A Depressant Action of Substance P on Spinal Nociceptive Neurons in the Rat and Cat

Neurons at many levels of the neuraxis are excited by substance P administered microelectrophoretically from multibarrelled micropipettes. In the spinal cord, the polypeptide is located in abundance in the superficial laminae, and in nonmyelinated primary afferent fibres. It is released into a perfusate on stimulation of the afferent fibres. The release is blocked by the administration of morphine. These facts have led to the hypothesis that substance P may be an excitatory neurotransmitter, released form the terminals of unmyelinated primary sensory neurons. The observation that the excitatory effects are most noticeable on neurons with an excitatory input from peripheral nociceptors has further led to the suggestion that it is an important excitatory transmitter in the pain pathway.