In the present research project, we have employed a combination of physiological, pharmacological and behavioral approaches to the study of somatosensory systems related to pain and analgesia. The activity of superficial lumbar dorsal horn neurons was studied in rats before and after application of kappa-opioid agonists to the spinal cord. The resulting changes in receptive field and neuronal responsiveness were compared to those observed in the presence of peripheral inflammation. The non-peptidergic kappa-opioid agonist U-50,488H had both facilitatory and inhibitory effects on superficial dorsal horn neurons. The facilitatory effects often coincided with expansion of receptive fields. The endogenous kappa-ligand, dynorphin, also had facilitatory effects on the receptive fields of superficial dorsal horn neurons. Similar expansions of receptive fields had been observed previously during inflammation or tissue injury. We postulated that enhanced excitability and expansion of receptive fields are related to inflammation-induced increases in dynorphin peptide. We characterized the spinal antinociceptive activity of both opioid and adrenergic agonists during hindpaw inflammation by injecting agents intrathecally and determining thermal paw withdrawal latencies. Agonists with mu-, delta- or alpha2 selective activity exhibited a leftward shift in the dose-response curve in rats with inflamed hindpaws as compared to control. The mechanism of enhanced efficacy may depend on the known synergistic action of opioid and adrenergic agonists at the spinal level.
