Mansikka H, Shiotani M, Winchurch R, Raja S N
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Anesthesiology. 1999 Jun;90(6):1643-9. doi: 10.1097/00000542-199906000-00021.
The neurokinin-1 (NK-1) receptor and its ligand, substance P, are thought to play important roles in nociception and hyperalgesia. This study evaluated the role of the NK-1 receptor in processing noxious stimuli in normal and inflammatory states.
Behavioral responses to heat and mechanical and chemical stimuli were studied in NK-1 receptor knockout mice and wild-type control mice. Thermal nociception was evaluated by measuring paw lick or jump latencies to hot plate (52, 55, and 58 degrees C) and paw withdrawal latencies to radiant heat applied to the hind paws. Mechanical nociception was measured by von Frey monofilament applications to the hind paws. Intraplantar capsaicin-induced (10 microg/20 microl) paw licking and mechanical and heat hyperalgesia were compared in NK-1 knockout and wild-type mice.
Withdrawal responses to radiant heat (4.3+/-0.18 s for knockout and 4.4+/-0.8 s for wild-type mice) and von Frey monofilaments were similar in knockout and wild-type mice. In the hot plate test, increasing the hot plate temperature from 52 degrees C to 58 degrees C resulted in a decrease in the response latency in the wild-type mice (30.4+/-17.5 s to 15.2+/-6.8 s, P < 0.05), whereas in the knockout mice the response latencies remained constant (28.2+/-19.8 s to 29+/-15.1 s, not significant). Capsaicin-induced paw licking (14.5+/-12.8 s for knockout and 41.3+/-37.3 s for wild-type mice, P < 0.05) and mechanical and heat hyperalgesia were attenuated in the knockout mice.
NK-1 receptors contribute to the withdrawal responses to high-intensity heat stimuli and to capsaicin-induced mechanical and heat hyperalgesia.
神经激肽-1（NK-1）受体及其配体P物质被认为在伤害感受和痛觉过敏中起重要作用。本研究评估了NK-1受体在正常和炎症状态下处理伤害性刺激中的作用。
在NK-1受体基因敲除小鼠和野生型对照小鼠中研究对热、机械和化学刺激的行为反应。通过测量爪舔或跳上热板（52、55和58摄氏度）的潜伏期以及后爪接受辐射热刺激时的爪退缩潜伏期来评估热伤害感受。通过将von Frey单丝应用于后爪来测量机械伤害感受。比较了NK-1基因敲除小鼠和野生型小鼠中足底注射辣椒素（10微克/20微升）诱导的爪舔以及机械和热痛觉过敏情况。
基因敲除小鼠和野生型小鼠对辐射热（基因敲除小鼠为4.3±0.18秒，野生型小鼠为4.4±0.8秒）和von Frey单丝的退缩反应相似。在热板试验中，将热板温度从52摄氏度提高到58摄氏度导致野生型小鼠的反应潜伏期缩短（从30.4±17.5秒缩短至15.2±6.8秒，P<0.05），而基因敲除小鼠的反应潜伏期保持不变（从28.2±19.8秒至29±15.1秒，无显著差异）。基因敲除小鼠中辣椒素诱导的爪舔（基因敲除小鼠为14.5±12.8秒，野生型小鼠为41.3±37.3秒，P<0.05）以及机械和热痛觉过敏均减弱。
NK-1受体有助于对高强度热刺激的退缩反应以及辣椒素诱导产生的机械和热痛觉过敏。
