Modification of rat model of sciatica induced by lumber disc herniation and the anti-inflammatory effect of osthole given by epidural catheterization.

One of the most treatable causes of lower back pain and associated sciatica is lumbar disc herniation (LDH), which is characterized by rupture of the hard outer wall (annulus fibrosis) in a lumbar intervertebral disc. In the current study, we aimed to: (1) develop and characterize a rat model of sciatica induced by LDH, while introducing a novel method of epidural catheterization; (2) use this model to evaluate the effect of osthole on pain due to LDH, and (3) gain insight into the mechanisms through which osthole affects sciatica induced by LDH. The results indicate that our newly developed rat model maintained mechanical allodynia for 28 days without reduction. Moreover, cyclooxygenase-2 (COX-2) and nitric oxide synthase (NOS) were overexpressed in the associated inflammatory response, which is consistent with clinical manifestations of the disease. We then used this model to study the effect and mechanisms through which osthole affected pain due to LDH. Our study suggests that osthole is capable of reversing hyperalgesia due to LDH, potentially through modulation of activity of COX-2 and NOS, two important proteins for the exacerbation of pain due to LDH. Finally, a molecular modeling simulation showed that osthole has unique binding capabilities to both NOS and COX-2. As the model-induced mechanical hyperalgesia response was consistent, and the position of the catheter tip and the extension/spreading of the drug in the epidural space were reliable, this study developed an improved model to study remedies for sciatic pain. Moreover, our studies demonstrate that osthole may be a feasible treatment for the reduction of pain due to hyperalgesia.

Osthole, a herbal compound, alleviates nucleus pulposus-evoked nociceptive responses through the suppression of overexpression of acid-sensing ion channel 3 (ASIC3) in rat dorsal root ganglion.

BACKGROUND: Osthole (Ost), a natural coumarin derivative, has been shown to inhibit many pro-inflammatory mediators and block voltage-gated Na+ channels. During inflammation, acidosis is an important pain inducer which activates nociceptors by gating depolarizing cationic channels, such as acid-sensing ion channel 3 (ASIC3). The aim of this study was to examine the effects of Ost on nucleus pulposus-evoked nociceptive responses and ASIC3 over-expression in the rat dorsal root ganglion, and to investigate the possible mechanism. MATERIAL/METHODS: Radicular pain was generated with application of nucleus pulposus (NP) to nerve root. Mechanical allodynia was evaluated using von Frey filaments with logarithmically incremental rigidity to calculate the 50% probability thresholds for mechanical paw withdrawal. ASIC3 protein expression in dorsal root ganglions (DRGs) was assessed with Western blot and immunohistochemistry. Membrane potential (MP) shift of DRG neurons induced by ASIC3-sensitive acid (pH6.5) was determined by DiBAC(4) (3) fluorescence intensity (F.I.). RESULTS: The NP-evoked mechanical hyperalgesia model showed allodynia for 3 weeks, and ASIC3 expression was up-regulated in DRG neurons, reaching peak on Day 7. Epidural administration of Ost induced a remarkable and prolonged antinociceptive effect, accompanied by an inhibition of over-expressed ASIC3 protein and of abnormal shift of MP. Amiloride (Ami), an antagonist of ASIC3, strengthened the antinociceptive effect of Ost. CONCLUSIONS: Up-regulation of ASIC3 expression may be associated with NP-evoked mechanical hyperalgesia. A single epidural injection of Ost decreased ASIC3 expression in DGR neurons and the pain in the NP-evoked mechanical hyperalgesia model. Osthole may be of great benefit for preventing chronic pain status often seen in lumbar disc herniation (LDH).

Autologous nucleus pulposus transplantation to lumbar 5 dorsal root ganglion after epineurium dissection in rats: a modified model of non-compressive lumbar herniated intervertebral disc.

BACKGROUND: Nucleus pulposus of intervertebral discs has proinflammatory characteristics that play a key role in neuropathic pain in lumbar herniated intervertebral disc. One of the most commonly used animal models (the traditional model) of non-compressive lumbar herniated intervertebral disc is created by L4-L5 hemilaminectomy and the application of autologous nucleus pulposus to cover the left L4 and L5 nerve roots in rats. However, such procedures have the disadvantages of excessive trauma and low success rate. We proposed a modified model of non-compressive lumbar herniated intervertebral disc in which only the left L5 dorsal root ganglion is exposed and transplanted with autologous nucleus pulposus following incision of epineurium. We aimed to compare the modified model with the traditional one with regard to trauma and success rate. METHODS: Thirty Sprague-Dawley male rats were randomized into three groups: sham operation group (n = 6), traditional group (n = 12), and modified group (n = 12). The amount of blood loss and operative time for each group were analyzed. The paw withdrawal threshold of the left hind limb to mechanical stimuli and paw withdrawal latency to heat stimuli were examined from the day before surgery to day 35 after surgery. RESULTS: Compared with the traditional group, the modified group had shorter operative time, smaller amount of blood loss, and higher success rate (91.7% versus 58.3%, P < 0.05). There was no decrease in paw withdrawal latency in any group. The sham operation group had no decrease in postoperative paw withdrawal threshold, whereas the modified and traditional groups had significant reduction in paw withdrawal threshold after surgery (mechanical hyperalgesia). CONCLUSIONS: Transplantation of nucleus pulposus onto the L5 dorsal root ganglion following incision of epineurium in rats established an improved animal model of non-compressive lumbar herniated intervertebral disc with less trauma and more stable pain ethology.

Biomechanical effects of the extent of sacrectomy on the stability of lumbo-iliac reconstruction using iliac screw techniques: What level of sacrectomy requires the bilateral dual iliac screw technique?

BACKGROUND: Although both single and dual iliac screw techniques are used in spino-pelvic reconstruction following sacrectomy for treating sacral tumors, the basis for choosing between the two techniques for different instability types remains undetermined. The purpose of this study was to evaluate the effects of the extent of sacrectomy on the stability of the lumbo-iliac fixation construct using single and dual iliac screw techniques. METHODS: Nine human L2-pelvic specimens were tested for their intact condition simulated by L3-L5 pedicle screw fixation. Sequential partial sacrectomies and L3-iliac fixation using bilateral single and dual iliac screws were conducted on the same specimens as follows: under-S1 sacrectomy+single screw, under-½S1 sacrectomy+single screw, one-side sacroiliac joint resection+single screw, total sacrectomy+single screw, and total sacrectomy+dual screw. Biomechanical testing was performed on a material testing machine for evaluating the stiffness of the L3-iliac fixation construct in compression and torsion. FINDINGS: Single iliac screw technique was found to effectively restore the local stability in under-½S1 sacrectomy. However, it could not provide adequate stability for further resection of one-side sacroiliac joint in torsion and total sacrectomy in compression (P<0.05). On the other hand, dual iliac screw technique could restore the stability to the intact condition after total sacrectomy in both compression and torsion. INTERPRETATION: The single iliac screw technique for L3-iliac fixation could effectively restore the local stability for under-½S1 sacrectomy. However, for instabilities of the under-½S1 sacrectomy with one-side sacroiliac joint resection or total sacrectomy, the dual iliac screw technique should be considered.

[Evaluation of the role of combined TES-MEP and CSEP monitoring during the spinal surgery].

OBJECTIVE: To evaluate of the role of transcranial electrical stimulation motor evoked potential (TES-MEP) in combination with cortical somatosensory evoked potential (CSEP) monitoring during the spinal surgery. METHODS: TES-MEP on bilateral anterior tibial muscle and flexor hallucal brevis and CSEP on bilateral posterior tibial nerve were observed simultaneously on 293 patients during spinal surgery from July 2006 to April 2009. Intravenous anesthesia was employed in all the patients, a part of which were added low dose of sevoflurane or muscle relaxant. The results of TES-MEP, CSEP and combined monitoring were analyzed statistically. Pre-operative and post-operative motor and sensory functions of spinal cord were compared. RESULTS: Success rate of TES-MEP, CSEP and combined monitoring was 90.8%, 96.9% and 100% respectively. For the judgment of motor function of spinal cord, the sensitivity of TES-MEP and CSEP was 100% and 89.3% respectively and the specificity of 98.4% and 96.9%. The Youden index of the two methods was 0.984 and 0.862. For sensory function, the sensitivity of them was 76.7% and 93.3% respectively and the specificity of 98.7% and 98.0%. The Youden index was 0.754 and 0.913. The sensitivity of combined monitoring was 100%, with the specificity of 96.9%. The Youden index was 0.969. CONCLUSIONS: The precision of monitoring motor function of spinal cord with TES-MEP is higher than that with CSEP, however, for sensory function, CSEP is more precise. The sensitivity and precision of combined monitoring for spinal cord function were apparently better than that of unitary TES-MEP or CSEP. The combined TES-MEP and CSEP monitoring is a relatively ideal method.

[Predictive value of three surgical scoring systems for estimation of life expectancy in patients with extradural spinal metastasis].

OBJECTIVE: To evaluate the predictive values of Tokuhashi score, revised Tokuhashi score and Tomita score systems for life expectancy and treatment options in patients with spinal metastasis. METHODS: From February 1996 to January 2009, spinal operations in 104 cases with spinal metastasis were performed in our hospital. There were 65 males and 39 females, with an average of 53.4 years (median 52.5 years). To calculate AUC (area under the curve) values of Receiver Operating Characteristic (ROC) curves of three scores, and to analyze the accuracy of prediction of life expectancy. To compare the actual survival time with the expected survival time of the three scores by Kaplan-Meier method. Spearman correlation analysis was performed between the survival time and three scoring systems. RESULTS: All cases were followed-up with an average duration of 10.9 months, and 77 patients died. AUC analysis of ROC curves showed that the difference of the accuracy of the three scores was not significant. AUC in all groups of Tokuhashi Score was low, with a poor diagnostic accuracy. In the "died within 3 months" and "died within 6 months" groups of revised Tokuhashi score, the accuracy was low, while high in the other two groups. The AUC values of Tomita score in "died within 6 months" and "died within 24 months" were high, with a great diagnostic accuracy while the other two groups were low with a low diagnostic accuracy. Kaplan-Meier survival curve analysis showed that the actual survival time in all three scores was not entirely consistent with the expected survival time. Tokuhashi score and revised score were positively correlated with the survival time while that of Tomita score was negative. CONCLUSION: All the three prognosis scores in patients with spinal metastasis were closely related with survival time. The combination of Tokuhashi score and Tomita score may be applied to better predict postoperative survival prognosis and guide the surgical options for patients with spinal metastasis.

Alendronate treatment does not inhibit bone formation within biphasic calcium phosphate ceramics in posterolateral spinal fusion: an experimental study in porcine model.

BACKGROUND: Biphasic calcium phosphate (BCP) ceramics has a potential advantage as an osteoconductive matrix and has an optimal resorption rate for bone formation. Using BCP ceramics as a bone graft during spinal fusion requires osteogenesis within the material and subsequent bridging between adjacent vertebrae to provide long-term support. Bisphosphonates have been reported to prolong the process of bone healing. The influence of bisphosphonate treatment on bone formation within BCP ceramics in spinal fusion remains unknown. The aim of this study was to evaluate the influence of alendronate on BCP osteogenesis in posterolateral spinal fusion. METHODS: Posterolateral spinal fusion with pedicle screw fixation was performed at the lumbar spine in twenty-two pigs. BCP ceramics were applied as a bone graft to obtain bone fusion between adjacent transverse processes. Eleven pigs in the treatment group received oral alendronate 10 mg/d for three months postoperatively. Eleven pigs in the control group did not receive treatment with alendronate. All animals underwent posterolateral spinal fusion with BCP ceramics. The fusion rate was evaluated three months after the operation. RESULTS: The fusion rates evaluated by X-ray were 27.3% in the treatment group and 20% in the control group. The fusion rates using histological evaluation were 18.2% in the treatment group and 20% in the control group. The mean volumes of fusion mass were (3.64 +/- 0.86) cm(3) in the treatment group and (4.26 +/- 0.63) cm(3) in the control group. No significant differences were found in either trabecular bone volume or residual BCP volume between treatment and control groups using histological evaluation. The new bone formation within BCP ceramics was greater in the area adjacent to transverse process (P < 0.01). CONCLUSION: Oral alendronate with a dose of 10 mg daily do not inhibit bone formation within BCP ceramics or affect the fusion rate in posterolateral spinal fusion from porcine models.

[Estimation of life expectancy for selecting surgical procedure and predicting prognosis of extradural spinal metastases].

BACKGROUND & OBJECTIVE: Clinically, whether and how to make a surgical interventional decision for the patients with spinal metastases is still controversial. Life expectancy is a significant determinant in the selection of surgical procedure for spinal metastases. This study was to evaluate Tomita and Tokuhashi scoring systems in selecting surgical procedure and predicting prognosis of extradural spinal metastases. METHODS: A total of 169 patients with spinal metastases, treated in the Spine Unit of Aarhus University Hospital, Denmark, from Jan. 2001 to Apr. 2004, were enrolled. The life expectancy was scored according to both Tomita system and Tokuhashi system before operation, the spinal metastases were classified according to Tomita system, and the patients underwent surgery accordingly. Follow-up was done 6, 12, and 24 months after operation. The precise of Tomita system and Tokuhashi system in estimating "death within 3 months", "death within 6 months", and "death within 12 months" was compared using Receiver Operating Characteristic curves (ROC curves). The mean survival time of the patients was calculated by Kaplan-Meier method. RESULTS: ROC curves of "death within 3 months", "death within 6 months", and "death within 12 months" showed no significant difference between Tomita score and Tokuhashi score in each group (P = 0.16, P = 0.47, and P = 0.38, respectively). Kaplan-Meier survival curves showed that Tomita system overestimated the prognosis in scores from 4 to 7, and Tokuhashi system underestimated the prognosis in scores from 0 to 8. CONCLUSIONS: Both Tomita and Tokuhashi scoring systems could be used to predict prognosis of spinal metastases after operation. Tokuhashi scoring system can predict early death more accurately, which can be used to avoid major operation for these patients.