Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect experienced by cancer patients receiving treatment with paclitaxel. The voltage-gated sodium channel 1.7 (Na_v1.7) plays an important role in multiple preclinical models of neuropathic pain and in inherited human pain phenotypes, and its gene expression is increased in dorsal root ganglia (DRGs) of paclitaxel-treated rats. Hence, the potential of change in the expression and function of Na_v1.7 protein in DRGs from male rats with paclitaxel-related CIPN and from male and female humans with cancer-related neuropathic pain was tested here. Double immunofluorescence in CIPN rats showed that Na_v1.7 was upregulated in small DRG neuron somata, especially those also expressing calcitonin gene-related peptide (CGRP), and in central processes of these cells in the superficial spinal dorsal horn. Whole-cell patch-clamp recordings in rat DRG neurons revealed that paclitaxel induced an enhancement of ProTx II (a selective Na_v1.7 channel blocker)-sensitive sodium currents. Bath-applied ProTx II suppressed spontaneous action potentials in DRG neurons occurring in rats with CIPN, while intrathecal injection of ProTx II significantly attenuated behavioral signs of CIPN. Complementarily, DRG neurons isolated from segments where patients had a history of neuropathic pain also showed electrophysiological and immunofluorescence results indicating an increased expression of Na_v1.7 associated with spontaneous activity. Na_v1.7 was also colocalized in human cells expressing transient receptor potential vanilloid 1 and CGRP. Furthermore, ProTx II decreased firing frequency in human DRGs with spontaneous action potentials. This study suggests that Na_v1.7 may provide a potential new target for the treatment of neuropathic pain, including chemotherapy (paclitaxel)-induced neuropathic pain.SIGNIFICANCE STATEMENTThis work demonstrates that the expression and function of the voltage-gated sodium channel Na_v1.7 are increased in a preclinical model of chemotherapy-induced peripheral neuropathy (CIPN), the most common treatment-limiting side effect of all the most common anticancer therapies. This is key as gain-of-function mutations in human Na_v1.7 recapitulate both the distribution and pain percept as shown by CIPN patients. This work also shows that Na_v1.7 is increased in human DRG neurons only in dermatomes where patients are experiencing acquired neuropathic pain symptoms. This work therefore has major translational impact, indicating an important novel therapeutic avenue for neuropathic pain as a class.

OBJECT: High-grade malignant spinal cord compression is commonly managed with a combination of surgery aimed at removing the epidural tumor, followed by spinal stereotactic radiosurgery (SSRS) aimed at local tumor control. The authors here introduce the use of spinal laser interstitial thermotherapy (SLITT) as an alternative to surgery prior to SSRS. METHODS: Patients with a high degree of epidural malignant compression due to radioresistant tumors were selected for study. Visual analog scale (VAS) scores for pain and quality of life were obtained before and within 30 and 60 days after treatment. A laser probe was percutaneously placed in the epidural space. Real-time thermal MRI was used to monitor tissue damage in the region of interest. All patients received postoperative SSRS. The maximum thickness of the epidural tumor was measured, and the degree of epidural spinal cord compression (ESCC) was scored in pre- and postprocedure MRI. RESULTS: In the 11 patients eligible for study, the mean VAS score for pain decreased from 6.18 in the preoperative period to 4.27 within 30 days and 2.8 within 60 days after the procedure. A similar VAS interrogating the percentage of quality of life demonstrated improvement from 60% preoperatively to 70% within both 30 and 60 days after treatment. Imaging follow-up 2 months after the procedure demonstrated a significant reduction in the mean thickness of the epidural tumor from 8.82 mm (95% CI 7.38–10.25) before treatment to 6.36 mm (95% CI 4.65–8.07) after SLITT and SSRS (p = 0.0001). The median preoperative ESCC Grade 2 was scored as 4, which was significantly higher than the score of 2 for Grade 1b (p = 0.04) on imaging follow-up 2 months after the procedure. CONCLUTIONS: The authors present the first report on an innovative minimally invasive alternative to surgery in the management of spinal metastasis. In their early experience, SLITT has provided local control with low morbidity and improvement in both pain and the quality of life of patients.

BACKGROUND:. Although surgery followed by radiation effectively treats metastatic epidural compression, the ideal surgical approach should enable fast r

OBJECT: Spinal metastases account for the majority of bone metastases from thyroid cancer. The objective of the current study was to analyze a series of consecutive patients undergoing spinal surgery for thyroid cancer metastases in order to identify factors that influence overall survival. METHODS: The authors retrospectively reviewed the records of all patients who underwent surgery for spinal metastases from thyroid cancer between 1993 and 2010 at the University of Texas MD Anderson Cancer Center. RESULTS: Forty-three patients met the study criteria. Median overall survival was 15.4 months (95% CI 2.8–27.9 months) based on the Kaplan-Meier method. The median follow-up duration for the 4 patients who were alive at the end of the study was 39.4 months (range 1.7–62.6 months). On the multivariate Cox analysis, progressive systemic disease at spine surgery and postoperative complications were associated with worse overall survival (HR 8.98 [95% CI 3.46–23.30], p < 0.001; and HR 2.86 [95% CI 1.30–6.31], p = 0.009, respectively). Additionally, preoperative neurological deficit was significantly associated with worse overall survival on the multivariate analysis (HR 3.01 [95% CI 1.34–6.79], p = 0.008). Conversely, preoperative embolization was significantly associated with improved overall survival on the multivariate analysis (HR 0.43 [95% CI 0.20–0.94], p = 0.04). Preoperative embolization and longer posterior construct length were significantly associated with fewer and greater complications, respectively, on the univariate analysis (OR 0.24 [95% CI 0.06–0.93] p = 0.04; and OR 1.24 [95% CI 1.02–1.52], p = 0.03), but not the multivariate analysis. CONCLUSIONS: Progressive systemic disease, postoperative complications, and preoperative neurological deficits were significantly associated with worse overall survival, while preoperative spinal embolization was associated with improved overall survival. These factors should be taken into consideration when considering such patients for surgery. Preoperative embolization and posterior construct length significantly influenced the incidence of postoperative complications only on the univariate analysis.

Metastatic involvement of the spine is a common complication of systemic cancer progression. Surgery and external beam radiotherapy are palliative treatment modalities aiming to preserve neurological function, control pain and maintain functional status. More recently, with development of image guidance and stereotactic delivery of high doses of conformal radiation, local tumor control has improved; however recurrent or radiation refractory disease remains a significant clinical problem with limited treatment options. This manuscript represents a narrative overview of novel targeted molecular therapies, chemotherapies, and immunotherapy treatments for patients with breast, lung, melanoma, renal cell, prostate, and thyroid cancers, which resulted in improved responses compared to standard chemotherapy. We present clinical examples of excellent responses in spinal metastatic disease which have not been specifically documented in the literature, as most clinical trials evaluate treatment response based on visceral disease. This review is useful for the spine surgeons treating patients with metastatic disease as knowledge of these responses could help with timing and planning of surgical interventions, as well as promote multidisciplinary discussions, allowing development of an individualized treatment strategy to patients presenting with widespread multifocal progressive disease, where surgery could lead to suboptimal results.