Sympathectomy attenuates excitability of dorsal root ganglion neurons and pain behaviour in a lumbar radiculopathy model

Abstract

Objectives: In order to elucidate the influence of sympathetic nerves on lumbar radiculopathy, we investigated whether sympathectomy attenuated pain behaviour and altered the electrical properties of the dorsal root ganglion (DRG) neurons in a rat model of lumbar root constriction.

Methods: Sprague-Dawley rats were divided into three experimental groups. In the root constriction group, the left L5 spinal nerve root was ligated proximal to the DRG as a lumbar radiculopathy model. In the root constriction + sympathectomy group, sympathectomy was performed after the root constriction procedure. In the control group, no procedures were performed. In order to evaluate the pain relief effect of sympathectomy, behavioural analysis using mechanical and thermal stimulation was performed. In order to evaluate the excitability of the DRG neurons, we recorded action potentials of the isolated single DRG neuron by the whole-cell patch-clamp method.

Results: In behavioural analysis, sympathectomy attenuated the mechanical allodynia and thermal hyperalgesia caused by lumbar root constriction. In electrophysiological analysis, single isolated DRG neurons with root constriction exhibited lower threshold current, more depolarised resting membrane potential, prolonged action potential duration, and more depolarisation frequency. These hyperexcitable alterations caused by root constriction were significantly attenuated in rats treated with surgical sympathectomy.

Conclusion: The present results suggest that sympathectomy attenuates lumbar radicular pain resulting from root constriction by altering the electrical property of the DRG neuron itself. Thus, the sympathetic nervous system was closely associated with lumbar radicular pain, and suppressing the activity of the sympathetic nervous system may therefore lead to pain relief.

Keywords: Dorsal root ganglion; Excitability; K+ channel; Lumbar radicular pain; Sympathectomy; Whole-cell patch-clamp.

Figs. 1a - 1b

Graphs showing the mean responses to a) mechanical stimulation, with the root constriction (RC) group showing mechanical hypersensitivity from three to 28 days post-operatively surgery, but significant reduction of hypersensitivity in the RC + sympathectomy (RC+Syx) group, and b) thermal stimulation, with the RC group showing thermal hypersensitivity from three to 28 days post-operatively, again with the hypersensitivity significantly reduced in the RC+Syx group. Mechanical hypersensitivity from three to ten days post-operatively and thermal hypersensitivity from three to 14 days post-operatively was not completely reduced compared with the control group. Error bars denote the standard error of the mean (* p < 0.05 versus control; ** p < 0.01 versus control; † p < 0.05 versus RC+Syx).

Figs. 1a - 1b

Graphs showing the mean responses to a) mechanical stimulation, with the root constriction (RC) group showing mechanical hypersensitivity from three to 28 days post-operatively surgery, but significant reduction of hypersensitivity in the RC + sympathectomy (RC+Syx) group, and b) thermal stimulation, with the RC group showing thermal hypersensitivity from three to 28 days post-operatively, again with the hypersensitivity significantly reduced in the RC+Syx group. Mechanical hypersensitivity from three to ten days post-operatively and thermal hypersensitivity from three to 14 days post-operatively was not completely reduced compared with the control group. Error bars denote the standard error of the mean (* p < 0.05 versus control; ** p < 0.01 versus control; † p < 0.05 versus RC+Syx).

Fig. 2

Bar charts showing the electrophysiological properties of the dorsal root ganglion (DRG) in the three experimental groups. The root constriction (RC) neurons exhibited lower threshold current, increased depolarised resting membrane potential (RMP), prolonged action potential duration at 50% repolarisation (APD50), and increasing depolarisation frequency (max spike count) compared with the control neurons. These hyperexcitable alterations caused by root constriction were significantly attenuated by surgical sympathectomy. There were no significant changes in any of the other parameters tested such as threshold voltage, amplitude and after hyperpolarisation (AHP) (* p < 0.05 versus control; † p < 0.05 versus RC+Syx).

Fig. 3

Example graphs showing action potentials in the short stimulation protocol. The root constriction (RC) neurons exhibited more depolarised resting membrane potential (RMP) and prolonged action potential duration at 50% repolarisation (APD₅₀) compared with the control neurons. These changes were not observed in the RC+sympathectomy (Syx) neurons that exhibited properties similar to controls.

Fig. 4

Responses of the dorsal root ganglion (DRG) neurons in the long stimulation protocol (maximum spike count). The root constriction (RC) neuron exhibited an increased number of action potential (AP) spikes and more depolarised resting membrane potential (RMP) compared with the control neurons. These hyperexcitable alterations were reduced in the RC+ sympathectomy (Syx) neurons.