Hyperpolarization-activated cyclic nucleotide–gated channels contribute to spontaneous activity in L4 C-fiber nociceptors, but not Aβ-non-nociceptors, after axotomy of L5-spinal nerve in the rat in vivo

Peripheral neuropathic pain associated with partial nerve injury is believed to be driven partly by aberrant spontaneous activity (SA) in both injured and uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are not fully understood, but hyperpolarization-activated cyclic nucleotide–gated (HCN) channels which underlie the excitatory Ih current have been implicated in SA generation in axotomized A-fiber neurons after L5-spinal nerve ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with neuroinflammation-inducing chromic gut, we examined whether HCN channels also contribute to SA in the adjacent L4-neurons. Intracellular recordings from L4-DRG neurons in control rats, and L4-DRG neurons in mSNA rats were made using in vivo voltage- and current-clamp techniques. Compared with control, L4 C-nociceptors and Aβ-low-threshold mechanoreceptors (LTMs) exhibited SA 7 days after mSNA. This was accompanied, in C-nociceptors, by a significant increase in Ih amplitude, the percentage of Ih-expressing neurons, and Ih activation rate. Hyperpolarization-activated cyclic nucleotide–gated channel blockade with ZD7288 (10 mg/kg, intravenously) suppressed SA in C-nociceptors, but not Aβ-LTMs, and caused in C-nociceptors, membrane hyperpolarization and a decrease in Ih activation rate. Furthermore, intraplantar injection of ZD7288 (100 μM) was found t...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

Related Links:

ConclusionsDRG stimulation is an effective and safe therapy for various etiologies of chronic pain.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Clinical Research Source Type: research
ConclusionA case of SNF with classic NF1 mutation in a classic NF1 family was identified for the first time, indicating that SNF may share the same gene mutation with NF1, while the different manifestation of NF1 and SNF may be related to gene modification.
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: CLINICAL REPORT Source Type: research
Authors: Chaudhary B, Tripathy PR, Gaikwad MR Abstract Vertebral artery is a branch of 1st part of subclavian artery. Vertebral artery arising from the aortic arch most commonly presents on the left side. The cervical part of sympathetic trunk is closely related to the vertebral artery in the cervical region. Though lots of variations regarding anomalous origin, course of vertebral artery is reported in the literature, here we present a rare anomaly in which vertebral artery after originating from aortic arch is passing through stellate ganglia and it enters into the transverse foramina of higher cervical vertebra ...
Source: Folia Morphologica - Category: Anatomy Tags: Folia Morphol (Warsz) Source Type: research
ConclusionsThere is limited evidence for the appropriate treatment alternatives, but from data currently available the conversion from conventional tonic stimulation to burst, high frequency (10  kHz), multiple wave forms, and/or DRGs may be appropriate in select patients and will require further research to determine the most appropriate first line salvage in the context of the underlying pain pathology.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Review Article Source Type: research
CONCLUSION: The current data suggested that inhibitory changes in proteins from the apoptotic pathway in anti-SSTR2-treated groups might be taking place to overcome the protein deficits caused by SSTR2 antibody and supported the new therapeutic intervention with SSTR2 antagonist for neuronal degeneration following nerve injury. PMID: 31686636 [PubMed - as supplied by publisher]
Source: CNS and Neurological Disorders Drug Targets - Category: Drugs & Pharmacology Authors: Tags: CNS Neurol Disord Drug Targets Source Type: research
CONCLUSION: We have demonstrated that OMC exhibits advanced analgesic, antipruritic and anti-inflammatory effects when compared with OG and OMP in ACD mice by regulating inflammation, chemokines, immune mediators and inhibiting the mRNA expression of TRPA1 and TRPV1. OMC has no irritation to the intact and damaged skin of rabbits. PMID: 31654757 [PubMed - as supplied by publisher]
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharm Sci Source Type: research
AbstractIntroductionVarious drugs are used to treat patients with neuropathic pain; however, optimal treatment using acetaminophen (A) and/or tramadol (T) remains unclear. The evidence supporting the drug choice and the timing of administration is insufficient. Therefore, the objective of the present study was to investigate the effect of T and/or A on pain-related behavior in a nucleus pulposus (NP) rat model.Materials and methodsSprague –Dawley rats (n = 180) were divided into NP-A (52 mg/kg), NP-T (6 mg/kg), NP-AT (combined A and T), NP-S (saline), and sham groups (n = 36 per ...
Source: European Spine Journal - Category: Orthopaedics Source Type: research
ConclusionsT12 DRG ‐S can be an effective treatment for chronic axial low back pain. Stimulation results in reduced pain and disability, while improving quality of life. These outcomes can be achieved without paresthesias.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Case Series Source Type: research
Publication date: Available online 3 October 2019Source: Neurochemistry InternationalAuthor(s): Jiu Lin, Yan-yan Zhang, Fei Liu, Xin-yi Fang, Meng-ke Liu, Chao-lan Huang, Hang Wang, Da-qing Liao, Cheng Zhou, Jie-fei ShenAbstractP2Y purinergic receptors expressed in neurons and satellite glial cells (SGCs) of the trigeminal ganglion (TG) contributes to inflammatory and neuropathic pain. P2Y14 receptor expression is reported in the spinal cord, dorsal root ganglion (DRG), and TG. In present study, the role of P2Y14 receptor in the TG in inflammatory orofacial pain of Sprague-Dawley (SD) rats was investigated. Peripheral inje...
Source: Neurochemistry International - Category: Neuroscience Source Type: research
In this study, we used the hot-plate and Von Frey tests to evaluate the thermal and mechanical hyperalgesia. Protein expressions of TRPV1 and protein kinase C (PKC) in dorsal root ganglion were assayed by western blotting and mRNA level of Trpv1, Trpa1, Trpv4, and Trpm8 were assayed by real-time PCR. TNF-α, IL-1β, and IL-6 levels in spinal cord were measured by ELISA. Immunofluorescence assay was applied to analyze the activation of astrocyte in spinal cord. Continuing infusion of remifentanil induced thermal hyperalgesia and mechanical allodynia, which were accompanied by upregulation of TRPV1 and PKC protein i...
Source: NeuroReport - Category: Neurology Tags: Cellular, Molecular and Developmental Neuroscience Source Type: research
More News: Anesthesiology | Back Pain | Brain | Gabapentin | Ganglions | Neurology | Neurontin | Pain