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

Abstract

ObjectivesIn 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.MethodsSprague-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.ResultsIn 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.ConclusionThe 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.

Human Dorsal Root Ganglion Stimulation Reduces Sympathetic Outflow and Long-Term Blood Pressure

“…We hypothesized that blocking DRG activity with electrical stimulation would lead to a reduction in sympathetic nerve activity, in addition to its analgesic effect. This was based on our previous findings as well as studies showing that reducing peripheral efferent sympathetic activity (such as after sympathectomy) attenuates the excitability of DRG neurons ( 15 ), leading us to hypothesize that the reverse is true. It has also been shown that blocking nociception-related protein channels such as TRPV1 in the T8-L3 DRGs increases sympathetic nerve activity and consequently BP ( 16 ).…”

Progress in Sympathetically Mediated Pathological Pain

“…The concept of FM as a SMP syndrome is based on the controlled studies showing that patients with FM display signs of relentless sympathetic hyperactivity and that the pain is submissive to sympathetic blockade and is rekindled by norepinephrine (NE) injections ( 8 , 9 ). Sympathetic nervous system is also involved in non- neuropathic pain conditions such as temporomandibular disorder (TMD) ( 10 ), arthritis ( 11 ), and back pain ( 12 ).…”

Attenuation of pain behaviour by local administration of alpha‐2 adrenoceptor antagonists to dorsal root ganglia in a rat radiculopathy model

“…Neuropathic pain is believed to be caused by a functional reorganization of the sensory system and the development of neural plasticity in the peripheral and central nervous systems (von Hehn et al., ; Mulla et al., ). Previous studies have suggested the sympathetic nervous system produced the generation of chronic neuropathic pain (McLachlan et al., ; Mizuno et al., ; Xie et al., ; Tanimoto et al., ; Iwase et al., ), although it has little influence on healthy tissues. We previously reported sympathetic nerve fibre sprouting around dorsal root ganglion (DRG) myelin sheaths in a lumbar radiculopathy model (Mizuno et al., ).…”

“…We previously reported sympathetic nerve fibre sprouting around dorsal root ganglion (DRG) myelin sheaths in a lumbar radiculopathy model (Mizuno et al., ). In addition, norepinephrine (NE), which is the predominant neurotransmitter of postganglionic sympathetic neurons, enhanced the excitability of DRG neurons via α 2 ‐adrenoceptors (Tanimoto et al., ) and sympathectomy attenuated pain behaviour and excitability of DRG neurons (Iwase et al., ). These findings suggested sympathetic inputs might facilitate nociceptive transmission into the spinal cord, resulting in allodynia and hyperalgesia.…”