The CCL2 elevation in primary afferent fibers produces zymosan-induced hyperalgesia through microglia-mediated neuronal activation in the spinal dorsal horn.

The CCL2 elevation in primary afferent fibers produces zymosan-induced hyperalgesia through microglia-mediated neuronal activation in the spinal dorsal horn. Brain Res Bull. 2019 Apr 18;: Authors: Chun S, Bae Kwon Y Abstract Although C-C motif chemokine ligand 2 (CCL2) plays a critical role in the pathogenesis of neuropathic pain through neuron-microglia interactions, its pronociceptive function underlying inflammatory pain remains to be fully understood. The present study aimed to elucidate the potential role of CCL2 in pain sensitization following zymosan-induced inflammation. Intraplantar injection of zymosan into the rat hind paw significantly increased the expression of CCL2 in both dorsal root ganglions and the superficial dorsal horn. The expression of CCL2 was exclusively present in the isolectin B4-positive unmyelinated primary afferent fibers, but no in other cells of the spinal cord. Intrathecal administration of RS504393 (a CCR2 antagonist) markedly reduced the zymosan-induced thermal and mechanical hyperalgesia accompanied with reduced expression in the spinal cord of c-Fos, CD11b, phosphorylated p38 mitogen activated protein kinases (p-p38), and interleukin-1β. Whole cell patch-clamp recordings on spinal cord slices further revealed that the incubation of CCL2 evoked an evident inward current in substantia gelatinosa neurons and increased level of p-p38 in microglia. Moreover, co-incubation with minocycline (an inhibitor of microglial ...
Source: Brain Research Bulletin - Category: Neurology Authors: Tags: Brain Res Bull Source Type: research

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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
A 20-year-old man submitted to surgical insertion of a lumboperitoneal drain as a treatment for intracranial hypertension, secondary to venous sinus thrombosis, developed severe headache accompanied by nausea, vomiting, and diplopia 24 hours postoperative. Cerebral spinal fluid low-pressure headache was diagnosed. A transnasal sphenopalatine ganglion block with ropivacaine was performed without complications. Pain relief was immediate, complete, and sustained for about 24 hours; a second block was performed effectively with pain control, and the patient was discharged. Sphenopalatine ganglion block may be a safe and effici...
Source: A&A Case Reports - Category: Anesthesiology Tags: Case Reports Source Type: research
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