Nociceptive input after peripheral nerve injury results in cognitive impairment and alterations in primary afferent physiology in rats

In this study, we hypothesized that persistent activation of peripheral nociceptors after injury would lead to the development of a chronic pain state that impairs attention-related behavior and results in changes in peripheral neuron phenotypes. Attentional performance was measured in rats using the 5-choice serial reaction time titration variant to determine the initial impact of partial L5 spinal nerve ligation and the effect of persistent nociceptor activation on the resolution of injury. The changes in peripheral neuronal sensibilities and phenotypes were determined in sensory afferents using electrophysiologic signatures and receptive field properties from dorsal root ganglion recordings. Partial spinal nerve injury impaired attentional performance, and this was further impaired in a graded fashion by nociceptive input through an engineered surface. Impairment in attention persisted for only up to 4 days initially, followed by a second phase 7 to 10 weeks after injury in animals exposed to nociceptive input. In animals with prolonged impairment in behavior, the mechanonociceptors displayed a persistent hypersensitivity marked by decreased threshold, increased activity to a given stimulus, and spontaneous activity. Nerve injury disrupts attentional performance acutely and is worsened with peripheral mechanonociceptor activation. Acute impairment resolves, but persistent nociceptive activation produces re-emergence of impairment in the attention-related task associated wi...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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Background Dorsal root ganglion field stimulation is an analgesic neuromodulation approach in use clinically, but its mechanism is unknown as there is no validated animal model for this purpose. The authors hypothesized that ganglion stimulation is effective in reducing pain-like behaviors in preclinical chronic pain models.Methods The authors provided ganglion stimulation or spinal cord stimulation to rats with traumatic neuropathy (tibial nerve injury), or osteoarthritis induced by intraarticular knee monosodium iodoacetate, or without injury (na ïve). Analgesia was evaluated by testing a battery of pain-related ref...
Source: Anesthesiology - Category: Anesthesiology Source Type: research
We report four cases of effective analgesia for intractable secondary headache resistant to medical management with high thoracic ESP blocks. In each case, the ESP block provided instant pain relief. We suggest that the findings of this case series indicate that the ESP block may be a useful intervention in patients with severe secondary headache or posterior cervical pain where conventional therapies have limited success, though more studies are necessary. PMID: 32606918 [PubMed]
Source: Local and Regional Anesthesia - Category: Anesthesiology Tags: Local Reg Anesth Source Type: research
Conditions:   Low Back Pain;   Pain Measurement;   Chronic Pain;   Analgesia, Epidural;   Clinic, Pain Interventions:   Procedure: Fluoroscopically guided lumbar medial branch nerve radiofrequency denervation.;   Procedure: Fluoroscopically guided lumbar facet joint injection.;   Procedure: Fluoroscopically guided lumbar epidural corticosteroid injection.;   Procedure: Fluoroscopically guided caudal epidural c orticosteroid injection.;   Procedure: Fluoroscopically guided pulsed radiofrequency of the lumbar dorsal root ganglion.;   Procedu...
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
AbstractObjectivesTraumatic peripheral nerve injuries (PNI) often result in severe neuropathic pain which typically becomes chronic, is recalcitrant to common analgesics, and is associated with sleep disturbances, anxiety, and depression. Pharmacological treatments proven to be effective against neuropathic pain are not well tolerated due to side effects. Neuromodulative interventions such as peripheral nerve or spinal cord stimulation have generated mixed results and may be limited by reduced somatotopic specificity. Dorsal root ganglion (DRG) stimulation may be more effective in this etiology.Materials and MethodsTwenty ...
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Clinical Research Source Type: research
Authors: Heijmans L, Joosten EA Abstract Tonic spinal cord stimulation (SCS) has been used as a treatment for chronic neuropathic pain ever since its discovery late 1960's. Despite its clinical successes in a subset of chronic neuropathic pain syndromes, several limitations such as insufficient pain relief and uncomfortable paresthesias, have led to the development of new targets, the dorsal root ganglion, and new stimulation waveforms, such as burst and high frequency. The aim of this review is to provide a brief overview of the main mechanisms behind the mode of action of the different SCS paradigms. Tonic SCS ma...
Source: Postgraduate Medicine - Category: Internal Medicine Tags: Postgrad Med Source Type: research
AbstractPurposeEvaluation of clinical and radiological effects of the therapeutic outcome of CT-guided pulsed radiofrequency (PRF) treatment adjacent to the lumbar dorsal root ganglion (DRG) for patients with chronic intractable lumbosacral radicular pain in a single-center prospective longitudinal study in order to evaluate predictive factors of safety and therapeutic success.Materials and methodsThirty patients, from 2016 to 2018, were enrolled (age: 42 –80 aa, 66.7% men and 33.3% females) with low back pain, lumbosciatalgia and/or lumbocruralgia, resistant to previous medical and physical treatments for a period not 
Source: La Radiologia Medica - Category: Radiology Source Type: research
BackgroundDorsal root ganglion stimulation (DRG ‐S) is a novel approach to treat chronic pain. Lead placement at L2 has been reported to be an effective treatment for axial low back pain (LBP) primarily of discogenic etiology. We have recently shown, in a diverse cohort including cases of multilevel instrumentation following extensive prior bac k surgeries, that DRG‐S lead placement at T12 is another promising target. Local effects at the T12 DRG, alone, are insufficient to explain these results.Materials and MethodsWe performed a literature review to explore the mechanisms of LBP relief with T12 DRG ‐S.FindingsBranc...
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Review Article Source Type: research
Toll-like receptor 7 contributes to neuropathic pain by activating NF-κB in primary sensory neurons. Brain Behav Immun. 2020 Mar 20;: Authors: He L, Han G, Wu S, Du S, Zhang Y, Liu W, Jiang B, Zhang L, Xia S, Jia S, Hannaford S, Xu Y, Tao YX Abstract Toll like receptor 7 (TLR7) is expressed in neurons of the dorsal root ganglion (DRG), but whether it contributes to neuropathic pain is elusive. We found that peripheral nerve injury caused by ligation of the fourth lumbar (L4) spinal nerve (SNL) or chronic constriction injury of sciatic nerve led to a significant increase in the expression of TLR7...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
ConclusionsDRG and SCS are cost ‐effective treatments for chronic pain secondary to CRPS‐I and II compared to CMM. DRG accrued higher cost due to higher conversion from trial to permanent implant and shorter battery life, but DRG was the most beneficial therapy due to more patients receiving permanent implants and experiencing higher quality of life compared to SCS. New DRG technology has improved battery life, which we expect to make DRG more cost‐effective compared to both CMM and SCS in the future.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Clinical Research Source Type: research
This study aimed to test the hypothesis that miR‐34c‐5p can modulate neuropathic pain in rat models with chronic constriction injury (CCI) of sciatic nerve,via interaction with the SIRT1/STAT3 signaling pathway Firstly, SIRT1 was validated as a target gene of miR ‐34c‐5p and could be negatively regulated by miR‐34c‐5p. We induced miR‐34c‐5p overexpression/inhibition, SIRT1 knockdown, and STAT3 knockdown in the model rats to assess pain behavior patterns. Meanwhile, dorsal root ganglion (DRG) was transduced with overexpression or knockdown of miR‐ 34c‐5p or lipopolysaccharide to induce the production of ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research
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