Pain Management Research Area, United States Army Institute of Surgical Research, JBSA Fort Sam Houston, Texas.
Department of Perioperative Medicine, Clinical Center, National Institutes of Health, Bethesda, Maryland.
Pain Med. 2017 Dec 1;18(12):2453-2465. doi: 10.1093/pm/pnw260.
Opioid-based analgesics are a major component of the lengthy pain management of burn patients, including military service members, but are problematic due to central nervous system-mediated side effects. Peripheral analgesia via targeted ablation of nociceptive nerve endings that express the transient receptor potential vanilloid channel 1 (TRPV1) may provide an improved approach. We hypothesized that local injection of the TRPV1 agonist resiniferatoxin (RTX) would produce long-lasting analgesia in a rat model of pain associated with burn injury.
Baseline sensitivities to thermal and mechanical stimuli were measured in male and female Sprague-Dawley rats. Under anesthesia, a 100 °C metal probe was placed on the right hind paw for 30 seconds, and sensitivity was reassessed 72 hours following injury. Rats received RTX (0.25 μg/100 μL; ipl) into the injured hind paw, and sensitivity was reassessed across three weeks. Tissues were collected from a separate group of rats at 24 hours and/or one week post-RTX for pathological analyses of the injured hind paw, dorsal spinal cord c-Fos, and primary afferent neuropeptide immunoreactivity.
Local RTX reversed burn pain behaviors within 24 hours, which lasted through recovery at three weeks. At one week following RTX, decreased c-Fos and primary afferent neuropeptide immunoreactivities were observed in the dorsal horn, while plantar burn pathology was unaltered.
These results indicate that local RTX induces long-lasting analgesia in a rat model of pain associated with burn. While opioids are undesirable in trauma patients due to side effects, RTX may provide valuable long-term, nonopioid analgesia for burn patients.
阿片类镇痛药是烧伤患者长期疼痛管理的主要组成部分，包括军人，但由于中枢神经系统介导的副作用而存在问题。通过靶向消融表达瞬时受体电位香草酸通道 1（TRPV1）的伤害性神经末梢的外周镇痛可能提供一种改进的方法。我们假设局部注射 TRPV1 激动剂辣椒素（RTX）将在与烧伤相关的疼痛大鼠模型中产生持久的镇痛作用。
测量雄性和雌性 Sprague-Dawley 大鼠对热和机械刺激的基线敏感性。在麻醉下，将 100°C 的金属探头置于右后爪上 30 秒，在受伤后 72 小时重新评估敏感性。大鼠接受 RTX（0.25 μg/100 μL；ipl）注入受伤的后爪，并在三周内重新评估敏感性。从另一组大鼠中收集组织，在 RTX 后 24 小时和/或一周进行受伤后爪、背根脊髓 c-Fos 和初级传入神经肽免疫反应性的病理分析。
局部 RTX 在 24 小时内逆转了烧伤疼痛行为，这种疼痛持续到三周恢复。在 RTX 后一周，观察到背角中的 c-Fos 和初级传入神经肽免疫反应性降低，而足底烧伤病理学未改变。
这些结果表明，局部 RTX 在与烧伤相关的疼痛大鼠模型中诱导持久的镇痛作用。虽然阿片类药物由于副作用而不适合创伤患者，但 RTX 可能为烧伤患者提供有价值的长期非阿片类镇痛。
