Maturation of NK1 receptor involvement in the nociceptive response to formalin

Administration of NK1 antagonists in adult animals attenuates the nocicepti ve response in the formalin test, indicating that the neurokinins and the N K1 receptor play a role in mediating this pain response. The number and dis tribution of NK1 receptors change dramatically during development, and the age at which they become involved in pain processing is not known. We exami ned the role of NK1 receptors in the formalin model in rats ranging in age between 3- and 21-days old. An NK1 antagonist, CP99,994, and its less activ e enantiomer CP100,263 were administered to the spinal cord (intrathecal), systemically (subcutaneous), or locally (intraplantar). Intrathecal adminis tration of CP99,994, but not CP100,263, attenuated pain behaviors in the se cond phase of the formalin response in 14-day and 21-day old rats, but did not alter the pain response in 3-day or 10-day old rats. CP99,994 also redu ced the expression of the c-fos protein in the superficial dorsal horn of 2 1-day old rats. Systemic and intraplantar injection of either CP99,994 or C P100,263 reduced the pain response to formalin in S-day and 21-day old rats , suggesting a non-NK1 mediated mechanism of action. These results indicate that, within the spinal cord, NK1 receptors start to play a role in the pa in response to formalin between 10 and 21 days. Moreover, analgesia induced by systemic or local injection of NK1 antagonists involves mechanisms othe r than, or in addition to, the NK1 receptor. Synapse 36:254-266, 2000. (C) 2000 Wiley-Liss, Inc.