A New “Kine” of Pain: MCP-1 and Sensory Neuron Excitability. Focus on “MCP-1 Enhances Excitability of Nociceptive Neurons in Chronically Compressed Dorsal Root Ganglia”

2006 ◽  
Vol 96 (5) ◽  
pp. 2171-2172 ◽  
Author(s):  
Cynthia M. Hingtgen
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Nociceptive Neurons ◽  
Neuron Excitability

M2-Receptor Subtype Does Not Mediate Muscarine-Induced Increases in [Ca2+]i in Nociceptive Neurons of Rat Dorsal Root Ganglia

2000 ◽  
Vol 84 (4) ◽  
pp. 1934-1941 ◽  
Author(s):  
Rainer Haberberger ◽  
Reas Scholz ◽  
Wolfgang Kummer ◽  
Michaela Kress
Keyword(s):  
Receptor Antagonist ◽  
Muscarinic Receptor ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Muscarinic Receptor Subtypes ◽  
Rt Pcr ◽  
Nociceptive Neurons

Multiple muscarinic receptor subtypes are present on sensory neurons that may be involved in the modulation of nociception. In this study we focused on the presence of the muscarinic receptor subtypes, M2 and M3 (M2R, M3R), in adult rat lumbar dorsal root ganglia (DRG) at the functional ([Ca2+]i measurement), transcriptional (RT-PCR), and translational level (immunohistochemistry). After 1 day in culture exposure of dissociated medium-sized neurons (20–35 μm diam) to muscarine was followed by rises in [Ca2+]i in 76% of the neurons. The [Ca2+]i increase was absent after removal of extracellular calcium and did not desensitize after repetitive application of the agonist. This rise in [Ca2+]i may be explained by the expression of M3R, which can induce release of calcium from internal stores via inositoltrisphospate. Indeed the effect was antagonized by the muscarinic receptor antagonist atropine as well as by the M3R antagonist, 4-diphenylacetoxy-N-(2 chloroethyl)-piperidine hydrochloride (4-DAMP). The pharmacological identification of M3R was corroborated by RT-PCR of total RNA and single-cell RT-PCR, which revealed the presence of mRNA for M3R in lumbar DRG and in single sensory neurons. In addition, RT-PCR also revealed the expression of M2R, which did not seem to contribute to the calcium changes since it was not prevented by the M2 receptor antagonist, gallamine. Immunohistochemistry demonstrated the presence of M2R and M3R in medium-sized lumbar DRG neurons that also coexpressed binding sites for the lectin I-B4, a marker for mainly cutaneous nociceptors. The occurrence of muscarinic receptors in putative nociceptive I-B4-positive neurons suggests the involvement of these acetylcholine receptors in the modulation of processing of nociceptive stimuli.

scholarly journals Enhanced T-type calcium channel 3.2 activity in sensory neurons contributes to neuropathic-like pain of monosodium iodoacetate-induced knee osteoarthritis

2020 ◽  
Vol 16 ◽  
pp. 174480692096380
Author(s):  
Seung Min Shin ◽  
Yongsong Cai ◽  
Brandon Itson-Zoske ◽  
Chensheng Qiu ◽  
Xu Hao ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Spinal Dorsal Horn ◽  
Primary Sensory Neurons ◽  
Primary Sensory Neuron ◽  
Spinal Dorsal ◽  
Osteoarthritis Pain ◽  
Monosodium Iodoacetate

The monosodium iodoacetate knee osteoarthritis model has been widely used for the evaluation of osteoarthritis pain, but the pathogenesis of associated chronic pain is not fully understood. The T-type calcium channel 3.2 (CaV3.2) is abundantly expressed in the primary sensory neurons, in which it regulates neuronal excitability at both the somata and peripheral terminals and facilitates spontaneous neurotransmitter release at the spinal terminals. In this study, we investigated the involvement of primary sensory neuron-CaV3.2 activation in monosodium iodoacetate osteoarthritis pain. Knee joint osteoarthritis pain was induced by intra-articular injection of monosodium iodoacetate (2 mg) in rats, and sensory behavior was evaluated for 35 days. At that time, knee joint structural histology, primary sensory neuron injury, and inflammatory gliosis in lumbar dorsal root ganglia, and spinal dorsal horn were examined. Primary sensory neuron-T-type calcium channel current by patch-clamp recording and CaV3.2 expression by immunohistochemistry and immunoblots were determined. In a subset of animals, pain relief by CaV3.2 inhibition after delivery of CaV3.2 inhibitor TTA-P2 into sciatic nerve was investigated. Knee injection of monosodium iodoacetate resulted in osteoarthritis histopathology, weight-bearing asymmetry, sensory hypersensitivity of the ipsilateral hindpaw, and inflammatory gliosis in the ipsilateral dorsal root ganglia, sciatic nerve, and spinal dorsal horn. Neuronal injury marker ATF-3 was extensively upregulated in primary sensory neurons, suggesting that neuronal damage was beyond merely knee-innervating primary sensory neurons. T-type current in dissociated primary sensory neurons from lumbar dorsal root ganglia of monosodium iodoacetate rats was significantly increased, and CaV3.2 protein levels in the dorsal root ganglia and spinal dorsal horn ipsilateral to monosodium iodoacetate by immunoblots were significantly increased, compared to controls. Perineural application of TTA-P2 into the ipsilateral sciatic nerve alleviated mechanical hypersensitivity and weight-bearing asymmetry in monosodium iodoacetate osteoarthritis rats. Overall, our findings demonstrate an elevated CaV3.2 expression and enhanced function of primary sensory neuron-T channels in the monosodium iodoacetate osteoarthritis pain. Further study is needed to delineate the importance of dysfunctional primary sensory neuron-CaV3.2 in osteoarthritis pain.

Cyclooxygenase-1 is a marker for a subpopulation of putative nociceptive neurons in rat dorsal root ganglia

2000 ◽  
Vol 12 (3) ◽  
pp. 911-920 ◽  
Author(s):  
B. Chopra ◽  
S. Giblett ◽  
J. G. Little ◽  
L. F. Donaldson ◽  
S. Tate ◽  
...  
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Nociceptive Neurons ◽  
Cyclooxygenase 1

Role of myosin Va in neuritogenesis of chick dorsal root ganglia nociceptive neurons

2013 ◽  
Vol 38 (3) ◽  
pp. 388-394 ◽  
Author(s):  
Tatiane Y. N. Kanno ◽  
Enilza M. Espreafico ◽  
Chao Yun Irene Yan
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Nociceptive Neurons ◽  
Myosin Va

scholarly journals Identification of genes regulating sensory neuron genesis and differentiation in the avian dorsal root ganglia

2004 ◽  
Vol 229 (3) ◽  
pp. 618-629 ◽  
Author(s):  
Branden R. Nelson ◽  
Meru Sadhu ◽  
Jennifer C. Kasemeier ◽  
Lawrence W. Anderson ◽  
Frances Lefcort
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root

Conditional gene deletion in primary nociceptive neurons of trigeminal ganglia and dorsal root ganglia

genesis ◽  
2004 ◽  
Vol 38 (3) ◽  
pp. 122-129 ◽  
Author(s):  
Nitin Agarwal ◽  
Stefan Offermanns ◽  
Rohini Kuner
Keyword(s):  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Gene Deletion ◽  
Trigeminal Ganglia ◽  
Nociceptive Neurons

scholarly journals Cannabinoid Receptor 1 Expression in Human Dorsal Root Ganglia and CB13-Induced Bidirectional Modulation of Sensory Neuron Activity

2021 ◽  
Vol 2 ◽  
Author(s):  
Zachary K. Ford ◽  
Ashlie N. Reker ◽  
Sisi Chen ◽  
Feni Kadakia ◽  
Alexander Bunk ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Sensory Neurons ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Cannabinoid Receptors ◽  
Calcium Influx ◽  
Membrane Properties ◽  
Neuron Activity ◽  
Membrane Excitability ◽  
Bidirectional Modulation

Cannabinoid receptors have been identified as potential targets for analgesia from studies on animal physiology and behavior, and from human clinical trials. Here, we sought to improve translational understanding of the mechanisms of cannabinoid-mediated peripheral analgesia. Human lumbar dorsal root ganglia were rapidly recovered from organ donors to perform physiological and anatomical investigations into the potential for cannabinoids to mediate analgesia at the level of the peripheral nervous system. Anatomical characterization of in situ gene expression and immunoreactivity showed that 61 and 53% of human sensory neurons express the CB1 gene and receptor, respectively. Calcium influx evoked by the algogen capsaicin was measured by Fura-2AM in dissociated human sensory neurons pre-exposed to the inflammatory mediator prostaglandin E2 (PGE2) alone or together with CB13 (1 μM), a cannabinoid agonist with limited blood–brain barrier permeability. Both a higher proportion of neurons and a greater magnitude of response to capsaicin were observed after exposure to CB13, indicating cannabinoid-mediated sensitization. In contrast, membrane properties measured by patch-clamp electrophysiology demonstrated that CB13 suppressed excitability and reduced action potential discharge in PGE2-pre-incubated sensory neurons, suggesting the suppression of sensitization. This bidirectional modulation of sensory neuron activity suggests that cannabinoids may suppress overall membrane excitability while simultaneously enhancing responsivity to TRPV1-mediated stimuli. We conclude that peripherally restricted cannabinoids may have both pro- and anti-nociceptive effects in human sensory neurons.

scholarly journals Expression of huntingtin-associated protein 1 in adult mouse dorsal root ganglia and its neurochemical characterization in reference to sensory neuron subpopulations

IBRO Reports ◽  
2020 ◽  
Vol 9 ◽  
pp. 258-269 ◽  
Author(s):  
Md Nabiul Islam ◽  
Naoki Maeda ◽  
Emi Miyasato ◽  
Mir Rubayet Jahan ◽  
Abu Md Mamun Tarif ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Adult Mouse

scholarly journals Sensitization of Cutaneous Primary Afferents in Bone Cancer Revealed by In Vivo Calcium Imaging

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3491
Author(s):  
Larissa de Clauser ◽  
Ana P. Luiz ◽  
Sonia Santana-Varela ◽  
John N. Wood ◽  
Shafaq Sikandar
Keyword(s):  
Bone Marrow ◽  
Dorsal Root Ganglia ◽  
Calcium Imaging ◽  
Dorsal Root ◽  
Primary Afferents ◽  
Cutaneous Afferents ◽  
Retrograde Labelling ◽  
Nociceptive Neurons ◽  
In Vivo Calcium Imaging

Cancer-induced bone pain (CIBP) is a complex condition, comprising components of inflammatory and neuropathic processes, but changes in the physiological response profiles of bone-innervating and cutaneous afferents remain poorly understood. We used a combination of retrograde labelling and in vivo calcium imaging of bone marrow-innervating dorsal root ganglia (DRG) neurons to determine the contribution of these cells in the maintenance of CIBP. We found a majority of femoral bone afferent cell bodies in L3 dorsal root ganglia (DRG) that also express the sodium channel subtype Nav1.8—a marker of nociceptive neurons—and lack expression of parvalbumin—a marker for proprioceptive primary afferents. Surprisingly, the response properties of bone marrow afferents to both increased intraosseous pressure and acid were unchanged by the presence of cancer. On the other hand, we found increased excitability and polymodality of cutaneous afferents innervating the ipsilateral paw in cancer bearing animals, as well as a behavioural phenotype that suggests changes at the level of the DRG contribute to secondary hypersensitivity. This study demonstrates that cutaneous afferents at distant sites from the tumour bearing tissue contribute to mechanical hypersensitivity, highlighting these cells as targets for analgesia.

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