PRIMARY AFFERENT TACHYKININS ARE REQUIRED TO EXPERIENCE MODERATE TO INTENSE PAIN

The excitatory neurotransmitter glutamate coexists,vith the peptide kn own as substance P in primary afferents that respond to painful stimul ation(1). Because blockers of glutamate receptors reliably reduce pain behaviour(2-4), it is assumed that 'pain' messages are mediated by gl utamate action on dorsal horn neurons, The contribution of substance P , however, is still unclear, We have now disrupted the mouse preprotac hykinin A gene (PPT-A), which encodes substance P and a related tachyk inin, neurokinin A (ref. 5). We find that although the behavioural res ponse to mildly painful stimuli is intact in these mice, the response to moderate to intense pain is significantly reduced. Neurogenic infla mmation, which results from peripheral release of substance P and neur okinin A (ref. 6), is almost absent in the mutant mice. We conclude th at the release of tachykinins from primary afferent pain-sensing recep tors (nociceptors) is required to produce moderate to intense pain.