1 and 6 days compared to naive rats.
Data suggest that TRPV1 and ASIC3 participate in the development and maintenance of long-lasting secondary allodynia and hyperalgesia induced by formalin in rats. The use of TRPV1 and ASIC3 antagonists by peripheral administration could prove useful to treat chronic pain.
本研究旨在探讨瞬时受体电位香草酸亚型 1 通道（TRPV1）和酸敏感离子通道 3（ASIC3）在慢性痛觉过敏中的作用。
采用 1%福尔马林诱导大鼠产生长期的继发性痛觉过敏和痛觉超敏。采用 Western blot 检测背根神经节中 TRPV1 和 ASIC3 的表达。
外周同侧（但非对侧）预先给予 TRPV1 受体拮抗剂辣椒素（0.03-0.3μM/足）和 A-784168（0.01-1μM/足），可预防 1%福尔马林诱导的同侧和对侧足继发性机械性痛觉过敏和痛觉超敏。同样，外周同侧（但非对侧）预先给予非选择性和选择性 ASIC3 阻断剂苯甲脒（0.1-10μM/足）和 APETx2（0.02-2μM/足），可预防双侧足 1%福尔马林诱导的继发性机械性痛觉过敏和痛觉超敏。外周同侧（福尔马林注射后第 6 天）给予辣椒素（0.03-0.3μM/足）和 A-784168（0.01-1μM/足）可逆转双侧足 1%福尔马林诱导的继发性机械性痛觉过敏和痛觉超敏。此外，外周同侧给予苯甲脒（0.1-10μM/足）和 APETx2（0.02-2μM/足），可分别逆转双侧足 1%福尔马林诱导的继发性机械性痛觉过敏和痛觉超敏。TRPV1 和 ASIC3 蛋白在正常情况下表达于背根神经节，福尔马林注射后 1 天和 6 天，与未处理的大鼠相比，这两种蛋白在该部位的表达均增加。
数据表明，TRPV1 和 ASIC3 参与了福尔马林诱导的大鼠长期继发性痛觉过敏和痛觉超敏的发生和维持。外周给予 TRPV1 和 ASIC3 拮抗剂可能有助于治疗慢性疼痛。
