Peripheral oxytocin restores light touch and nociceptor sensory afferents towards normal after nerve injury

Oxytocin reduces primary sensory afferent excitability and produces analgesia in part through a peripheral mechanism, yet its actions on physiologically characterized, mechanically sensitive afferents in normal and neuropathic conditions are unknown. We recorded intracellularly from L4 dorsal root ganglion neurons characterized as low-threshold mechanoreceptors (LTMRs) or high-threshold mechanoreceptors (HTMRs) in female rats 1 week after L5 partial spinal nerve injury or sham control (n = 24 rats/group) before, during, and after ganglionic perfusion with oxytocin, 1 nM. Nerve injury desensitized and hyperpolarized LTMRs (membrane potential [Em] was −63 ± 1.8 mV in sham vs −76 ± 1.4 mV in nerve injury; P
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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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
Inhibition of voltage-gated calcium (CaV) channels is a potential therapy for many neurological diseases including chronic pain. Neuronal CaV1/CaV2 channels are composed of α, β, γ and α2δ subunits. The β subunits of CaV channels are cytoplasmic proteins that increase the surface expression of the pore-forming α subunit of CaV. We targeted the high-affinity protein–protein interface of CaVβ's pocket within the CaVα subunit. Structure-based virtual screening of 50,000 small molecule library docked to the β subunit led to the identification of 2-(3,5-dimethylisoxa...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
This study aimed to investigate the mechanisms underlying activation of colonic extrinsic afferent nerves and their neuronal cell bodies by a major secondary bile acid, deoxycholic acid (DCA). All experiments were performed on male C57BL/6 mice. Afferent sensitivity was evaluated using in vitroextracellular recordings from mesenteric nerves in the proximal colon (innervated by vagal and spinal afferents) and distal colon (spinal afferents only). Neuronal excitability of cultured dorsal root ganglion (DRG) and nodose ganglion (NG) neurons was examined with perforated patch clamp. Colonic 5-HT release was assessed using ELIS...
Source: American Journal of Physiology. Gastrointestinal and Liver Physiology - Category: Physiology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Neurons in the trigeminal nucleus fall into several categories based on electrophysiological properties. AbstractThe trigeminal nucleus caudalis (TNc) receives extensive afferent innervation from peripheral sensory neurons of the trigeminal ganglion (TG), and is the first central relay in the circuitry underpinning orofacial pain. Despite the initial characterization of the neurons in the superficial laminae, many questions remain. Here we report on electrophysiological properties of 535 superficial lamina I/II TNc neurons. Based on their firing pattern, we assigned these cells to five main groups, including (1) tonic, (2)...
Source: Physiological Reports - Category: Physiology Authors: Tags: Original Research Source Type: research
In this report, we identify an exon-levelcis-eQTL (rs6471859) that regulates human DRG CA8 alternative splicing, producing a truncated 1,697bp transcript (e.g., CA8-204). Our functional genomic studies show the “G” allele at rs6471859 produces a cryptic 3’UTR splice site regulating expression of CA8-204. We developed constructs to study the expression and function of the naturally occurring CA8-204G transcript (G allele at rs6471859), CA8-204C (C allele at rs6471859 reversion mutation) and CA8-201 (full length transcript). CA8-204G transcript expression occurred predominantly in non-neuronal cells (HEK293...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
Abstract Background: Pulsed radiofrequency (PRF) on the dorsal root ganglion (DRG) has been applied to alleviate neuropathic pain effectively, yet the mechanisms underlying pain reduction owing to this treatment are not clarified completely. The activated microglia, brain-derived neurotrophic factor (BDNF), phosphatidylinositol 3-kinase (PI3K), and phosphorylated extracellular signal-regulated kinase (p-ERK) in the spinal cord were demonstrated to be involved in developing neuropathic pain. Also, it has been just known that PRF on DRG inhibits the microglial activation in nerve injury rats. Here, we aim to investi...
Source: Pain Research and Management - Category: Anesthesiology Authors: Tags: Pain Res Manag Source Type: research
Impaired AMPK‑CGRP signaling in the central nervous system contributes to enhanced neuropathic pain in high‑fat diet‑induced obese rats, with or without nerve injury. Mol Med Rep. 2019 Jun 06;: Authors: Guo X, Tao X, Tong Q, Li T, Dong D, Zhang B, Zhao M, Song T Abstract Obesity is associated with increased sensitivity to pain, including neuropathic pain, but the precise mechanisms are not fully understood. Recent evidence has revealed that AMP‑activated protein kinase (AMPK) in the central nervous system (CNS) regulates the neuropeptide calcitonin gene‑related peptide (CGRP), a principal neu...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
Condition:   Neuropathic Pain Intervention:   Other: ECAPS Closed Loop SCS Sponsor:   Duke University Enrolling by invitation
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
In conclusion, the site of action of σ1R for opioid modulation on acute thermal nociception is located at the peripheral and supraspinal levels, and the opioid-potentiating effect is independent of the spinal noradrenaline increase produced by S1RA. Introduction The sigma-1 receptor (σ1R) has been described as the first ligand-regulated molecular chaperone located at the endoplasmic reticulum and plasma membranes whose activity is regulated in an agonist-antagonist manner. The σ1R is expressed in key areas for pain control and there is cumulative evidence supporting an involvement of the σ1R...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
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