1. We recorded from centrally connected axons isolated from the proximal stump of the sciatic nerve in intact rats and in rats whose nerves had been transected 4 days-6 mo previously. Afferent axons selected for study had spontaneous impulse activity that originated ectopically in dorsal root ganglia (DRGs) L4 and L5. The sympathetic supply of these DRGs was excited by repetitive electrical stimulation of ventral roots T13 and L1. We examined quantitatively changes in afferent ongoing firing evoked by sympathetic stimulation. Results are based on observations from 161 neurons in rats with sciatic nerve injury and from 58 neurons in control rats with intact sciatic nerves. Of these 219 neurons, 204 had myelinated fibers (A neurons) and 15 had unmyelinated fibers (C neurons), on the basis of measurements of conduction velocity. 2. In rats with nerve injury the majority of the spontaneously active neurons tested (95 of 161) responded to sympathetic stimulation with a change in ongoing firing frequency: 41 neurons exhibited a significant increase in discharge frequency that was often followed by suppression (28 of 41), and 54 neurons responded with a decrease in ongoing activity (simple suppression). In control rats, in contrast, only 1 of the 58 spontaneously active sensory neurons tested responded to sympathetic stimulation. 3. In A neurons, the response pattern changed systematically with time after sciatic nerve injury. At 4-22 days after nerve lesion, excitation was much more common than suppression. At 60-93 days, excitation and suppression occurred about equally. At 110-171 days, suppression was by far the more common response. 4. Of the 14 C neurons, 2 were excited by sympathetic stimulation (at 4-22 days postoperative) and 10 were suppressed (2 at 4-22 days, 8 at > 60 days). The only spontaneously active C neuron found in control rats was not affected by sympathetic stimulation. 5. The magnitude of responses in the three postoperative intervals investigated was similar. This was so for both the excitatory and the simple suppressive responses. The average latency between onset of stimulation and excitatory responses in afferent A fibers (approximately 10 s) was significantly less than the latency to simple suppressive responses (approximately 20 s). 6. The mean spontaneous firing rate of A neurons decreased with time after nerve lesion. No change was observed in C neuron activity. The mean firing rate of A neurons was significantly higher than that of C neurons 4-93 days after nerve lesion, but not later. In all three postoperative periods investigated, the mean rate of spontaneous activity was the same in A neurons that responded to sympathetic stimulation and A neurons that did not. 7. The results show that nerve injury triggers sympathetic-sensory coupling within rat DRGs. Excitatory coupling is preferentially present in the period shortly after nerve injury, and is subsequently replaced by suppressive coupling. This suggests that there is a gradual change in the underlying coupling mechanism.
Macrophage-derived HMGB1 contributes to the accelerated neurite outgrowth in dorsal root ganglion neurons isolated from the mice subjected to sciatic nerve injury
