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

Background: The neurokinin-l (NK-I) 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 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 mu g/20 mu l) pam licking and mechanical and heat hyperalgesia were compared in NK-1 knockout and mild-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 degrees C to 58 degrees C resulted in a decrease in the response latency in the mild-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 mere 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.