Neurokinin A as a Transmitter of Primary Afferents Involved in Thermal Nociception

For a number of years, substance P (SP) has been an outstanding candidate for the transmitter of nociceptive primary afferents. Dorsal horn SP derives partly from small dorsal ganglion cells with fine fibres, equivalent to those likely to mediate input from cutaneous nociceptors [1]. Either electrical stimulation of cutaneous nerves at high intensities or noxious cutaneous stimulation elicit release of immunoreactive-SP from the spinal cord [2,3]. Intrathecal administration of tachykinins induces behaviour similar to responses elicited by peripheral irritation and reduce nociceptive response thresholds in some reports. Antagonistic analogues can apparently produce analgesia [4,5]. Local administration of SP, close to dorsal horn sensory neurones, generally elicit excitatory effects [6,7], although complex effects with inhibitory components have also been reported. A more appropriate site for iontophoretic administration of tachykinins, however, is the substantia gelatinosa (SG), where the relevant afferents terminate.