Increase in the number of NADPH-diaphorase-positive neurons in the lumbar dorsal root ganglia following lipopolysaccharide exposure of the sciatic nerve.

In the spinal cord, nitric oxide pathways are involved in hyperalgesia, and nitric oxide synthase, the enzyme responsible for its synthesis, is upregulated following several noxious and lesion stimuli. Since the histochemical reaction for NADPH-diaphorase colocalizes with NOS, we decided to study the effects of infusion of bacterial lipopolysaccharides close to the sciatic nerve on the expression of NADPH-d in the dorsal root ganglia and spinal cord of the rat. The percentage of NADPH-d-positive neurons in the L4 dorsal root ganglia increased 7-10 times on the treated side of LPS-treated rats (12.5-17.5%, compared to 0.5-2.5% of control side), whereas sham operation had no effects. The cross-sectional area of NADPH-d-positive neuronal profiles in all the dorsal root ganglia considered was consistently smaller than that of those which were negative to the histochemical reaction. In animals treated with LPS the NADPH-d-positive neurons were significantly (p = 0.02) smaller on the treated side (520 +/- 100 microns) than on the control one (679 +/- 135 microns), whereas those which were negative were of similar sizes on the two sides (1170 +/- 256 microns on the treated side vs 1214 +/- 371 microns on the control side). On the contrary, in control animals, there were no differences between untreated and sham operated sides, but differences between the sizes of NADPH-d-positive and negative neurons persisted. Therefore, LPS treatment on the sciatic nerve upregulates NADPH-d expression in the corresponding dorsal root ganglion, thus indicating an increased rate of NO production. Moreover, NADPH-d is upregulated mainly in small sized neurons, thus suggesting that it may be related with pain transmission.