Spontaneous activity of axotomized afferent neurons after L5 spinal nerve injury in rats

TLDR

Peripheral nerve injury can cause axotomized afferent neurons to develop spontaneous activity, potentially triggering abnormal pain behavior in rats and neuropathic pain in humans. We recorded ectopic activity from L5 dorsal root afferent fibers at multiple time points after L5 spinal nerve lesion to assess the impact of sympathectomy. Ectopic activity emerged within days after L5 spinal nerve lesion, peaked at 3–8 days (≈7.3 imp/s with 41.6 % bursting), then declined to ≈3.4 imp/s by 20–53 days; sympathectomy modestly reduced bursting frequency but did not alter overall discharge rates, activity was confined to A‑fibers, and the ectopic activity positively correlated with allodynia-like behavior.

Abstract

After mechanical injury of a peripheral nerve some axotomized afferent neurons develop spontaneous activity, which is thought to trigger abnormal pain behavior in rats and neuropathic pain in humans. Here, we analysed the ectopic activity in axotomized afferent fibers recorded from the L5 dorsal root in different time periods after L5 spinal nerve lesion and the effects of sympathectomy on it. The following results were obtained: (1) Up to 6 hours after spinal nerve transection there was almost no spontaneous activity in axotomized afferents, except short-lasting injury discharges at the time of transection; (2) Three to 8 days following spinal nerve lesion, the rate of spontaneous activity was 7.3±7.7 imp/s (mean±SD, median 5.0 imp/s, n=204); 41.6% of the spontaneously active afferent neurons exhibited a bursting pattern with interspike intervals of 32.4±18.3 ms; (3) Twenty to 53 days after nerve lesion the rate of spontaneous activity had decreased significantly to 3.4±4.3 imp/s (median 2.6 imp/s, n=120). The frequency of bursting and non-bursting neurons remained roughly the same; (4) In sympathectomized rats, 15–45 days following spinal nerve lesion, the mean discharge rate was 3.8±4.3 imp/s (median 2.3 imp/s, n=255). However, the percentage of bursting neurons and the intraburst frequency decreased significantly; (5) Spontaneous activity occurred in afferent A-fibers but not in afferent C-fibers. These results suggest that ectopic activity in axotomized afferent neurons develops within the first days after L5 spinal nerve lesion, decreases with time and is only marginally dependent on the sympathetic innervation. There was a positive correlation between this ectopic activity and the allodynia-like behavior in spinal nerve-lesioned rats.