ALTERED NOCICEPTION, ANALGESIA AND AGGRESSION IN MICE LACKING THE RECEPTOR FOR SUBSTANCE-P

The peptide neurotransmitter substance P modulates sensitivity to pain by activating the neurokinin-1 (NK-1) receptor, which is expressed by discrete populations of neurons throughout the central nervous system (1-4). Substance P is synthesized by small-diameter sensory 'pain' fib res(5), and release of the peptide into the dorsal horn of the spinal cord following intense peripheral stimulation(6) promotes central hype rexcitability and increased sensitivity to pain(7-10). However, despit e the availability of specific NK-1 antagonists(4), the function of su bstance P in the perception of pain remains unclear Here we investigat e the effect of disrupting the gene encoding the NK-1 receptor in mice , We found that the mutant mice were healthy and fertile, but the char acteristic amplification ('wind up') and intensity coding of nocicepti ve reflexes was absent, Although substance P did not mediate the signa lling of acute pain or hyperalgesia, it was essential for the full dev elopment of stress-induced analgesia and for an aggressive response to territorial challenge, demonstrating that the peptide plays an unexpe cted role in the adaptive response to stress.