Functional imaging in microfluidic chambers reveals sensory neuron sensitivity is differentially regulated between neuronal regions

Primary afferent sensory neurons are incredibly long cells, often traversing distances of over 1 m in humans. Cutaneous sensory stimuli are transduced in the periphery by specialised end organs or free nerve endings, which code the stimulus into electrical action potentials that propagate towards the central nervous system. Despite significant advances in our knowledge of sensory neuron physiology and ion channel expression, many commonly used techniques fail to accurately model the primary afferent neuron in its entirety. In vitro experiments often focus on the cell somata and neglect the fundamental processes of peripheral stimulus transduction and action potential propagation. Despite this, these experiments are commonly used as a model for cellular investigations of the receptive terminals. We demonstrate that ratiometric calcium imaging performed in compartmentalised sensory neuron cultures can be used to directly and accurately compare the sensitivity and functional protein expression of isolated neuronal regions in vitro. Using microfluidic chambers, we demonstrate that the nerve terminals of cultured dorsal root ganglion neurons can be depolarised to induce action potential propagation, which has both tetrodotoxin-resistant and tetrodotoxin-sensitive components. Furthermore, we show that there is a differential regulation of proton sensitivity between the sensory terminals and somata in cultured sensory neurons. We also demonstrate that capsaicin sensitivity is highly...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research

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ConclusionsOur findings suggest that spinal and trigeminal neuropathies due to trauma are differentially regulated. Subtle but important differences between the two ganglia may affect NP development.
Source: European Journal of Pain - Category: Anesthesiology Authors: Tags: ORIGINAL ARTICLE Source Type: research
Conclusion: miR-384-5p is a negative regulator in the development of neuropathic pain by regulating SCN3A, indicating that miR-384-5p might be a promising therapeutic target in the treatment of neuropathic pain.Abbreviations: CCI: Chronic constriction injury; ZEB1: Zinc finger E box binding protein-1; MAPK6: Mitogen-activated protein kinase 6; COX-2: cyclooxygenase-2. PMID: 32098588 [PubMed - as supplied by publisher]
Source: Neurological Research - Category: Neurology Tags: Neurol Res Source Type: research
ConclusionThis is the first ever study reporting the changes in cerebral metabolic activity and multi ‐frame static brain18F FDG PET imaging after L2 DRG stimulation for discogenic low back pain. Predominantly an increased metabolic activity in nociceptive brain matrices are seen with an increased in F18F FDG uptake following L2 DRG stimulation.
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Clinical Research Source Type: research
Authors: Jia Q, Dong W, Zhang L, Yang X Abstract Neuropathic pain is clinically unsatisfactorily treated because of unclear mechanisms. The present study aims to explore the concrete mechanisms underlying the alleviation of resveratrol-activated silent information regulator 1 (Sirt1) to chronic constriction injury (CCI)-induced neuropathic pain. CCI surgery was conducted to the unilateral sciatic nerve of male Sprague-Dawley rats to induce neuropathic pain experimentally. Resveratrol with or without miR-182 antagomir were administered to CCI rats via intrathecal catheter. Behavioral tests including paw withdrawal t...
Source: Channels - Category: Molecular Biology Tags: Channels (Austin) Source Type: research
Source: Journal of Pain Research - Category: Anesthesiology Tags: Journal of Pain Research Source Type: research
ConclusionsChronic hand pain is a prevalent and serious condition and can cause significant morbidity and disability and interferes with independence and activities of daily living. Conservative treatment remains the first line of treatment; however, when first-line treatments fail, steroid injections can usually provide benefit. In some cases, HA or Botox may also be beneficial. US-guidance is increasing in hand injection and almost ubiquitously provides safer, more effective injections. Hand surgery remains the alternative for refractory pain.
Source: Pain and Therapy - Category: Anesthesiology Source Type: research
In this study, olfactory ensheathing cells (OECs) were cultured, chitosan (CS) was prepared, and the compatibility of CS and OECs was detected by MTT method. Animal model of chronic constrictive sciatic nerve injury (CCI) was made, OECs and OECs+CS were transplanted to the region surrounding the chronic sciatic nerve injury, and the difference between the two groups in the treatment of NPP was compared. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured by using behavioral method. In situ hybridization and Western-blotting were used to detect the expression of P2X4R mRNA and protei...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research
CONCLUSIONS: Preoperative SPGB is an effective option to reduce POP and the need for rescue analgesics for patients undergoing SRP. CLINICAL TRIAL NUMBER: NCT04020393. PMID: 32090594 [PubMed - as supplied by publisher]
Source: The Annals of Otology, Rhinology, and Laryngology - Category: ENT & OMF Authors: Tags: Ann Otol Rhinol Laryngol Source Type: research
Preventing and treating opioid dependence and withdrawal is a major clinical challenge, and the underlying mechanisms of opioid dependence and withdrawal remain elusive. We hypothesized that prolonged morphine exposure or chronic inflammation-induced μ-opioid receptor activity serves as a severe stress that elicits neuronal alterations and recapitulates events during development. Here, we report that Wnt signaling, which is important in developmental processes of the nervous system, plays a critical role in withdrawal symptoms from opioid receptor activation in mice. Repeated exposures of morphine or peripheral inflamma...
Source: Pain - Category: Anesthesiology Tags: Research Paper Source Type: research
Emerging immunotherapies with monoclonal antibodies against programmed cell death protein–1 (PD-1) have shown success in treating cancers. However, PD-1 signaling in neurons is largely unknown. We recently reported that dorsal root ganglion (DRG) primary sensory neurons express PD-1 and activation of PD-1 inhibits neuronal excitability and pain. Opioids are mainstay treatments for cancer pain, and morphine produces antinociception via mu opioid receptor (MOR). Here, we report that morphine antinociception and MOR signaling require neuronal PD-1. Morphine-induced antinociception after systemic or intrathecal injection...
Source: Science Translational Medicine - Category: Biomedical Science Authors: Tags: Research Articles Source Type: research
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