Katsumasa Tanimoto

Transient receptor potential ankyrin 1 in spinal cord dorsal horn is involved in neuropathic pain in nerve root constriction rats

BackgroundLumbar radicular pain is categorized as a type of neuropathic pain, but its pathophysiological mechanisms are not fully understood. The substantia gelatinosa (SG) in the spinal cord dorsal horn receives primary afferent inputs and is considered to be a therapeutic target for treating neuropathic pain. In vivo patch-clamp recording is a useful procedure for analyzing the functional properties of synaptic transmission in SG neurons. Transient receptor potential ankyrin 1 (TRPA1) has been widely identified in the central and peripheral nervous systems, such as in the peripheral nociceptor, dorsal root ganglion, and spinal cord dorsal horn and is involved in synaptic transmission of pain. However, its functional role and mechanism of pain transmission in the spinal cord dorsal horn are not well understood. The purpose of this study was to use in vivo patch-clamp analysis to examine changes in the excitatory synaptic transmission of SG neurons treated with TRPA1 antagonist and to clarify the potential role of TRPA1 in the rat spinal cord dorsal horn.ResultsThe rats with root constriction (RC) showed mechanical hypersensitivity, hyperalgesia, and thermal hyperalgesia. In addition, pin pricks elicited pain-related behavior even in the sham and naïve rats. These pain-related behaviors were significantly attenuated by intrathecal injection of a TRPA1 antagonist. The degrees of intrathecal injection efficacy were equivalent among the 3 groups (RC, sham, and naïve groups). In an electrophysiological study, the frequencies and amplitudes of excitatory postsynaptic currents (EPSCs) were significantly increased in the RC rats compared with those in the sham and naïve rats. Spontaneous EPSCs and evoked-EPSCs by non-noxious and noxious stimuli were significantly decreased by TRPA1 antagonist. As in the behavioral study, there were no statistically significant differences among the 3 groups.ConclusionThese data showed that the TRPA1 antagonist had an inhibitory effect on mechanical hypersensitivity and hyperalgesia as well as on physiological pain transmission in the spinal cord dorsal horn. This suggests that TRPA1 is consistently involved in excitatory synaptic transmission even in the physiological state and has a role in coordinating pain transmission.

Changes in synaptic transmission of substantia gelatinosa neurons in a rat model of lumbar radicular pain revealed by in vivo patch-clamp recording.

&NA; Little is known about the pathophysiological mechanisms of radicular pain. We investigated changes in synaptic transmission of substantia gelatinosa (SG) neurons after an injury to the L5 nerve root using in vivo patch‐clamp recording. A total of 141 SG neurons were recorded at L4 and L5 segmental levels of the spinal cord in root constriction rats and sham‐operated control rats. At L4 and L5 segmental levels, SG neurons without a receptive field were observed only in root constriction rats, and the frequencies of spontaneous action potential firings in SG neurons were higher in the root constriction group than in the control group. At the L5 segmental level, the frequencies and amplitudes of spontaneous excitatory postsynaptic currents (EPSCs) as well as the proportion of multireceptive neurons among SG neurons was higher in the root constriction group than in the control group. At the L4 segmental level, the frequencies and amplitudes of spontaneous EPSCs were increased in the root constriction group, but the proportions of cell types did not change. The mean amplitudes of EPSCs evoked by mechanical stimuli at L4 and L5 segmental levels were larger in the root constriction group than in the control group. The results indicated that injuring the nerve root led to characteristic excitatory synaptic transmission in SG neurons at each segmental level and changed sensory processing in SG neurons at the segment to which the injured nerve projected. These changes could lead to spontaneous pain, mechanical allodynia, and hyperalgesia contributing to the pathogenesis of radicular pain. Injuring the nerve root led to characteristic excitatory synaptic transmission and changed sensory processing in substantia gelatinosa neurons in the rat spinal dorsal horn.

Microendoscopy-assisted muscle-preserving interlaminar decompression for lumbar spinal stenosis: clinical results of consecutive 105 cases with more than 3-year follow-up.

Study Design. A retrospective review of data collected prospectively on patients who underwent microendoscopy-assisted muscle-preserving interlaminar decompression (MILD) for lumbar spinal stenosis. Objective. To evaluate the clinical results including surgical invasiveness and reduction rate of facet joint with a follow-up of more than 3 years. Summary of Background Data. Hatta et al reported microscopic posterior decompression procedure, MILD for lumbar spinal stenosis with reference to the cervical central approach put forth by Shiraishi. Mikami et al applied spinal microendoscopy to MILD procedure (microendoscopy-assisted MILD). Methods. One hundred five consecutive patients, who underwent microendoscopy-assisted MILD, participated in this study. Operative time, blood loss, visual analogue scale (VAS), serum creatine kinase and C-reactive protein, surgical complications, reduction rate of the facet joint, Japanese Orthopaedic Association score, and Short-Form 36 were evaluated. Results. The operative time was 99.3 minutes and the intraoperative bleeding was 15.7 mL on average. The mean VAS score to assess surgical site pain was 20.6 mm on postoperative day 1. The mean serum creatine kinase on postoperative day 1 and C-reactive protein on postoperative day 3 were 145.4 IU/L and 2.7 mg/dL, respectively. Surgical complications were identified in 2 cases, cauda equina injury and dural tear. The mean reduction rate of the facet joint was 3%. The follow-up rate was 83.3% and the mean follow-up period was 52.7 months. The Japanese Orthopaedic Association score improved significantly from 14.8 to 23.7 points on average. Significant improvements in Short-Form 36 were observed in all subscales except in General Health. Revision surgical procedures were performed in 8 cases at the operated level including 4 of juxtafacet cyst, 3 of disc herniation, and 1 of insufficient decompression. Conclusion. Microendoscopy-assisted MILD is a minimally invasive procedure and favorable clinical results can be expected for lumbar spinal stenosis. Level of Evidence: 4

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

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.

Atypical fungal vertebral osteomyelitis in a tsunami survivor of the Great East Japan Earthquake.

Study Design. Case report. Objective. We report a rare case of fungal vertebral osteomyelitis in a tsunami survivor of the Great East Japan Earthquake. Summary of Background Data. Fungal vertebral osteomyelitis due to Scedosporium apiospermum (S. apiospermum) is extremely rare. We describe the case of a 45-year-old male who developed vertebral osteomyelitis by S. apiospermum 1 month after near drowning in the huge tsunami after the Great East Japan Earthquake. Methods. The patient was treated with a combination of percutaneous posterolateral endoscopic debridement and antifungal therapy. The case was evaluated with radiography and computed tomography, and his white blood cell count and C-reactive protein level in serum were measured 20 months after initiation of treatment. Results. The patient had no low back pain and both white blood cell count and C-reactive protein had remained normal. Radiographs and computed tomography of lumbar spine demonstrated sclerotic change of endplates and spur formation bridging the L3 and L4 vertebral bodies. Conclusion. We report a rare case of the fungal vertebral osteomyelitis caused by S. apiospermum. If a patient develops severe back pain after a near-drowning episode in dirty water such as a swamp or a river, the clinician should be suspicious of the possibility of fungal spondylitis by S. apiospermum. Level of Evidence: N/A

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

There were several reports suggesting α‐adrenoceptor antagonists are effective to treat neuropathic pain. The aims of this study were as follows: (1) to introduce drug delivery system for dorsal root ganglion (DRG) neurons; (2) to elucidate the effects of α‐adrenoceptor antagonists in acute, subacute or chronic phase and (3) to determine which subtype of adrenoceptor was mainly involved.

Sympathectomy and Sympathetic Blockade Reduce Pain Behavior Via Alpha-2 Adrenoceptor of the Dorsal Root Ganglion Neurons in a Lumbar Radiculopathy Model.

Study Design. Animal experimental study with intervention. Objective. We investigated whether sympathectomy and pharmacological sympathetic blockade reduced pain behavior and reversed adrenoceptor mRNA expression of the dorsal root ganglion (DRG) in a lumbar radiculopathy model. Summary of Background Data. The abnormal sympathetic-somatosensory interaction may underlie some forms of neuropathic pain. There are several reports that sympathectomy and pharmacological sympathetic blockades are often effective to treat neuropathic pain. However, its pathophysiological mechanisms remain obscure. Methods. We used 91 male Sprague-Dawley rats. Just after root constriction (RC), the rats underwent sympathectomy or received 3 local injections of subtype-specific &agr;-adrenergic receptor antagonists around the DRG. We evaluated the analgesic effects of sympathectomy and sympathetic blockade using behaviors indicative mechanical allodynia and thermal hyperalgesia. We estimated the mRNA expression levels of the DRG adrenoceptor subtypes using real time reverse transcription polymerase chain reaction. Results. Sympathectomy and &agr;2-antagonist significantly reduced the mechanical allodynia and thermal hyperalgesia after RC. Real time reverse transcription polymerase chain reaction analysis indicated that sympathectomy possibly reversed &agr;2A- and &agr;2B-adrenoceptors mRNA overexpression in the DRG after RC. Conclusion. We considered that pain behaviors of neuropathic pain are due, at least in part, to enhanced sympathetic noradrenergic transmission within the DRG. Suppression of sympathetic activity by reducing adrenergic release, &agr;2-adrenoceptor stimulation, and/or &agr;2-adrenoceptor upregulation in the DRG may relieve neuropathic pain. Level of Evidence: 3

The difference in gender affects the pathogenesis of ligamentum flavum hypertrophy

Introduction Gender differences may play a role in the pathogenesis of lumbar spinal stenosis. However, few reports that discuss the effects of gender differences in ligamentum flavum (LF) hypertrophy have been published, and no study has investigated the relationship between LF thickness and the quantitative value of intervertebral disc (IVD) degeneration. This study aimed to investigate the impact of gender on the pathomechanisms underlying LF hypertrophy, focusing on the relationship among LF thickness, IVD degeneration, and age. Methods The subjects include 100 patients with low back pain and leg numbness, tingling, or pain. We measured LF thickness and the T2 values of IVDs using MR imaging and analyzed the relationship among LF thickness, T2 values of IVDs, and age. The interclass correlation coefficient (ICC) was calculated as the inter-rater reliability between the LF thickness values measured by two investigators. Results ICC was calculated for the two measurements of LF thickness (r = 0.923, 95% CI: 0.907-0.936). No statistically significant difference in the T2 values of IVDs was observed between females and males from L2/3 to L5/S. There were significantly negative linear correlations between LF thickness and the T2 values of IVDs at all levels, but this correlation was not observed in females at L4/5. There were significantly negative linear correlations between age and the T2 values of IVDs from L2/3 to L5/S for all patients, females, and males (r = 0.422-0.756). In addition, there were significantly positive linear correlations between age and LF thickness from L2/3 to L4/5 for all patients (r = 0.329-0.361) and females (r = 0.411-0.481). Correlations were not observed for males at all levels or for all patients at L5/S. Conclusions The relationships identified among LF thickness, age, and IVD degeneration suggest that gender differences play a role in the pathogenesis of LF hypertrophy.

Differentiating spinal intradural-extramedullary schwannoma from meningioma using MRI T2 weighted images

OBJECTIVE: Prior studies advocate the subjective visual differences between meningioma and schwannoma on T2 weighted images, however objective measurement of signal intensity differences may be useful in certain cases. The aim of this study was to investigate whether an objective evaluation of SIs on T2 weighted images would be useful to differentiate spinal schwannomas from meningiomas. METHODS: The patients with spinal MRIs demonstrating path proven and subsequently treated intradural extramedullary spinal tumors were selected between April 2008 and May 2017. Regions of interest (ROIs) were measured in the tumor and subcutaneous fat on the same image, and we calculated the SI ratio between tumor and fat ROIs. RESULTS: Twenty patients each with meningioma and schwannoma were enrolled. The SI ratios of schwannomas were significantly higher than those of meningiomas (both researcher 1 and 2: p = 0.002). The areas under the curve by researchers 1 and 2 were 0.780. The cutoff value of SI ratio by both of researchers 1 and 2 to differentiate between schwannomas from meningiomas was 0.420 (sensitivity: 80.0%, specificity: 70.0-75.0%). CONCLUSION: The SI ratio, calculated from the SIs of the tumor and fat on T2 weighted images, is useful for differentiating spinal schwannomas from meningiomas to obtain an accurate diagnosis. ADVANCES IN KNOWLEDGE: Signal intensity ratio of the spinal tumor and fat on T2 weighted images is useful for differentiating schwannomas from meningiomas to obtain an accurate diagnosis.

Long-Term Outcome of Microendoscopic Diskectomy for Lumbar Disk Herniation. A Clinical Study of Consecutive 112 Cases with More than 5-Year Follow-Up

Background Clinical results and recurrence rate after microendoscopic diskectomy (MED) with long‐term follow‐up is still unclear, in spite of its relatively long history. Materials and Methods A total of 112 who underwent MED participated in this study. Operative time, blood loss, serum C‐reactive protein (CRP), creatine kinase (CK), and visual analog scale (VAS) were evaluated as indexes of surgical invasiveness. The 36‐Item Short Form Survey Instrument (SF‐36), Japanese Orthopaedic Association (JOA) score, patient satisfaction, and recurrence were also evaluated with a follow‐up of at least 5 years. Results The mean operative time was 86.7 minutes, and the mean blood loss was 35.7 mL. The mean CRP on postoperative day 3 and CK on the first postoperative day was 0.72 mg/dL and 224.6 IU/L, respectively, and VAS to assess surgical site pain on the first postoperative day was 24.9 mm on average. The improvement rate in the JOA score was 68.7%. The physical component summary of SF‐36 in norm‐based scoring was improved from 23.4 to 48.6. Overall, 90.8% of patients evaluated their response to the surgery as extremely satisfied or satisfied. The recurrence rate was 10.5%, and reoperation was performed in 7.9% of patients. Conclusions MED is a technique that offers both reduced invasiveness and good long‐term clinical results.