The roles of substance P (SP), somatostatin (SST), calcitonin gene-related peptide (CGRP), galanin and glutamic acid, which are contained in the primary afferents, in nociceptive transmission at the spinal dorsal horn are described. In the experiments using the in situ perfusion technique in a localized area of the rabbit spinal dorsal horn and radioimmunoassay, mechanical or thermal noxious stimulation of the skin, which did not produce severe inflammation like edema, selectively increased the release of immunoreactive SP or SST into the same perfusates, respectively. Intrathecal injection of synthetic SP or SST in rats selectively produced an hyperalgesia to mechanical or thermal noxious stimulation, respectively. Intrathecal injection of antibody against SP or SST in rats, particularly in rats with inflammation, inhibited the mechanically or thermally-induced nociception, respectively. These data suggest that SP and SST separately play roles in transmission of mechanically and thermally induced nociceptive information, respectively. Furthermore, it was suggested that CGRP and galanin probably act on the capsaicin-sensitive primary afferents to increase the activated release of endogenous SP from their terminals, and consequently, processing of nociceptive information induced by mechanical stimulation of the periphery is enhanced in the spinal dorsal horn. Furthermore, our data suggest that CGRP facilitates processing of thermal nociception in the spinal dorsal horn, maybe through increasing the release of SST. On the other hand, endogenous glutamic acid probably mediates the aversive responses induced by intrathecal SP in rats.