Spinal mechanisms underlying persistent pain and referred hyperalgesia in rats with an experimental ureteric stone

Spinal neurons processing information from the ureter have been characterized in rats 1-4 days after the implantation of an experimental ureteric stone and compared with those of normal rats. The effects of a conditioning noxious stimulation of the ureter in the presence of the hyperalgesia evoked by the calculosis also were examined. Extracellular recordings were performed at the T12-L1 segments of the spinal cord. In rats with calculosis, more neurons expressed a ureter input (53 vs. 42% in normal rats); such cells being more likely to show background activity, at a higher rate than normals (6.6 +/- 1.2 vs. 3.2 +/- 0.9 spikes/s; mean +/- SE) and increasing with the continuing presence of the stone. The threshold pressure for a ureteric response was higher than in normal rats (79 +/- 5 vs. 54 +/- 4 mmHg) but the neurons failed to encode increasing intensities of stimulation. Thirty-five percent of the neurons with exclusively innocuous somatic receptive fields had a ureter input in rats with calculosis, whereas none were seen in normal rats. A noxious ureteric distention applied to neurons with ureter input evoked a complex mixture of increases and decreases in somatic receptive field size and/or somatic input properties markedly different from the generalized increases in excitability seen when such a stimulus was applied to normal animals. We conclude that the presence of a ureteric stone evokes excitability changes of spinal neurons (enhanced background activity, greater number of ureter-driven cells, decreased threshold of convergent somatic receptive fields), which likely account for the referred hyperalgesia seen in rats with calculosis. However, further noxious visceral input occurring in the presence of persistent hyperalgesia produces selective changes that cannot be explained by a generalized excitability increase and suggest that the mechanisms underlying maintenance of hyperalgesia include alteration of both central inhibitory and excitatory systems.