INHIBITION OF HYPERALGESIA BY ABLATION OF LAMINA-I SPINAL NEURONS EXPRESSING THE SUBSTANCE-P RECEPTOR

Substance P is released in the spinal cord in response to painful stim uli, but its role in nociceptive signaling remains unclear, When a con jugate of substance P and the ribosome-inactivating protein saporin wa s infused into the spinal cord, it was internalized and cytotoxic to l amina I spinal cord neurons that express the substance P receptor. Thi s treatment left responses to mild noxious stimuli unchanged, but mark edly attenuated responses to highly noxious stimuli and mechanical and thermal hyperalgesia. Thus, lamina I spinal cord neurons that express the substance P receptor play a pivotal role in the transmission of h ighly noxious stimuli and the maintenance of hyperalgesia.