Articles: neuropathic-pain.
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Randomized Controlled Trial
Repetitive Transcranial Magnetic Stimulation for phantom limb pain in landmine victims: A double-blinded, randomized, sham-controlled trial.
We evaluated the effects of repetitive transcranial magnetic stimulation (rTMS) in the treatment of phantom limb pain (PLP) in land mine victims. Fifty-four patients with PLP were enrolled in a randomized, double-blinded, placebo-controlled, parallel group single-center trial. The intervention consisted of real or sham rTMS of M1 contralateral to the amputated leg. rTMS was given in series of 20 trains of 6-second duration (54-second intertrain, intensity 90% of motor threshold) at a stimulation rate of 10 Hz (1,200 pulses), 20 minutes per day, during 10 days. For the control group, a sham coil was used. The administration of active rTMS induced a significantly greater reduction in pain intensity (visual analogue scale scores) 15 days after treatment compared with sham stimulation (-53.38 ± 53.12% vs -22.93 ± 57.16%; mean between-group difference = 30.44%, 95% confidence interval, .30-60.58; P = .03). This effect was not significant 30 days after treatment. In addition, 19 subjects (70.3%) attained a clinically significant pain reduction (>30%) in the active group compared with 11 in the sham group (40.7%) 15 days after treatment (P = .03). The administration of 10 Hz rTMS on the contralateral primary motor cortex for 2 weeks in traumatic amputees with PLP induced significant clinical improvement in pain. ⋯ High-frequency rTMS on the contralateral primary motor cortex of traumatic amputees induced a clinically significant pain reduction up to 15 days after treatment without any major secondary effect. These results indicate that rTMS is a safe and effective therapy in patients with PLP caused by land mine explosions.
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Electrical neuromodulation by spinal cord stimulation (SCS) is a well-established method for treatment of neuropathic pain. However, the mechanism behind the pain relieving effect in patients remains largely unknown. In this study, we target the human cerebrospinal fluid (CSF) proteome, a little investigated aspect of SCS mechanism of action. ⋯ Previously unknown effects of SCS on levels of proteins involved in neuroprotection, nociceptive signaling, immune regulation, and synaptic plasticity are demonstrated. These findings, in the CSF of neuropathic pain patients, expand the picture of SCS effects on the neurochemical environment of the human spinal cord. An improved understanding of SCS mechanism may lead to new tracks of investigation and improved treatment strategies for neuropathic pain.
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Molecular neurobiology · Aug 2016
Interleukin-17A Acts to Maintain Neuropathic Pain Through Activation of CaMKII/CREB Signaling in Spinal Neurons.
Immunity and neuroinflammation play major roles in neuropathic pain. Spinal interleukin (IL)-17A, as a mediator connecting innate and adaptive immunity, has been shown to be an important cytokine in neuroinflammation and acute neuropathic pain. However, the effects and underlying mechanisms of spinal IL-17A in the maintenance of neuropathic pain remain unknown. ⋯ Furthermore, we showed that blocking CaMKII with KN93 significantly reduced SNL- or rIL-17A-induced hyperalgesia and p-CREB expression. Our in vitro data showed that KN93 also significantly inhibited rIL-17A-induced CREB activation in primary cultured spinal neurons. Taken together, our study indicates that astrocytic IL-17A plays important roles in the maintenance of neuropathic pain through CaMKII/CREB signaling pathway in spinal cord, and thus targeting IL-17A may offer an attractive strategy for the treatment of chronic persistent neuropathic pain.
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Previous studies have demonstrated that tumor necrosis factor-alpha (TNF-α) in the red nucleus (RN) plays a facilitated role in the development of neuropathic pain, and its effect is transmitted through TNF-α receptor (TNFR) subtypes 1 and 2. Here, the dynamic distributions of TNF-α and TNFRs in the RN of rats with spared nerve injury (SNI) were investigated. Western blot analysis and immunofluorescence staining indicated that TNF-α was hardly expressed in the RN of normal rats but significantly increased at 1 week and peaked at 2 weeks after SNI. ⋯ A low level of TNFR2 was expressed in the RN of normal rats, but it was significantly increased at 1 week and 2 weeks after SNI and localized in neurons and all three types of glia. These findings suggest that neurons and three types of glia in the RN all contribute to TNF-α production and participate in the initiation and/or maintenance of neuropathic pain induced by SNI. TNF-α exerts its effects in different types of cells maybe through different receptors, TNFR1 and/or TNFR2, in the different stages of neuropathic pain.
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Randomized Controlled Trial
Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.
Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study (NCT01954927), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis. ⋯ This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies.