Suppression of neuropathic pain by selective silencing of dorsal root ganglion ectopia using nonblocking concentrations of lidocaine

Neuropathic pain is frequently driven by ectopic impulse discharge (ectopia) generated in injured peripheral afferent neurons. Observations in the spinal nerve ligation (SNL) model in rats suggest that cell bodies in the dorsal root ganglion (DRG) contribute 3 times more to the ectopic barrage than the site of nerve injury (neuroma). The DRG is therefore a prime interventional target for pain control. Since DRG ectopia is selectively suppressed with lidocaine at concentrations too low to block axonal impulse propagation, we asked whether targeted delivery of dilute lidocaine to the L5 DRG can relieve L5 SNL-induced tactile allodynia without blocking normal sensation or motor function. Results showed that intraforaminal injection of 10-µL bolus doses of 0.2% lidocaine suppressed allodynia transiently, while sustained infusion over 2 weeks using osmotic minipumps suppressed it for the duration of the infusion. Bolus injections of morphine or fentanyl were ineffective. Lidocaine applied to the cut spinal nerve end or the L4 DRG did not affect allodynia, suggesting that discharge originating in the neuroma and in neighboring “uninjured” afferents makes at best a minor contribution. Spike electrogenesis in the DRG is apparently the primary driver of tactile allodynia in the SNL model of neuropathic pain, and it can be controlled selectively by superfusing the relevant DRG(s) with nonblocking concentrations of lidocaine. This approach has potential clinical applic...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Publication date: Available online 6 September 2019Source: Anaesthesia &Intensive Care MedicineAuthor(s): G. Baranidharan, Ibrahim MohamedAbstractNeuropathic pain is a well-recognized chronic pain condition. This can have a significant impact in patients' quality of life. Neuromodulation is defined by the International Neuromodulation Society as ‘the therapeutic alteration of activity in the central or peripheral nervous system either electrically or pharmacologically’. Electrical stimulation can be performed at the motor cortex, deep brain, spinal cord, dorsal root ganglion, peripheral nerve and peripheral...
Source: Anaesthesia and intensive care medicine - Category: Anesthesiology Source Type: research
Complex regional pain syndrome (CRPS) type I and CRPS type II diminish quality of life and can lead to significant disability.15 Both conditions have varied and complex clinical features, with chronic debilitating pain being the primary symptom, usually involving the lower or upper extremities.16,24 The conditions are differentiated by the absence (CRPS-I) or presence (CRPS-II) of demonstrable nerve damage as an underlying etiology.
Source: The Journal of Pain - Category: Materials Science Authors: Source Type: research
In this study, the biological effects and mechanisms of RACK1 contributes to the pathogenesis of chronic constriction injury (CCI)-induced neuropathic pain were investigated. By western blot and staining, we found that RACK1 protein changed in dorsal root ganglion (DRG) neurons and spinal cord (SC) neurons except glial cells after CCI. Especially, RACK1 was co-located with IB4-, CGRP-positive neurons, suggesting it was related to integrate nociceptive information from the primary afferents in DRG. The successful establishment of CCI models also directly led to mechanical allodynia and heat hyperalgesia, which could be rev...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
We examined 9293 individuals from the Copenhagen General Population Study using nuclear magnetic resonance spectroscopy measurements of total cholesterol, free- and esterified cholesterol, triglycerides, phospholipids, and particle concentration. Fourteen subclasses of decreasing size and their lipid constituents were analysed: six subclasses were very low-density lipoprotein (VLDL), one intermediate-density lipoprotein (IDL), three low-density lipoprotein (LDL), and four subclasses were high-density lipoprotein (HDL). Remnant lipoproteins were VLDL and IDL combined. Mean nonfasting cholesterol concentration was 72â...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
This study, when complete, will be a monumental step-up for evidence-driven medicine in the rapidly growing field of neuromodulation,” said Andrea Trescot, the CMO of Stimwave and former President of the American Society of Interventional Pain Physicians (ASIPP). “Every other industry is expected to show efficacy through sham and placebo-controlled studies; the Tsunami study is growing the evidence that single-stage, wireless neurostimulators can offer more options to more pain patients.” Medtech's Response The opioid crisis has had a profound impact in the U.S. resulti...
Source: MDDI - Category: Medical Devices Authors: Tags: Digital Health Source Type: news
Publication date: Available online 23 July 2019Source: Neuroscience LettersAuthor(s): Yun Zou, Yumeng Cao, Yuqi Liu, Xinyi Zhang, Jinbao Li, Yuanchang XiongAbstractNeuropathic pain induced by peripheral nerve injury is a complex and chronic state that is accompanied by poor quality of life. However, whether PIM1 (proviral integration site 1) contributes to the development of nociceptive hypersensitivity induced by nerve injury remains unknown. The present study was designed to investigate the effects of PIM1 on spinal nerve ligation (SNL) induced pain hypersensitivity. Here, we found that PIM1 positive neurons in the dorsa...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
CONCLUSIONS: Dorsal root ganglion stimulation does not induce GABA release from the spinal dorsal horn cells, suggesting that the mechanisms underlying DRGS in pain relief are different from those of conventional SCS. The modulation of a GABA-mediated "Gate Control" in the DRG itself, functioning as a prime Gate of nociception, is suggested and discussed. PMID: 31334605 [PubMed - as supplied by publisher]
Source: CNS Neuroscience and Therapeutics - Category: Neuroscience Authors: Tags: CNS Neurosci Ther Source Type: research
Conclusion. We provide a molecular mechanism for the activation of pain signals based on AMPK-mTOR axis, as well as an intervention strategy by targeting AMPK-mTOR axis in LDH-induced painful radiculopathies. Level of Evidence: N/A
Source: Spine - Category: Orthopaedics Tags: BASIC SCIENCE Source Type: research
Abstract BACKGROUND: Pulsed radiofrequency (PRF) is a minimally invasive interventional technique that provides a novel and effective treatment strategy for neuropathic pain (NP). PRF is advantageous because it does not damage nerves and avoids sensory loss after treatment. At present, animal studies have demonstrated that PRF is safe and effective for relieving the NP associated with sciatic nerve damage in rats with chronic constriction injury (CCI). However, the mechanism through which this effect occurs is unknown. An increasing body of evidence shows that the expression of the P2X ligand-gated ion channel 3 (...
Source: Chinese Medical Journal - Category: General Medicine Authors: Tags: Chin Med J (Engl) Source Type: research
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