Oral application of magnesium-L-threonate alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats.

BACKGROUND: We have reported neuro-inflammation is involved in radicular pain by enhancing the efficiency of pain synaptic transmission in spinal level. Recently, peers' studies have confirmed that magnesium deficiency leads to neuro-inflammation, thus contributes to memory and emotional deficits and pain hypersensitivity in antineoplastic agents treated rats. In this study, we explore the effect of oral application of magnesium-L-threonate (L-TAMS) in radicular pain induced by lumbar disc herniation (LDH) of rats and the possible mechanisms. METHODS: Rat model of LDH was induced by autologous nucleus pulposus (NP) implantation. Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. L-TAMS was applied from drinking water at dosage of 604 mg/kg/day from 2 day before NP implantation and until the end of the experiment. Free Mg2+ content in serum and cerebrospinal fluid (CSF) was measured by calmagite chromometry. Synaptic transmission efficiency was determined by C-fiber evoked field potentials recorded by electrophysiologic recording in vivo. The activation of microglia in spinal dorsal horn was displayed by immunofluorescence staining and western blotting. The expressions of pro-inflammatory cytokines and glutamic N-methyl-D-aspartate receptor (NMDAR) subunits (NR2A, NR2B) were assessed by western blotting and enzyme-linked immunosorbent assay (ELISA) respectively. RESULTS: NP implantation induced mechanical allodynia and thermal hyperalgesia, accompanied by decreased Mg2+ concentration in serum and CSF which were both obscured by oral application of L-TAMS. L-TAMS inhibited spinal microglia activation and pro-inflammatory cytokines (TNF-α, IL-6, IL-1ß) expression of rats with NP. L-TAMS decreased C-fiber evoked potentials and NR2B protein level in rats with NP, which were rescued by extra intrathecal delivery of TNF-α or IL-6 or IL-1ß. CONCLUSIONS: Oral application of L-TAMS alleviates radicular pain by inhibiting neuro-inflammation dependent central sensitization of rats.

IL-10 alleviates radicular pain by inhibiting TNF-α/p65 dependent Nav1.7 up-regulation in DRG neurons of rats.

BACKGROUND: Lumbar disc herniation (LDH) may induce radicular pain, the upregulation of voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) contributes to radicular pain by generating ectopic discharge of neurons, but the mechanism is unclear. Previously, we reported pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) up-regulated VGSCs in diabetic neuropathy. In this study, we explored the effect of anti-inflammatory cytokine interleukin-10 (IL-10) on radicular pain and the possible mechanisms. METHODS: Rat model of LDH was induced by implanting autologous nucleus pulposus (NP). Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. IL-10 and TNF-α level in DRG and cerebrospinal fluid (CSF) were assessed by Enzyme-linked immunosorbent assay (ELISA). IL-10 was intrathecally delivered for 12 days. The expression of IL-10R1 and sodium channel Nav1.7 was displayed by immunofluorescence staining. The protein level of TNF-α and p-p65 was measured by western blotting. RESULTS: NP implantation increased Nav1.7 expression in DRG neurons, decreased IL-10 level and increased TNF-α level in DRG and CSF. IL-10 significantly alleviated pain behaviors of rats with NP. IL-10R1 was co-localized with neurons but not with satellite cells in DRG. IL-10 decreased Nav1.7 and TNF-α/p-p65 expression in DRG of rats with NP. Co-administration of TNF-α with IL-10 counteracted the effect of IL-10 on pain behaviors, Nav1.7 and TNF-α/p-p65 expression of rats with NP. CONCLUSIONS: The study revealed that IL-10 alleviated radicular pain by inhibiting TNF-α/p-p65 dependent Nav1.7 up-regulation in DRG neurons.

The Effect of Melatonin on Radicular Pain in a Rat Model of Lumbar Disc Herniation.

STUDY DESIGN: Controlled, randomized, animal study. OBJECTIVE: To investigate the effect of melatonin and its receptors on radicular pain and the possible mechanisms. SUMMARY OF BACKGROUND DATA: Lumbar disc herniation (LDH) may induce radicular pain, but the mechanism is not clear and therapeutic effect is still poor. Previously we report central sensitization meaning potentiation of spinal nociceptive synaptic transmission is the critical cause of radicular pain. Melatonin (Mel) has been reported to promote hippocampal synaptic transmission and thus improve learning ability. But the effect of Mel on spinal synaptic transmission and radicular pain are not clear. METHODS: Rat LDH model was induced by autologous nucleus pulposus (NP) implantation. Melatonin was delivered intraperitoneally four times a day, from day 1 to day 3 after surgery. Melatonin receptor agonist and antagonists were delivered intrathecally for 3 days as well. Mechanical and thermal pain thresholds were assessed by von Frey filaments and hotplate test respectively. Electrophysiological recording was employed for survey C-fiber evoked field potentials. The protein level of N- methyl-D-aspartate submit 2A (NR2A), NR2B, melatonin receptor 1 (MT1), and receptor 2 (MT2) was evaluated by western blotting. Spinal expression of calcitonin gene related peptides (CGRP), isolectin b4 (IB4), and neurofilament-200 (NF200) was displayed by immunofluorescence staining. RESULTS: Melatonin significantly increased mechanical and thermal pain thresholds, lasting at least to day 5 after surgery. Melatonin decreased C-fiber evoked field potentials; decreased spinal NR2B protein level; reduced spinal CGRP, and IB4 expression. MT2 was upregulated after NP implantation and was co-localized with neuron and microglia. MT2 receptor agonist simulated the effect of Mel, and both MT receptor broadspectrum antagonist and MT2 specific antagonist abolished the effect of MT2 receptor agonist. CONCLUSION: Melatonin alleviates radicular pain from LDH by inhibiting central sensitization via binding with its receptor 2, decreasing spinal CGRP, IB4, and NR2B expression.

Fascia lata packing and tension suturing for symptomatic pseudomeningocele after recurrent cervical intradural tumour resection.

In recurrent posterior cervical intradural tumour resections, serious complications can be developed. The dural can become affected by inflammatory factors or removed during tumor resection; if cerebrospinal fluid (CSF) leakage cannot be stopped by duraplasty, artificial meninges or fascia repair, large pseudomeningocele can develop posteriorly within the soft tissue of the neck. When the pressure of the CSF cannot be maintained steadily, persistent clinical symptoms can occur, such as postural headache or central fever. Moreover, the skin can also be penetrated in a few patients even after extension of the drainage duration, lumbar cistern drainage or skin suturing, leading to the induction of life-threatening intra-cranial infections. Is there a simple and effective surgical method to address this scenario? The aim of this study was, therefore, to investigate the effectiveness of fascia lata packing and tension suturing in the treatment of symptomatic pseudomeningocele after recurrent posterior cervical intradural tumour resection. In our study, nine consecutive spinal surgery patients were recruited from January 2008 to January 2018. All pseudomeningoceles were combined with postural headache, central neurological fever or wound non-union. There were 3 cases of melanocytoma, 3 cases of nasopharyngeal carcinoma metastasis, 2 cases of breast cancer metastasis, and 1 case of spinal canal lymphadenoma. Standard patient demographics, diagnosis, post-operative symptoms, wound healing time, and the largest pre- and last follow-up pseudomeningocele area on axial MRI sections were recorded. All cases were followed-up successfully, from 12 to 24 months, with an average of 15.3 months. Our observations indicate that all wounds healed successfully. The wound union time was 20.7 days on average. After wound union, these patients became symptom free. The largest cerebrospinal fluid area on axial MRI sections improved significantly from 42.9 ± 5.01 cm2 at p re-operation to 6.6 ± 1.89 cm2 at 1 year post-operation (P < 0.05); Our data indicate that .the proposed procedure is simple, safe and effective. And more importantly, it allows rapid closure of any cerebrospinal fluid leakage pools.

Toll-like receptor 4/nuclear factor-kappa B pathway is involved in radicular pain by encouraging spinal microglia activation and inflammatory response in a rat model of lumbar disc herniation.

BACKGROUND: Lumbar disc herniation (LDH) is a common cause of radicular pain, but the mechanism is not clear. In this study, we investigated the engagement of toll-like receptor 4 (TLR4) and the nuclear factor-kappa B (NF-κB) in radicular pain and its possible mechanisms. METHODS: An LDH model was induced by autologous nucleus pulposus (NP) implantation, which was obtained from coccygeal vertebra, then relocated in the lumbar 4/5 spinal nerve roots of rats. Mechanical and thermal pain behaviors were assessed by using von Frey filaments and hotplate test respectively. The protein level of TLR4 and phosphorylated-p65 (p-p65) was evaluated by western blotting analysis and immunofluorescence staining. Spinal microglia activation was evaluated by immunofluorescence staining of specific relevant markers. The expression of pro- and anti-inflammatory cytokines in the spinal dorsal horn was measured by enzyme linked immunosorbent assay. RESULTS: Spinal expression of TLR4 and p-NF-κB (p-p65) was significantly increased after NP implantation, lasting up to 14 days. TLR4 was mainly expressed in spinal microglia, but not astrocytes or neurons. TLR4 antagonist TAK242 decreased spinal expression of p-p65. TAK242 or NF-κB inhibitor pyrrolidinedithiocarbamic acid alleviated mechanical and thermal pain behaviors, inhibited spinal microglia activation, moderated spinal inflammatory response manifested by decreasing interleukin (IL)-1ß, IL-6, tumor necrosis factor-α expression and increasing IL-10 expression in the spinal dorsal horn. CONCLUSIONS: The study revealed that TLR4/NF-κB pathway participated in radicular pain by encouraging spinal microglia activation and inflammatory response.

SFKs/p38 Pathway is Involved in Radicular Pain by Promoting Spinal Expression of Pro-Inflammatory Cytokines in a Rat Model of Lumbar Disc Herniation.

STUDY DESIGN: A controlled, randomized, animal study. OBJECTIVE: The aim of this study was to investigate the role of src-family kinases/p38 pathway in a rat model of lumbar disc herniation (LDH). SUMMARY OF BACKGROUND DATA: LDH always generates radicular pain, and the mechanism remains unclear. We have reported that spinal src-family kinases (SFKs) may be involved in the process, but the downstream mechanism needs further investigation. METHODS: LDH was induced by implantation of autologous nucleus pulposus (NP), harvest from the tail, in lumbar 4/5 spinal nerve roots of rat. Von Frey filaments and radiant heat tests were performed to determine mechanical and thermal pain threshold respectively. Basso, Beattie, and Bresnahan (BBB) scale was assessed to test the locomotor function. The protein level of p-SFKs, t-SFKs, p-p38, t-p38 in spinal cord was examined by western blotting analysis. Cellular location of p-p38 was determined by immunochemistry staining. Spinal tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-6 levels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: Rats with NP implantation showed persistent ipsilateral mechanical allodynia and thermal hyperalgesia, which manifested as obvious decrease of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL). BBB scale indicated the locomotor function of hindpaws in rats with NP implantation kept intact. Western blotting and immunohistochemistry staining revealed that phosphorylated SFKs (p-SFKs) and phosphorylated p38 MAPK (p-p38) were sequentially upregulated in ipsilateral spinal dorsal horn, but not in contralateral side of rats with NP. Intrathecal delivery of SFKs inhibitor reduced spinal p-p38 expression. Both SFKs and p38 inhibitors alleviated pain behaviors in a dose-responsive manner without disturbing locomotor function and reduced spinal expression of TNF-α, IL-1ß, and IL-6 in rats with NP. CONCLUSION: Spinal SFKs contribute to radicular pain by activation of p38 MAPK and increasing pro-inflammatory cytokines expression in rats with NP implantation. Targeting SFKs/p38 pathway may be helpful for alleviating radicular pain. LEVEL OF EVIDENCE: N/A.

Puerarin alleviate radicular pain from lumbar disc herniation by inhibiting ERK-dependent spinal microglia activation.

Lumbar disc herniation is a common cause of radicular pain, but the mechanism remains ambiguous and the treatment stays unsatisfied. Many studies revealed a traditional Chinese medicine puerarin may moderate chronic pain from diabetes and nerve injury. Thus far, the role and mechanism of puerarin in radicular pain is still unknown. In this study, by using a rat model of lumbar disc herniation, which was induced by autologous nucleus pulposus (NP) implantation, the analgesic effect of puerarin on radicular pain was tested. Puerarin was delivered intraperitoneally form 1 h before surgery, and once daily for 7 days. The results demonstrated that NP implantation induced long-lasting pain, characterized by decrease of paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in ipsilateral hindpaws, as long as day 20 after surgery. Spinal phosphorylated extracellular signal-regulated kinase (p-ERK) was up-regulated from day 5 to day 20 after surgery in ipsilateral but not contralateral side, and p-ERK was mainly co-localized with microglia. Puerarin decreased p-ERK expression from day 7 to day 20 after surgery. Puerarin or ERK inhibitor PD98059 alleviated pain behaviors, decreased expression of microglia marker ionized calcium-binding adaptor molecule 1 (Iba-1) in rats with NP implantation. The results suggested puerarin may alleviate radicular pain by inhibiting ERK-dependent or accompanied spinal microglia activation.

Surgical treatment indications and outcomes in patients with spinal metastases in the cervicothoracic junction (CTJ).

BACKGROUND: The cervicothoracic junction (CTJ) site accounts for approximately 10% of all spinal metastases. The complex anatomical and biomechanical features increase the difficulty in surgical treatment of the CTJ metastases. However, few studies in the literature on surgical treatment for spinal metastases are focusing on this special area. The aim of this study was to evaluate the surgical outcome of patients with CTJ metastases and analyze the prognostic factor for the postoperative survival. METHODS: Total of 34 patients with CTJ metastases who underwent surgery in our department were retrospectively analyzed. We evaluated records for the details of medical history, treatment, surgery, radiographic imaging, and follow-up. Outcomes were assessed by overall survival as well as modified Tokuhashi score, SINS, Frankel grade, visual analog scale (VAS), and Karnofsky Performance Status (KPS). RESULTS: The entire patients' median survival time was 12.4 months (range, 3.5-36.2 months). Pain improved in 32 patients (94.12%), and the postoperative VAS scores were significantly improved compared with preoperative data. Majority of patients (71%) maintained or improved their Frankel scores 1 year after surgery. KPS scores improved in 13 patients (38%), remained stable in 19 (56%), and worsened in 2 (6%) postoperatively. Notably, patients with neurological deficit that did not improve after surgery had significantly worse median survival than those who had either no deficit or who improved after surgery. There were no instrumentation failures in this study. CONCLUSIONS: Surgical treatment is effective for patients of CTJ metastases, with a tolerable rate of complications. Remained or regained ambulatory status predicted overall survival. Thus, prompt and aggressive decompressive surgery is recommended for CTJ metastases patients with neurological impairment.

Src-family kinases activation in spinal microglia contributes to central sensitization and chronic pain after lumbar disc herniation.

Background Lumbar disc herniation is a major cause of radicular pain, but the underlying mechanisms remain largely unknown. Spinal activation of src-family kinases are involved in the development of chronic pain from nerve injury, inflammation, and cancer. In the present study, the role of src-family kinases activation in lumbar disc herniation-induced radicular pain was investigated. Results Lumbar disc herniation was induced by implantation of autologous nucleus pulposus, harvest from tail, in lumbar 4/5 spinal nerve roots of rat. Behavior test and electrophysiologic data showed that nucleus pulposus implantation induced persistent mechanical allodynia and thermal hyperalgesia and increased efficiency of synaptic transmission in spinal dorsal horn which underlies central sensitization of pain sensation. Western blotting and immunohistochemistry staining revealed that the expression of phosphorylated src-family kinases was upregulated mainly in spinal microglia of rats with nucleus pulposus. Intrathecal delivery of src-family kinases inhibitor PP2 alleviated pain behaviors, decreased efficiency of spinal synaptic transmission, and reduced phosphorylated src-family kinases expression. Furthermore, we found that the expression of ionized calcium-binding adapter molecule 1 (marker of microglia), tumor necrosis factor-α, interleukin 1 -ß in spinal dorsal horn was increased in rats with nucleus pulposus. Therapeutic effect of PP2 may be related to its capacity in reducing the expression of these factors. Conclusions These findings suggested that central sensitization was involved in radicular pain from lumbar disc herniation; src-family kinases-mediated inflammatory response may be responsible for central sensitization and chronic pain after lumbar disc herniation.

Surgical outcome of thoracic myelopathy caused by ossification of ligamentum flavum.

Ossification of the ligamentum flavum (OLF) may result in thoracic myelopathy (TM) because of the spinal canal narrowing. The aim of this study was to investigate clinical outcomes of symptomatic thoracic OLF treated using posterior decompressive laminectomy. We made a retrospective review of patients who underwent posterior decompressive laminectomy from 2007 through 2016 for symptomatic TM caused by OLF. Thirty-three patients who had surgery for TM caused by OLF that was diagnosed based on clinical, radiologic, and pathologic evaluations. All patients had undergone decompressive laminectomy and excision of the OLF. The clinical course was evaluated according to modified JOA scores. Magnetic resonance imaging was used to determine the number of vertebral segments demonstrating OLF, the level of thoracic cord involvement, and spine lesions coexisting with OLF. Results showed the neurological status improved at follow up (70.82±32.22months) from a preoperative mean Japanese Orthopaedic Association score of 7.03±1.29 points to 9.52±0.83 points at the last follow up (p<0.01). Recovery outcomes were excellent in 8 patients, good in 22 patients, fair in 2 patients and poor in 1 patient. Surgical complications, which resolved after appropriate and prompt treatment, including cerebrospinal fluid leakage in 4 patient, immediate postoperative neurologic deterioration in 2 patient, and wound infection in 4 patient. Our findings suggest that posterior decompressive laminectomy with or without instrumented fusion is an effective treatment for symptomatic thoracic OLF, which provides satisfactory clinical improvement.

Ideal T1 laminar screw fixation based on computed tomography morphometry.

BACKGROUND: The application of laminar screws is an alternative fixation for the first thoracic vertebra (T1). This paper is to determine the anatomical characteristics for adequate laminar screw fixation, and present a modified method of sagittal reconstruction of T1 to provide more accurate measurements. METHODS: Computed tomography (CT) images of 62 patients (32 males, 30 females) were used for the analysis. The following parameters of the T-1 lamina were measured using Mimics software: lamina length, axis angle, minimal outer cortical width, cancellous width, minimal outer cortical height, cancellous height, and spinous process height. Right or left modified sagittal reconstructions (parallel to right or left screws) were innovatively used for measurement. RESULTS: There were no significant differences between the left and right sides for each measurement performed (P > 0.05), but significant differences were detected between males and females (P < 0.05). The mean length of the T1 lamina was 32.8 mm of the T1 minimal outer cortical width was 7.4 mm, and 3.8% of males had a minimal outer cortical width < 5 mm, while 8.6% of females had a minimal outer cortical width < 5 mm. The mean minimal outer cortical height was 10.8 mm, and 1.9% of males had a minimal outer cortical height < 9 mm, while 7.7% of females had a minimal outer cortical height < 9 mm. CONCLUSION: This study suggests there are no anatomical limitations for T1 laminar screw placement in most people. The modified sagittal reconstruction method described allows for easy and precise measurement to aid in the insertion of laminar screws in T1, and gives good visualization of laminar screw insertion direction.

Ultrastructural Features of Neurovascular Units in a Rat Model of Chronic Compressive Spinal Cord Injury.

Chronic spinal cord compression is the most common cause of spinal cord impairment worldwide. Objective of this study is to assess the ultrastructural features of the neurovascular unit (NVU) in a rat model of chronic compressive spinal cord injury, 24 SD rats were divided into two groups: the control group (n = 12), and the compression group (n = 12). A C6 semi-laminectomy was performed in the control group, whereas a water-absorbent polyurethane polymer was implanted into the C6 epidural space in the compression group. The Basso Beattie Bresnahan (BBB) scores and the somatosensory evoked potentials (SEP) were used to evaluate neurological functions. Transmission Electron Microscopy (TEM) was performed to investigate the change of NVU at the 28th day after modeling. Compared with the control group, the compression group shows a significant reduction (P < 0.05) of BBB score and a significant severity (P < 0.05) of abnormal SEP. TEM results of the compression group showed a striking increase in endothelial caveolae and vacuoles; a number of small spaces in tight junctions; a significant increase in pericyte processing area and vessel coverage; an expansion of the basement membrane region; swollen astrocyte endfeet and mitochondria; and the degeneration of neurons and axons. Our study revealed that damage to NVU components occurred followed by chronic compressive spinal cord injury. Several compensatory changes characterized by thicker endothelium, expansive BM, increased pericyte processing area and vessel coverage were also observed.

Comparison of unilateral versus bilateral percutaneous kyphoplasty for the treatment of patients with osteoporosis vertebral compression fracture (OVCF): a systematic review and meta-analysis.

PURPOSE: To compare the short- and long-term clinical outcomes, operation times, restoration rate, dosage of polymethylmeth-acrylate (PMMA) injected, complications and X-rays exposure frequency between unilateral and bilateral kyphoplasty approaches for the treatment of OVCF. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Randomized or non-randomized controlled trials published up to April 2015 that compared the unilateral and bilateral PKP for the treatment of OVCF were acquired by a comprehensive search in the Cochrane Controlled Trial Register, PubMed, MEDLINE, EMBASE, Web of Science, OVID. Exclusion criteria were patients with neoplastic etiology (metastasis or myeloma), infection, neural compression syndrome, invasive and degenerative disease, traumatic fracture, re-operation, neurological deficits, significant scoliosis and spinal stenosis. The main end points included: operation times, the short- and long-term postoperative Visual Analogue Scale (VAS) scores, the short-term postoperative Oswestry Disability Index (ODI), restoration rate, dosage of PMMA injected, cement leakage, X-ray exposure frequency and postoperative adjacent-level fractures. RESULTS: A total of 8 studies involving 428 patients were included in the meta-analysis. The mean operative time was shorter in the unilateral groups compared with the bilateral groups [P < 0.05, weighted mean difference (WMD) -19.74 (-30.56, -8.92)]. There was no significant difference in the short-term postoperative VAS scores [P > 0.05, WMD 0.03 (-0.34, 0.40)], the long-term postoperative VAS scores between them [P > 0.05, WMD 0.01 (-0.42, 0.45)] and the short-term postoperative ODI [P > 0.05, WMD -0.33 (-2.36, 1.69)] between the two groups. The unilateral approaches required significantly less dosage of PMMA than the bipedicular approaches did [P < 0.05, WMD -1.56 (-1.59, -1.16)]. The restoration rate in the bilateral groups was higher than the unilateral groups [P < 0.05, WMD -7.82 (-12.23, -3.41)]. There was no significant difference in the risk ratio of cement leakage [P > 0.05, RR 0.86 (0.36, 2.06)] and postoperative adjacent-level fractures [P > 0.05, RR 0.91 (0.25, 3.26)] between the two methods. The mean X-ray exposure frequency in the unilateral groups was greater than the bilateral groups [P < 0.05, WMD -5.69 (-10.67, -0.70)]. CONCLUSIONS: A definitive verdict could not be reached regarding which approach is better for the treatment of OVCF. Although unilateral PKP was associated with shorter operative time, less X- ray exposure frequency and dosage of PMMA than bilateral PKP. There was no apparent difference in the short- and long-term clinical outcomes and complications between them. However, bilateral PKP approaches were higher than unilateral PKP in term of the restoration rate. But on account of lack of some high-quality evidence, we hold that amounts of high-quality randomized controlled trials should be required and more complications should be analysed to resolve which surgical approach is better for the treatment of OVCF in the future.

Three-dimensional alteration of cervical anterior spinal artery and anterior radicular artery in rat model of chronic spinal cord compression by micro-CT.

OBJECTIVE: To investigate the spatial and temporal changes of anterior spinal artery (ASA) and anterior radicular artery (ARA) of chronic compressive spinal cord injury on rat model by three-dimensional micro-CT. METHODS: 48 rats were divided into two groups: sham control group (n=24) and compressive spinal cord injury group (n=24). A C6 semi-laminectomy was performed in the sham control group, while a water-absorbable polyurethane polymer was implanted into C6 epidural space in the compression group. The Basso Beattie Bresnahan (BBB) score and somatosensory evoked potentials (SEP) were used to evaluate neurological function. Micro-CT scanning was used to investigate the change of ASA and ARA after perfusion at the 1th (n=6), 28th (n=6), 42th (n=6) and 70th (n=6) day of post operation. The diameter, angle-off and vascular index (VI) was measured by 3D micro-CT. RESULTS: In comparison with sham control, BBB score have a significant reduction at the 28th day (p<0.05) and abnormal SEP have a significant severity at the 28th day (p<0.05). Both of them have a significant improvement at the 70th day compared with that of the 28th day (p<0.05). VI shows the amount of microvessels reduced at the 28th day (p<0.05) and increased at the 70th day (p<0.05). The diameter and angle-off of ASA and ARA also changed significantly at the 28th, 42th, 70th day (p<0.05). CONCLUSION: There was a significant alteration of cervical anterior spinal artery and anterior radicular artery after chronic cervical spinal cord compression. Alteration of ASA and ARA may affect the vascular density of spinal cord and play an important role in neural functional change of chronic cervical spinal cord compression through 3D micro-CT.

Can Modified Kurokawa's Double-Door Laminoplasty Reduce the Incidence of Axial Symptoms at Long-term Follow-up?: A Prospective Study of 152 Patients With Cervical Spondylotic Myelopathy.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: The purpose of this study was to determine whether the modified procedure reduces long-term axial symptoms (AS) and to understand better why the AS occur. SUMMARY OF BACKGROUND DATA: Following Kurokawa's double-door laminoplasty, postoperative AS reduce the quality of life of patients with cervical spondylotic myelopathy. The etiology of AS remains unclear. Some studies report that preservation of the C7 spinous process can reduce the frequency of AS. The modified Kurokawa procedure prevents AS by preserving the semispinalis cervicis insertion in the spinous process of C2. However, it remains unclear whether the modified procedure lowers the incidence of AS in the long term (ie, >3 y). MATERIALS AND METHODS: This prospective cohort study investigated preoperative and postoperative v, cervical intervertebral range of motion, postoperative neurological recovery, neck disability index, visual analog scale, surgical cost, and time and blood loss. RESULTS: Both groups had satisfied improvement of neurological functions (P>0.05). At 3 months and 1 year after surgery, the difference in frequency between no symptoms and mild/severe symptoms was significant (traditional group, 39.06%; modified group, 20.45%) (P<0.05). Interestingly, 3 years after surgery, there were no significant between-group differences (P>0.05). CONCLUSIONS: This modified approach reduced the incidence of postoperative ASs at 3 months and 1 year after the operation; however, the between-group difference was not significantly different at the 3-year follow-up. The reason for this finding is unclear; it may indicate that the incidence of AS is caused by other factors, such as the preservation of the C7 spinous process rather than the C2 spinous process.

The role of TNF-alpha/NF-kappa B pathway on the up-regulation of voltage-gated sodium channel Nav1.7 in DRG neurons of rats with diabetic neuropathy.

Diabetic neuropathy (DN) is a common form of peripheral neuropathy, yet the mechanisms responsible for chronic pain in this disease are poorly understood. The up-regulation of the expression and function of voltage-gated sodium channel Nav1.7 has been implicated in DN, however, the exact mechanism is unclear. In the present study, we found that a proportion of streptozotocin (STZ)-treated rats suffered from mechanical allodynia and thermal hyperalgesia for a long-lasting time. Nav1.7 was up-regulated in spinal dorsal root ganglia (DRG) of rats with DN, double immunofluorescence staining showed that the increased Nav1.7 was co-localized with large and small sized neurons but not satellite glial cells. Inhibiting the synthesis of tumor necrosis factor-α (TNF-α) by thalidomide prevented DN, accompanied by strongly blocking the up-regulation of Nav1.7, TNF-α and p-nucleus factor-kappa B (p-NF-κB) in DRG. Intrathecal injection of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) significantly attenuated the pain behaviors and over-expression of Nav1.7 in DRG neurons. These data suggest that increased TNF-α may be responsible for up-regulation of Nav1.7 in DRG neurons of rats with DN, and NF-κB signal pathway is involved in this process. The findings might provide potential target for preventing diabetic neuropathy.

Systematic back muscle exercise after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients: a randomized controlled trial.

OBJECTIVE: To analyze the clinical significance of postoperative back muscle exercises after percutaneous vertebroplasty for spinal osteoporotic compression fracture patients. DESIGN: Clinical randomized controlled trials of parallel group nonpharmacologic study. SETTING: Patients practised back muscle exercises in the spinal surgery department, rehabilitation department and at their residences. SUBJECTS: Osteoporotic compression fracture patients who had undergone percutaneous vertebroplasty and processed sufficient muscle strength to participate in the training were studied. INTERVENTIONS: Patients were randomized into two groups, which were titled A and B. General postoperation therapy, including antiosteoporotic medications and education, was offered to all patients. Group B patients received additional systematic back muscle exercise. MAIN MEASURES: Both Oswestry Disability Index (ODI) and visual analogue scale (VAS) were recorded preoperatively and postoperatively at three-day, one-month, six-month, one-year and two-year follow-up. RESULTS: From January 2006 to January 2009, a total of 82 patients were assessed for eligibility, 60 patients were enrolled and randomized into two groups. Forty-two (70%) patients (20 of 30 in Group A and 22 of 30 in Group B) were successfully followed-up for two years. Systematic back muscle exercises resulted in a significant advantage in both measurements. The ODI of Group B was significantly better than Group A at the six-month, one-year and two-year follow-ups (P < 0.05). The pain level of Group B was significantly lower than in Group A at the one- and two-year follow-ups (P < 0.05). At the end of our study, the mean (SD) of the ODI in Groups A and B were 39.1 (9.14) and 23.4 (5.62); the mean (SD) of the VAS in Groups A and B were 3.4 (1.15) and 2.1 (0.84), respectively. CONCLUSIONS: Our findings suggest that the benefit of the exercises required at least six months to be observed; however, the favourable effects could last for two years. Therefore, systematic back muscle exercise should be recommended as one of the treatment guidelines for postpercutaneous vertebroplasty patients.