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

Summary Statement. TRPA1 antagonist reduced spontaneous excitatory postsynaptic currents of substantia gelatinosa neuron in spinal cord dorsal horn by in vivo patch-clamp analysis. TRPA1 may act as a mediator of excitatory synaptic transmission. Introduction. Little is known about the pathophysiological mechanisms of radicular pain. The substantia gelatinosa (SG) in the spinal cord dorsal horn receives primary afferent inputs, which predominantly convey nociceptive sensations. Nociceptive information is modified and integrated in the SG, suggesting that the SG may be a therapeutic target for treating radicular pain. Electrophysiological study using in vivo patch-clamp recording from SG neurons is a useful method to analyze functional properties in synaptic transmission. Transient receptor potential ankyrin 1 (TRPA1) has been widely identified in the central and peripheral nervous system such as peripheral nociceptor, dorsal root ganglion (DRG), and spinal cord dorsal horn, and is considered that they are involved in synaptic transmission of pain. However, it is still unknown about its functional role and mechanism of pain transmission in spinal cord dorsal horn. The purpose of this study is to investigate changes in excitatory synaptic transmission of SG neurons with TRPA1 antagonist and to clarify the potential role of TRPA1 in the rat spinal cord dorsal horn using in vivo patch-clamp analysis. Methods. Male Sprague-Dawley rat were divided into three experimental groups. In the root constriction (RC) group, the right L5 spinal root was ligated proximal to the DRG. The root was exposed only in the sham operation group, and no procedure was performed in the control group. In order to evaluate the excitability of the substantia gelatinosa neuron in the dorsal horn, we recorded excitatory postsynaptic currents (EPSCs) using in vivo whole-cell patch-clamp methods in each groups. Also, to clarify the function of TRPA1, we observed the change of EPSCs with application of TRPA1 antagonist (HC030031). Statistical significance was determined as P < 0.05 using Student's paired t test and one-way analysis of variance (ANOVA) followed by a Tukey–Kramer test. Results. Spontaneous EPSCs (sEPSCs) were increased in the RC group more than in the sham and control group. With application of HC030031, the frequency and amplitude of sEPSCs were significantly reduced in all three groups. The relative frequency and the relative amplitude were 81% and 89% in the RC group, 81% and 94% in the control group, 70% and 88% in the sham group, respectively. There was no statistical significant difference among the three groups. Discussion. The mechanism of synaptic transmission via TRPA1 in the spinal cord dorsal horn is considered that activated TRPA1 cause Ca. 2+. influx into presynaptic terminal and glutamate release from synaptic vesicle onto SG neuron. In the present study, sEPSCs were significantly reduced by TRPA1 antagonist not only in the RC group but also in the control group and sham group, which indicating that some TRPA1 were activated consistently in the rat spinal cord dorsal horn. It is considered that TRPA1 act as a mediator of excitatory transmission, thus, suppressing the activity of TRPA1 may lead to pain relief