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Experiments with selective antagonists for the tachykinin receptors (especially NK 1 and NK2), and with knockout (KO) mice with disruptions of the genes encoding for substance P and neurokinin A or the NK 1 receptor have shown that the tachykinins play a role in nociceptive processing, especially in pain and hyperalgesia related to chemical and inflammatory stimuli. We have examined the role of the tachykinins in pain and hyperalgesia induced by chemical stimulation of viscera. We reasoned that clear identification of the functional role of the tachykinins should be simpler in the visceral system, since almost all visceral afferents (>99%) contain peptides, and a high proportion contain tachykinins.

The direct depressive effect of opioids on the transmission of nociceptive processing at the spinal level is well documented (see refs in Le Bars and Besson, 1981; Duggan and North, 1984; Yaksh and Noueihed, 1985; Zieglgansberger, 1986; Besson and Chaouch, 1987). Both pre- and postsynaptic mechanisms have been proposed as an explanation of the depressive effects of opioids on the activity of nociceptive dorsal horn neurons. Despite the lack of morphological evidence for a direct presynaptic control by enkephalinergic axo-axonic synapses, there is evidence for a presynaptic action of opioid substances (Fields et al, 1980; Jessell and Iversen, 1977; Lamotte et al, 1976; MacDonald and Nelson, 1978; Mudge et al, 1979; Sastry, 1979). In addition both electrophysiological (Barker et al, 1978; Zieglgansberger and Tulloch, 1979; Yoshimura and North, 1983) and immunocytochemical (Aronin et al, 1981; Hunt et al, 1980; Ruda, 1982; Ruda et al, 1984) investigations support postsynaptic sites of action of opioids.