Articles: neuralgia.
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Dual leucine zipper kinase (DLK) is a member of mitogen-activated protein kinase kinase kinase (MAP3K) family mainly involved in neuronal degeneration. However, the role of DLK signaling in the neuropathic pain has not yet been fully determined. Chronic constrictive injury (CCI) was conducted by four 3-0 chromic gut ligatures loosely ligated around the sciatic nerve. ⋯ In CatWalk gait analysis, significant decreases of print area, maximum contact maximum intensity, stand phase, single stance, and regular index by CCI were alleviated by the DLK shRNA administration. In conclusion, the expression of DLK was up-regulated in chronic constrictive injury and attenuated by the administration of DLK shRNA, which paralleled the improvement of neurobehavior of neuropathic pain. The modulation of DLK expression is a potential clinic treatment option for neuropathic pain.
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Randomized Controlled Trial Multicenter Study
Efficacy of the Nav1.7 blocker PF-05089771 in a randomised, placebo-controlled, double-blind clinical study in subjects with painful diabetic peripheral neuropathy.
The effect of PF-05089771, a selective, peripherally restricted Nav1.7 sodium channel blocker on pain due to diabetic peripheral neuropathy was investigated in a randomised, placebo and active-controlled parallel group clinical trial (NCT02215252). A 1-week placebo-run in the period was followed by a 4-week treatment period and a 1-week placebo run-out/taper-down period. Single-blind placebo was administered throughout run-in and run-out periods. ⋯ As predefined efficacy criteria were not met, the study did not proceed to the second part. PF-05089771 was well tolerated. Possible reasons for the modest efficacy observed with PF-05089771 are discussed.
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Randomized Controlled Trial Multicenter Study
Long-term quality of life improvement for chronic intractable back and leg pain patients using spinal cord stimulation: 12-month results from the SENZA-RCT.
Chronic axial low-back pain is a debilitating disorder that impacts all aspects of an afflicted individual's life. Effective, durable treatments have historically been elusive. Interventional therapies, such as spinal cord stimulation (SCS), have shown limited efficacy at best. Recently, a novel treatment, 10 kHz SCS, has demonstrated superior pain relief compared with traditional SCS in a randomized controlled trial (RCT). In this manuscript, we report on the long-term improvements in quality of life (QoL) outcomes for subjects enrolled in this study. ⋯ In addition to superior pain relief, 10 kHz SCS provides long-term improvements in quality of life and functionality for subjects with chronic low-back and leg pain.
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We have recently reported that a short course of morphine, starting 10 days after sciatic chronic constriction injury (CCI), prolonged the duration of mechanical allodynia for months after morphine ceased. Maintenance of this morphine-induced persistent sensitization was dependent on microglial reactivity and Toll-like receptor 4 signaling. ⋯ The efficacy of miR-124 and miR-146a were comparable, and in both cases allodynia returned within hours to days of miRNA dosing conclusion. Our findings demonstrate that miRNAs targeting Toll-like receptor signaling are effective in reversing neuropathic pain, which underscores the clinical potential of these non-coding RNAs.
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The treatment of neuropathic pain resulting from nervous system malfunction remains a challenging problem for doctors and scientists. The lower effectiveness of conventionally used analgesics in neuropathic pain is associated with complex and not fully understood mechanisms of its development. Undoubtedly, interactions between immune and nervous system are crucial for maintenance of painful neuropathy. ⋯ This review discusses the role of chemokines from all four subfamilies as essential mediators of neuron-glia interactions occurring under neuropathic pain conditions. Based on available data, we analyse the influence of chemokines on opioid properties. Finally, we identify new direct and indirect pharmacological targets whose modulation may result in effective therapy of neuropathic pain, possibly in combination with opioids.