Neurokinin-1 receptors are involved in behavioral responses to high- intensity heat stimuli and capsaicin-induced hyperalgesia in mice

Background: 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. Methods: 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°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 μg/20 μl) paw licking and mechanical and heat hyperalgesia were compared in NK-1 knockout and wild- type mice. Results: 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°C to 58°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. Conclusion: NK-1 receptors contribute to the withdrawal responses to high-intensity heat stimuli and to capsaicin-induced mechanical and heat hyperalgesia.