Central IRAK-4 kinase inhibition for the treatment of pain following nerve injury in rats.
Central IRAK-4 kinase inhibition for the treatment of pain following nerve injury in rats. Brain Behav Immun. 2020 May 18;: Authors: Pletinckx K, Krings D, Welbers A, Rider DA, Dunkern TR Abstract There is ample evidence for the role of the immune system in developing chronic pain following peripheral nerve injury. Especially Toll-like receptors (TLRs) and their associated signaling components and pro-inflammatory cytokines such as IL-1β, induced after injury, are involved in nociceptive processes and believed to contribute to the manifestation of chronic neuropathic pain states. Whereas the inhibition of the kinase function of IRAK-4, a central kinase downstream of TLRs and IL-1 receptors (IL-1Rs), seems efficacious in various chronic inflammatory and autoimmune models, it's role in regulating chronic neuropathic pain remained elusive to date. Here, we examined whether pharmacological inhibition of IRAK-4 kinase activity using PF-06650833 and BMS-986147, two clinical-stage kinase inhibitors, is effective for controlling persistent pain following nerve injury. Both inhibitors potently inhibited TLR-triggered cytokine release in human peripheral blood mononuclear cell (PBMC) as well as human and rat whole blood cultures. BMS-986147 showing favorable pharmacokinetic (PK) properties, significantly inhibited R848-triggered plasma TNF levels in a rat in vivo cytokine release model after single oral dosing. However, BMS-986147 dose dependently reversed co...
Sensory ganglionopathies (SG) are a rare heterogenous subgroup of neuropathies characterized by primary involvement of sensory neurons in dorsal root ganglions (DRGs) resulting in a distinctive clinical presentation. The onset is usually subacute or chronic with asymmetric, non –length-dependent sensory impairment and ataxia (when large-fiber neurons affected) and/or positive sensory symptoms such as burning pain, hyperesthesia and allodynia (when small-medium size neurons affected) with relatively well-preserved muscle strength.
Conclusion: SGB is effective in reducing the requirement of intraoperative propofol and fentanyl as well as decreasing opioid requirement in the postoperative period in patients with CRPS type II undergoing surgery.
Conclusion: Tetrapanax papyriferus and hederagenin relieved sciatica by reducing inflammation levels, inhibiting p38 MAPK phosphorylation, and decreasing the levels of dorsal root ganglion proteins. PMID: 32617100 [PubMed]
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]
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...
ConclusionsOur results suggest that DRGS applied with stimulation parameters within typical clinical ranges predominantly activates A β‐mechanoreceptors. In general, varying clinically controllable parameters affects the number of Aβ‐mechanoreceptors activated, although longer pulse widths can increase Aδ‐neuron activation. Our data support several Neuromodulation Appropriateness Consensus Committee guidelines on the clin ical implementation of DRGS.
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 ...
ConclusionsThis study suggests a significant, clinically relevant effect of DRG stimulation on neuropathic pain, but also demonstrates substantial problems with maintenance and revision of currently available systems. Consequently, treatment with equipment marketed specifically for DRG stimulation is currently paused in Denmark.
Conclusions: Concomitant use of bilateral SPG block with general anesthesia is an effective and safe alternative technique to scalp blockade for obtundation of hemodynamic responses due to noxious stimulus during craniotomy surgeries.
ConclusionsThese data demonstrates the possibility of sensitization of vestibular nucleus neurons to impair vestibular function after CM, and anti-CGRP treatment to restore vestibular dysfunction in patients with CM.