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PloS One 2011Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and...
Scratching relieves itch, but the underlying neural mechanisms are poorly understood. We presently investigated a role for the inhibitory neurotransmitters GABA and glycine in scratch-evoked inhibition of spinal itch-signaling neurons in a mouse model of chronic dry skin itch. Superficial dorsal horn neurons ipsilateral to hindpaw dry skin treatment exhibited a high level of spontaneous firing that was significantly attenuated by cutaneous scratching, pinch and noxious heat. Scratch-evoked inhibition was nearly abolished by spinal delivery of the glycine antagonist, strychnine, and was markedly attenuated by respective GABA(A) and GABA(B) antagonists bicuculline and saclofen. Scratch-evoked inhibition was also significantly attenuated (but not abolished) by interruption of the upper cervical spinal cord, indicating the involvement of both segmental and suprasegmental circuits that engage glycine- and GABA-mediated inhibition of spinal itch-signaling neurons by noxious counterstimuli.
Topics: Action Potentials; Animals; Cervical Vertebrae; GABA Antagonists; Glycine; Mice; Mice, Inbred ICR; Models, Neurological; Nerve Block; Neural Inhibition; Neural Pathways; Neurons; Neurotransmitter Agents; Physical Stimulation; Pruritus; Signal Transduction; Spinal Nerves; Strychnine; Temperature
PubMed: 21818363
DOI: 10.1371/journal.pone.0022665 -
Anesthesiology Jun 2003Intrathecal adenosine is antinociceptive under conditions of central sensitization, but not in response to acute stimuli in normals. The reasons for this selective...
BACKGROUND
Intrathecal adenosine is antinociceptive under conditions of central sensitization, but not in response to acute stimuli in normals. The reasons for this selective circumstance of action remain unclear, but some evidence links adenosine's antinociceptive effects to release of norepinephrine by terminals in the spinal cord. The purpose of this study was to test whether spinal adenosine induces norepinephrine release selectively in settings of hypersensitivity.
METHODS
Rats randomly assigned to spinal nerve ligation, sham operation, or no operation were anesthetized. A microdialysis fiber was implanted in the spinal cord dorsal horn at the L5-L6 level and perfused with artificial cerebrospinal fluid. After washout and a baseline sample period, adenosine at various concentrations was infused through the fiber for 150 min, and samples were collected every 15 min.
RESULTS
In ligated, but not in sham or normal animals, adenosine perfusion increased norepinephrine in spinal cord microdialysates in a concentration-dependent manner. The effects of adenosine plateaued after 75 min and remained stable until the end of the experiment. Intravenous injection of selective adenosine A1 and A2 receptor antagonists revealed that adenosine's effect on spinal norepinephrine release was A1 receptor mediated.
CONCLUSIONS
This is the first study to provide direct evidence that adenosine is able to release norepinephrine in spinal cord dorsal horns in living animals. However, this effect was only seen in animals after spinal nerve ligation. These data are consistent with behavioral studies demonstrating that adenosine's antinociceptive effects in rats after spinal nerve ligation is totally dependent on intact spinal noradrenergic terminals and can be blocked by spinal alpha 2-adrenergic receptor antagonists.
Topics: Adenosine; Animals; Dose-Response Relationship, Drug; Injections, Spinal; Ligation; Male; Microdialysis; Norepinephrine; Rats; Rats, Sprague-Dawley; Spinal Cord; Spinal Nerves; Theobromine; Time Factors; Xanthines
PubMed: 12766658
DOI: 10.1097/00000542-200306000-00024 -
AJNR. American Journal of Neuroradiology Feb 1995To examine histopathologically the endothelium of contrast-enhancing spinal nerve roots.
PURPOSE
To examine histopathologically the endothelium of contrast-enhancing spinal nerve roots.
METHODS
In five adult baboons, chronic compression of the left S-1 spinal nerve root sufficient to produce a change in the evoked potential was produced by means of a suture tied around the nerve. The animals were studied with MR at 8 and 16 days after nerve compression and then killed for histopathologic and electron microscopic studies. Histopathologic changes in the nerve roots demonstrating contrast enhancement were described.
RESULTS
In all compressed spinal nerves, contrast enhancement was observed. Histopathologically, wallerian degeneration of the root and inflammation and disruption of the endothelium of capillaries in the spinal nerve were evident.
CONCLUSIONS
Degenerative changes in the nerve root and the capillary endothelium of a lumbar spinal nerve are associated with contrast enhancement.
Topics: Animals; Magnetic Resonance Imaging; Papio; Spinal Nerve Roots; Ultrasonography
PubMed: 7726071
DOI: No ID Found -
Molecular Pain 2019Electroacupuncture has been shown to effectively reduce chronic pain in patients with nerve injury. The underlying mechanisms are not well understood. Accumulated...
Electroacupuncture has been shown to effectively reduce chronic pain in patients with nerve injury. The underlying mechanisms are not well understood. Accumulated evidence suggests that purinergic P2X3 receptors (P2X3Rs) in dorsal root ganglion neurons play a major role in mediating chronic pain associated with nerve injury. The aim of this study is to determine if electroacupuncture stimulation alters P2X3R activity in dorsal root ganglia to produce analgesia under neuropathic pain condition. Peripheral neuropathy was produced by ligation of the left lumbar 5 (L5) spinal nerve in rats. Low-frequency (2 Hz) electrical stimulation was applied to ipsilateral ST36 and BL60 acupoints in rats. The P2X3R agonist (α,β-meATP)-induced flinch responses were reduced after electroacupuncture treatment. Western analyses showed that P2X3R expression was upregulated in nerve-uninjured lumbar 4 (L4) dorsal root ganglion neurons ipsilateral to the spinal nerve ligation. Electroacupuncture-stimulation reversed the upregulation. In nerve-injured L5 dorsal root ganglia, P2X3R expression was substantially reduced. Electroacupuncture had no effect on the reduction. We also determined the injury state of P2X3R expressing dorsal root ganglion neurons using the neuronal injury marker, activating transcription factor 3 (ATF3). Immunohistochemical assay showed that in L4 dorsal root ganglia, almost all P2X3Rs were expressed in uninjured (ATF3-) neurons. Spinal nerve ligation increased the expression of P2X3Rs. Electroacupuncture reduced the increase in P2X3R expression without affecting the percentage of ATF + neurons. In ipsilateral L5 dorsal root ganglion neurons, spinal nerve ligation reduced the percentage of P2X3R + neurons and markedly increased the percentage of ATF3 + cells. Almost all of P2X3Rs were expressed in damaged (ATF3+) neurons. Electroacupuncture had no effect on spinal nerve ligation-induced changes in the percentage of P2X3R or percentage of ATF3 + cells in L5 dorsal root ganglia. These observations led us to conclude that electroacupuncture effectively reduces injury-induced chronic pain by selectively reducing the expression of P2X3Rs in nerve-uninjured L4 dorsal root ganglion neurons.
Topics: Activating Transcription Factor 3; Adenosine Triphosphate; Animals; Down-Regulation; Electroacupuncture; Ganglia, Spinal; Hyperalgesia; Ligation; Lumbar Vertebrae; Male; Neurons; Rats, Sprague-Dawley; Receptors, Purinergic P2X3; Spinal Nerves
PubMed: 30983496
DOI: 10.1177/1744806919847810 -
European Journal of Pharmacology Aug 2008Nicotinic acetylcholine receptors are widely expressed in the rat spinal cord and modulate innocuous and nociceptive transmission. The present studies were designed to...
Nicotinic acetylcholine receptors are widely expressed in the rat spinal cord and modulate innocuous and nociceptive transmission. The present studies were designed to investigate the plasticity of spinal nicotinic acetylcholine receptors modulating mechanosensitive information following spinal nerve ligation. A tonic inhibitory cholinergic tone mediated by dihydro-beta-erythroidine- (DHbetaE) and methyllycaconitine- (MLA) sensitive nicotinic acetylcholine receptors was identified in the normal rat spinal cord and cholinergic tone at both populations of nicotinic acetylcholine receptors was lost ipsilateral to spinal nerve ligation. The administration of intrathecal nicotinic acetylcholine receptor agonists reduced mechanical paw pressure thresholds with a potency of epibatidine=A-85380>>nicotine>choline in the normal rat. Following spinal nerve ligation, intrathecal epibatidine and nicotine produced an ipsilateral antinociception, but intrathecal A-85380 and choline did not. The antinociceptive response to intrathecal nicotine was blocked with the alpha7 and alpha9alpha10-selective nicotinic acetylcholine receptor antagonist, MLA, and the alphabeta heteromeric nicotinic acetylcholine receptor antagonist, DHbetaE. The antinociceptive effects of both intrathecal nicotine and epibatidine were mediated by GABA(A) receptors. Spinal [(3)H]epibatidine saturation binding was unchanged in spinal nerve-ligated rats, but spinal nerve ligation did increase the ability of nicotine to displace [(3)H]epibatidine from spinal cord membranes. Spinal nerve ligation altered the expression of nicotinic acetylcholine receptor subunits ipsilaterally, with a large increase in the modulatory alpha5 subunit. Taken together these results suggest that pro- and antinociceptive populations of spinal nicotinic acetylcholine receptors modulate the transmission of mechanosensitive information and that spinal nerve ligation-induced changes in spinal nicotinic acetylcholine receptors likely result from a change in subunit composition rather than overt loss of nicotinic acetylcholine receptor subtypes.
Topics: Animals; Bridged Bicyclo Compounds, Heterocyclic; Male; Nicotine; Pain; Peripheral Nervous System Diseases; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic; Spinal Cord; Spinal Nerves; gamma-Aminobutyric Acid
PubMed: 18573248
DOI: 10.1016/j.ejphar.2008.06.020 -
Anatomical Record (Hoboken, N.J. : 2007) Aug 2015The detailed morphology and topography of the cranial cervical ganglion (CCG) with its surrounding structures were studied in 10 sides of five heads of adult one-humped...
The detailed morphology and topography of the cranial cervical ganglion (CCG) with its surrounding structures were studied in 10 sides of five heads of adult one-humped camel to determine its general arrangement as well as its differences and similarities to other animals. The following detailed descriptions were obtained: (1) the bilateral CCG was constantly present caudal to cranial base at the rostroventral border of the occipital condyle over the caudolateral part of nasopharynx; (2) the CCG was always in close relations medially with the longus capitis muscle, rostrolaterally with the internal carotid artery, and caudally with the vagus nerve; and (3) the branches of the CCG were the internal carotid and external carotid nerves, jugular nerve, cervical interganglionic branch, laryngopharyngeal branch, carotid sinus branch and communicating branches to the vagus, and first spinal nerves. In conclusion, there was no variation regarding topography of dromedary CCG among the specimens, in spite of typical variations in number, and mainly in origin of nerve branches ramifying from the CCG. In comparative anatomy aspect, the close constant relations, and presence of major nerves (internal/external carotid and jugular nerves) of dromedary CCG exhibited a typical reported animal's pattern. However, the shape, structures lateral to the CCG, the origin and course pattern of external carotid and jugular nerves, the number of the major nerves branches, the communicating branches of the CCG to the spinal and cranial nerves, and the separation of most rostral parts of vagosympathetic trunk of dromedary were different from those of most reported animals.
Topics: Animals; Camelus; Cranial Nerves; Head; Male; Spinal Nerves; Superior Cervical Ganglion
PubMed: 25950508
DOI: 10.1002/ar.23169 -
Molecular Pain Dec 2012Our previous studies have indicated that both lumbar spinal cord-infiltrating CD4+ T cells and microglial CD40 contribute to the maintenance of mechanical...
BACKGROUND
Our previous studies have indicated that both lumbar spinal cord-infiltrating CD4+ T cells and microglial CD40 contribute to the maintenance of mechanical hypersensitivity in a murine model of neuropathic pain spinal nerve L5 transection (L5Tx). To further delineate the CD4 and CD40-mediated mechanisms involved in the development of L5Tx-induced neuropathic pain behaviors, we examined the lumbar spinal cord mononuclear cells of wild type (WT) BALB/c, BALB/c-CD4 knockout (KO), and BALB/c-CD40 KO mice via flow cytometry.
RESULTS
In WT mice, L5Tx induced significant but transient (at day 3 and/or day 7) increases of the total numbers of mononuclear cells, microglial cells (CD45loCD11b+), and infiltrating leukocytes (CD45hi) in the ipsilateral side of the spinal cord. In CD4 KO mice, significant elevation of microglia was detected only on day 7 post-L5Tx, while no significant increase in infiltrating leukocytes post-L5Tx was observed. CD40 KO mice did not exhibit any of the changes observed in WT mice. Furthermore, neutralizing CD40 antibody treatment indicated an early involvement of CD40 signaling in the development of L5Tx-induced mechanical hypersensitivity.
CONCLUSIONS
Altogether, data indicate that both CD4 and CD40 play a role in L5Tx-induced leukocyte infiltration into the lumbar spinal cord but have differential contributions to spinal cord microglial activation following peripheral nerve injury.
Topics: Animals; CD4-Positive T-Lymphocytes; CD40 Antigens; Female; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Microglia; Neuralgia; Spinal Nerves
PubMed: 23249743
DOI: 10.1186/1744-8069-8-88 -
Yonsei Medical Journal Sep 2015The TWIK-related spinal cord K⁺ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there...
PURPOSE
The TWIK-related spinal cord K⁺ channel (TRESK) has recently been discovered and plays an important role in nociceptor excitability in the pain pathway. Because there have been no reports on the TRESK expression or its function in the dorsal horn of the spinal cord in neuropathic pain, we analyzed TRESK expression in the spinal dorsal horn in a spinal nerve ligation (SNL) model.
MATERIALS AND METHODS
We established a SNL mouse model by using the L5-6 spinal nerves ligation. We used real-time polymerase chain reaction and immunohistochemistry to investigate TRESK expression in the dorsal horn and L5 dorsal rot ganglion (DRG).
RESULTS
The SNL group showed significantly higher expression of TRESK in the ipsilateral dorsal horn under pain, but low expression in L5 DRG. Double immunofluorescence staining revealed that immunoreactivity of TRESK was mostly restricted in neuronal cells, and that synapse markers GAD67 and VGlut2 appeared to be associated with TRESK expression. We were unable to find a significant association between TRESK and calcineurin by double immunofluorescence.
CONCLUSION
TRESK in spinal cord neurons may contribute to the development of neuropathic pain following injury.
Topics: Animals; Disease Models, Animal; Hyperalgesia; Ligation; Male; Neuralgia; Neurons; Nociceptors; Pain; Potassium Channels; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Spinal Cord Dorsal Horn; Spinal Nerves
PubMed: 26256973
DOI: 10.3349/ymj.2015.56.5.1307 -
Clinical Gastroenterology and... Oct 2023
Topics: Humans; Gastroparesis; Spinal Nerves; Gastric Emptying; Diabetes Mellitus
PubMed: 36152902
DOI: 10.1016/j.cgh.2022.09.012 -
Scientific Reports Nov 2016Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and...
Nerve injury-induced downregulation of voltage-gated potassium channel subunit Kcna2 in the dorsal root ganglion (DRG) is critical for DRG neuronal excitability and neuropathic pain genesis. However, how nerve injury causes this downregulation is still elusive. Euchromatic histone-lysine N-methyltransferase 2, also known as G9a, methylates histone H3 on lysine residue 9 to predominantly produce a dynamic histone dimethylation, resulting in condensed chromatin and gene transcriptional repression. We showed here that blocking nerve injury-induced increase in G9a rescued Kcna2 mRNA and protein expression in the axotomized DRG and attenuated the development of nerve injury-induced pain hypersensitivity. Mimicking this increase decreased Kcna2 mRNA and protein expression, reduced Kv current, and increased excitability in the DRG neurons and led to spinal cord central sensitization and neuropathic pain-like symptoms. G9a mRNA is co-localized with Kcna2 mRNA in the DRG neurons. These findings indicate that G9a contributes to neuropathic pain development through epigenetic silencing of Kcna2 in the axotomized DRG.
Topics: Action Potentials; Animals; Axotomy; Cells, Cultured; Down-Regulation; Ganglia, Spinal; Histone-Lysine N-Methyltransferase; Histones; Hypersensitivity; Ion Channel Gating; Kv1.2 Potassium Channel; Ligation; Lysine; Male; Methylation; Mice, Inbred C57BL; Neuralgia; RNA, Messenger; Sensory Receptor Cells; Spinal Nerves
PubMed: 27874088
DOI: 10.1038/srep37704