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Proceedings of the National Academy of... Apr 2023Fibromyalgia is a debilitating widespread chronic pain syndrome that occurs in 2 to 4% of the population. The prevailing view that fibromyalgia results from central...
Fibromyalgia is a debilitating widespread chronic pain syndrome that occurs in 2 to 4% of the population. The prevailing view that fibromyalgia results from central nervous system dysfunction has recently been challenged with data showing changes in peripheral nervous system activity. Using a mouse model of chronic widespread pain through hyperalgesic priming of muscle, we show that neutrophils invade sensory ganglia and confer mechanical hypersensitivity on recipient mice, while adoptive transfer of immunoglobulin, serum, lymphocytes, or monocytes has no effect on pain behavior. Neutrophil depletion abolishes the establishment of chronic widespread pain in mice. Neutrophils from patients with fibromyalgia also confer pain on mice. A link between neutrophil-derived mediators and peripheral nerve sensitization is already established. Our observations suggest approaches for targeting fibromyalgia pain via mechanisms that cause altered neutrophil activity and interactions with sensory neurons.
Topics: Humans; Chronic Pain; Fibromyalgia; Neutrophils; Hyperalgesia; Ganglia, Sensory
PubMed: 37071676
DOI: 10.1073/pnas.2211631120 -
Pain Medicine (Malden, Mass.) Jun 2019The dorsal root ganglion (DRG) is a novel target for neuromodulation, and DRG stimulation is proving to be a viable option in the treatment of chronic intractable... (Review)
Review
OBJECTIVE
The dorsal root ganglion (DRG) is a novel target for neuromodulation, and DRG stimulation is proving to be a viable option in the treatment of chronic intractable neuropathic pain. Although the overall principle of conventional spinal cord stimulation (SCS) and DRG stimulation-in which an electric field is applied to a neural target with the intent of affecting neural pathways to decrease pain perception-is similar, there are significant differences in the anatomy and physiology of the DRG that make it an ideal target for neuromodulation and may account for the superior outcomes observed in the treatment of certain chronic neuropathic pain states. This review highlights the anatomy of the DRG, its function in maintaining homeostasis and its role in neuropathic pain, and the unique value of DRG as a target in neuromodulation for pain.
METHODS
A narrative literature review was performed.
RESULTS
Overall, the DRG is a critical structure in sensory transduction and modulation, including pain transmission and the maintenance of persistent neuropathic pain states. Unique characteristics including selective somatic organization, specialized membrane characteristics, and accessible and consistent location make the DRG an ideal target for neuromodulation. Because DRG stimulation directly recruits the somata of primary sensory neurons and harnesses the filtering capacity of the pseudounipolar neural architecture, it is differentiated from SCS, peripheral nerve stimulation, and other neuromodulation options.
CONCLUSIONS
There are several advantages to targeting the DRG, including lower energy usage, more focused and posture-independent stimulation, reduced paresthesia, and improved clinical outcomes.
Topics: Chronic Pain; Electric Stimulation Therapy; Ganglia, Spinal; Humans; Neuralgia
PubMed: 31152179
DOI: 10.1093/pm/pnz012 -
Journal of Visualized Experiments : JoVE Oct 2018Dorsal root ganglia (DRG) contain cell bodies of sensory neurons. This type of neuron is pseudo-unipolar, with two axons that innervate peripheral tissues, such as skin,...
Dorsal root ganglia (DRG) contain cell bodies of sensory neurons. This type of neuron is pseudo-unipolar, with two axons that innervate peripheral tissues, such as skin, muscle and visceral organs, as well as the spinal dorsal horn of the central nervous system. Sensory neurons transmit somatic sensation, including touch, pain, thermal, and proprioceptive sensations. Therefore, DRG primary cultures are widely used to study the cellular mechanisms of nociception, physiological functions of sensory neurons, and neural development. The cultured neurons can be applied in studies involving electrophysiology, signal transduction, neurotransmitter release, or calcium imaging. With DRG primary cultures, scientists may culture dissociated DRG neurons to monitor biochemical changes in single or multiple cells, overcoming many of the limitations associated with in vivo experiments. Compared to commercially available DRG-hybridoma cell lines or immortalized DRG neuronal cell lines, the composition and properties of the primary cells are much more similar to sensory neurons in tissue. However, due to the limited number of cultured DRG primary cells that can be isolated from a single animal, it is difficult to perform high-throughput screens for drug targeting studies. In the current article, procedures for DRG collection and culture are described. In addition, we demonstrate the treatment of cultured DRG cells with an agonist of neuropeptide FF receptor type 2 (NPFFR2) to induce the release of peptide neurotransmitters (calcitonin gene-related peptide (CRGP) and substance P (SP)).
Topics: Animals; Calcitonin Gene-Related Peptide; Cells, Cultured; Ganglia, Spinal; Neurogenesis; Neuropeptides; Rats; Receptors, Neuropeptide; Sensory Receptor Cells; Substance P; Synaptic Transmission
PubMed: 30346383
DOI: 10.3791/57569 -
The Journal of Neuroscience : the... Nov 2009Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of...
Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.
Topics: Acoustic Stimulation; Animals; Cell Death; Cochlear Nerve; Ear, Inner; Ganglia, Sensory; Hearing Loss, Noise-Induced; Male; Mice; Mice, Inbred CBA; Nerve Degeneration; Neurons; Neurons, Afferent; Noise; Otoacoustic Emissions, Spontaneous; Synapses; Vestibulocochlear Nerve Diseases
PubMed: 19906956
DOI: 10.1523/JNEUROSCI.2845-09.2009 -
STAR Protocols Mar 2021In this protocol, we provide step-by-step instructions for dissection and culture of primary murine dorsal root ganglia (DRG), which provide an opportunity to study the...
In this protocol, we provide step-by-step instructions for dissection and culture of primary murine dorsal root ganglia (DRG), which provide an opportunity to study the functional properties of peripheral sensory neurons . Further, we describe the analysis of neuropeptide release by ELISA as a possible downstream application. In addition, isolated DRGs can be used directly for immunofluorescence, flow cytometry, RNA sequencing or proteomic approaches, electrophysiology, and calcium imaging. For complete details on the use and execution of this protocol, please refer to Perner et al. (2020).
Topics: Animals; Ganglia, Spinal; Mice; Neuropeptides; Proteomics; Sensory Receptor Cells; Tissue Culture Techniques
PubMed: 33615276
DOI: 10.1016/j.xpro.2021.100333 -
Current Problems in Dermatology 2016A multitude of exogenous environmental stimuli and endogenous molecular and cellular components interface directly or indirectly with the free nerve endings of sensory... (Review)
Review
A multitude of exogenous environmental stimuli and endogenous molecular and cellular components interface directly or indirectly with the free nerve endings of sensory nerves in the skin. Environmental stimuli include substances derived from the microbiome and materials, such as allergens, that otherwise come in contact with the skin. Endogenous stimuli include components of or mediators derived from the epidermal barrier, keratinocytes, mast cells, and additional resident and skin-homing immune cells. The sensation of itch is ultimately provoked by mediators that interact with and activate pruriceptors on the sensory nerve fibers. These peripheral fibers convey signals from the skin to the dorsal root and trigeminal ganglia and on to the spinal cord and brain where central processing of the itch sensation occurs. A discussion of the nature and sources of itch stimuli and receptors in the periphery form the basis of this chapter. The development of drugs that target these processes is in the process of revolutionizing therapeutic approaches to itch.
Topics: Acute Disease; Allergens; Brain; Chronic Disease; Ganglia, Spinal; Humans; Keratinocytes; Mast Cells; Peripheral Nervous System; Pruritus; Sensory Receptor Cells; Skin; Spinal Cord; Trigeminal Ganglion
PubMed: 27578066
DOI: 10.1159/000446012 -
Cell Reports Feb 2022Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies....
Satellite glia are the major glial type found in sympathetic and sensory ganglia in the peripheral nervous system, and specifically, contact neuronal cell bodies. Sympathetic and sensory neurons differ in morphological, molecular, and electrophysiological properties. However, the molecular diversity of the associated satellite glial cells remains unclear. Here, using single-cell RNA sequencing analysis, we identify five different populations of satellite glia from sympathetic and sensory ganglia. We define three shared populations of satellite glia enriched in immune-response genes, immediate-early genes, and ion channels/ECM-interactors, respectively. Sensory- and sympathetic-specific satellite glia are differentially enriched for modulators of lipid synthesis and metabolism. Sensory glia are also specifically enriched for genes involved in glutamate turnover. Furthermore, satellite glia and Schwann cells can be distinguished by unique transcriptional signatures. This study reveals the remarkable heterogeneity of satellite glia in the peripheral nervous system.
Topics: Animals; Ganglia, Sensory; Ganglia, Spinal; Ganglia, Sympathetic; Humans; Mice; Neuroglia; Neurons; Neurons, Afferent; Peripheral Nervous System; Schwann Cells
PubMed: 35108545
DOI: 10.1016/j.celrep.2022.110328 -
Nature Reviews. Neuroscience Sep 2020Satellite glial cells (SGCs) closely envelop cell bodies of neurons in sensory, sympathetic and parasympathetic ganglia. This unique organization is not found elsewhere... (Review)
Review
Satellite glial cells (SGCs) closely envelop cell bodies of neurons in sensory, sympathetic and parasympathetic ganglia. This unique organization is not found elsewhere in the nervous system. SGCs in sensory ganglia are activated by numerous types of nerve injury and inflammation. The activation includes upregulation of glial fibrillary acidic protein, stronger gap junction-mediated SGC-SGC and neuron-SGC coupling, increased sensitivity to ATP, downregulation of Kir4.1 potassium channels and increased cytokine synthesis and release. There is evidence that these changes in SGCs contribute to chronic pain by augmenting neuronal activity and that these changes are consistent in various rodent pain models and likely also in human pain. Therefore, understanding these changes and the resulting abnormal interactions of SGCs with sensory neurons could provide a mechanistic approach that might be exploited therapeutically in alleviation and prevention of pain. We describe how SGCs are altered in rodent models of four common types of pain: systemic inflammation (sickness behaviour), post-surgical pain, diabetic neuropathic pain and post-herpetic pain.
Topics: Animals; Chronic Pain; Ganglia, Autonomic; Ganglia, Sensory; Humans; Satellite Cells, Perineuronal
PubMed: 32699292
DOI: 10.1038/s41583-020-0333-z -
Advances in Biological Regulation May 2016Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary... (Review)
Review
Somatosensory neurons of the dorsal root ganglia (DRG) and trigeminal ganglia (TG) are responsible for detecting thermal and tactile stimuli. They are also the primary neurons mediating pain and itch. A large number of cell surface receptors in these neurons couple to phospholipase C (PLC) enzymes leading to the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and the generation of downstream signaling molecules. These neurons also express many different ion channels, several of which are regulated by phosphoinositides. This review will summarize the knowledge on phosphoinositide signaling in DRG neurons, with special focus on effects on sensory and other ion channels.
Topics: Animals; Calcium; Ganglia, Spinal; Gene Expression Regulation; Humans; Ion Channels; Isoenzymes; Neurons; Pain Perception; Phosphatidylinositol 4,5-Diphosphate; Sensory Thresholds; Signal Transduction; Touch Perception; Trigeminal Ganglion; Type C Phospholipases
PubMed: 26724974
DOI: 10.1016/j.jbior.2015.11.012 -
Journal of Anatomy Nov 2022Primary sensory neurons are a heterogeneous population of cells able to respond to both innocuous and noxious stimuli. Like most neurons they are highly... (Review)
Review
Primary sensory neurons are a heterogeneous population of cells able to respond to both innocuous and noxious stimuli. Like most neurons they are highly compartmentalised, allowing them to detect, convey and transfer sensory information. These compartments include specialised sensory endings in the skin, the nodes of Ranvier in myelinated axons, the cell soma and their central terminals in the spinal cord. In this review, we will highlight the importance of these compartments to primary afferent function, describe how these structures are compromised following nerve damage and how this relates to neuropathic pain.
Topics: Axons; Ganglia, Spinal; Neurons; Neurons, Afferent; Spinal Cord
PubMed: 34528255
DOI: 10.1111/joa.13544