1.Localization of sympathetic and sensory nerves innervating heart in the cat using HRP and WGA-HRP as neuronal tracers.
Eui Hyeog HAN ; Chang Hyun LEE ; Hyoung Tae KIM ; Moo Sam LEE
Korean Journal of Anatomy 2000;33(2):229-239
The origin of sympathetic and sensory nerves innervating heart in the cat was investigated using HRP (Horseradish peroxidase) and WGA-HRP (Wheat germ agglutinin-horseradish peroxidase) as neuronal tracers. The neural tracers were injected into subepicardial layer and myocardium of the right atrium, left atrium, right ventricle and left ventricle, respectively. Labeled sympathetic neuronal cell bodies were found in superior cervical ganglia, middle cervical ganglia, stellate ganglia and 4th and 5th thoracic ganglia, mainly in middle cervical ganglia and stellate ganglia. Heavier labeled neuronal cell bodies were found in the middle cervical ganglia and stellate ganglia when the neural tracers were injected into left atrium, right ventricle and left ventricle. Labeled sensory neuronal cell bodies were found in nodose ganglia and T1-T6 spinal ganglia, mainly in T1-T5 spinal ganglia. Heavier labeled neuronal cell bodies were found in the nodose ganglia when the neural tracers were injected into left atrium and right ventricle. These results may provide a neuroanatomical data on origin of sensory nerves innervating the heart of the cat.
Animals
;
Cats*
;
Ganglia
;
Ganglia, Sensory
;
Ganglia, Spinal
;
Ganglia, Sympathetic
;
Heart Atria
;
Heart Ventricles
;
Heart*
;
Horseradish Peroxidase
;
Myocardium
;
Neurons*
;
Nodose Ganglion
;
Sensory Receptor Cells
;
Stellate Ganglion
;
Superior Cervical Ganglion
;
Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate*
2.R-type Calcium Channel Isoform in Rat Dorsal Root Ganglion Neurons.
Zhi FANG ; Jae Hong HWANG ; Joong Soo KIM ; Sung Jun JUNG ; Seog Bae OH
The Korean Journal of Physiology and Pharmacology 2010;14(1):45-49
R-type Cav2.3 high voltage-activated Ca2+ channels in peripheral sensory neurons contribute to pain transmission. Recently we have demonstrated that, among the six Cav2.3 isoforms (Cav2.3a~Cav2.3e), the Cav2.3e isoform is primarily expressed in trigeminal ganglion (TG) nociceptive neurons. In the present study, we further investigated expression patterns of Cav2.3 isoforms in the dorsal root ganglion (DRG) neurons. As in TG neurons, whole tissue RT-PCR analyses revealed the presence of two isoforms, Cav2.3a and Cav2.3e, in DRG neurons. Single-cell RT-PCR detected the expression of Cav2.3e mRNA in 20% (n=14/70) of DRG neurons, relative to Cav2.3a expression in 2.8% (n=2/70) of DRG neurons. Cav2.3e mRNA was mainly detected in small-sized neurons (n=12/14), but in only a few medium-sized neurons (n=2/14) and not in large-sized neurons, indicating the prominence of Cav2.3e in nociceptive DRG neurons. Moreover, Cav2.3e was preferentially expressed in tyrosine-kinase A (trkA)-positive, isolectin B4 (IB4)-negative and transient receptor potential vanilloid 1 (TRPV1)-positive neurons. These results suggest that Cav2.3e may be the main R-type Ca2+ channel isoform in nociceptive DRG neurons and thereby a potential target for pain treatment, not only in the trigeminal system but also in the spinal system.
Animals
;
Calcium Channels, R-Type
;
Diagnosis-Related Groups
;
Ganglia, Spinal
;
Lectins
;
Neurons
;
Nociceptors
;
Protein Isoforms
;
Rats
;
RNA, Messenger
;
Sensory Receptor Cells
;
Spinal Nerve Roots
;
Trigeminal Ganglion
3.Segmental Zoster Paresis Showing Spinal Nerve Roots Involvement on Gadolinium-Enhanced MRI.
Jae Hwan CHOI ; Sung Ho AHN ; Young Eun PARK ; Dae Seong KIM
Journal of the Korean Neurological Association 2006;24(3):274-277
Segmental zoster paresis is a focal, asymmetric limb weakness caused by a herpes zoster infection. It is a rare complication of herpes zoster and the exact pathogenesis is uncertain. However, the most likely cause is the direct spread of the virus from the sensory ganglia to the anterior horn cells or anterior spinal nerve roots. We experienced two patients with segmental zoster paresis who showed both anterior and posterior root involvement on a gadolinium-enhanced MRI, supporting this hypothesis.
Anterior Horn Cells
;
Extremities
;
Ganglia, Sensory
;
Herpes Zoster*
;
Humans
;
Magnetic Resonance Imaging*
;
Neuroimaging
;
Paresis*
;
Spinal Nerve Roots*
;
Spinal Nerves*
4.Somatosensory Neuron Typing with High-Coverage Single-Cell RNA Sequencing and Functional Analysis.
Changlin LI ; Sashuang WANG ; Yan CHEN ; Xu ZHANG
Neuroscience Bulletin 2018;34(1):200-207
Different physical and chemical stimuli are detected by the peripheral sensory receptors of dorsal root ganglion (DRG) neurons, and the generated inputs are transmitted via afferent fibers into the central nervous system. The gene expression profiles of DRG neurons contribute to the generation, transmission, and regulation of various somatosensory signals. Recently, the single-cell transcriptomes, cell types, and functional annotations of somatosensory neurons have been studied. In this review, we introduce our classification of DRG neurons based on single-cell RNA-sequencing and functional analyses, and discuss the technical approaches. Moreover, studies on the molecular and cellular mechanisms underlying somatic sensations are discussed.
Animals
;
Ganglia, Spinal
;
cytology
;
Gene Regulatory Networks
;
Humans
;
Pain
;
genetics
;
metabolism
;
pathology
;
Sensory Receptor Cells
;
metabolism
;
Sequence Analysis, RNA
;
Transcriptome
5.Localization of Sensory Neurons Innervating the Rat Intestine Using the Cholera Toxin B Subunit(CTB) and Wheat Germ Agglutinin-Horseradish Peroxidase(WGA-HRP).
Dong Hyup LEE ; Chang Hyun LEE ; Moo Sam LEE
Yeungnam University Journal of Medicine 1998;15(1):75-96
The local arrangement of sensory nerve cell bodies and nerve fibers in the brain stem, spinal ganglia and nodose ganglia were observed following injection of cholera toxin B subunit(CTB) and wheat germ agglutinin-horseradish peroxidase(WGA-HRP) into the rat intestine. The tracers were injected in the stomach(anterior and posterior portion), duodenum, jejunum, ileum, cecum, ascending colon or descending colon. After survival times of 48-96 hours, the rats were perfused and their brain, spinal and nodose ganglia were frozen sectioned(40microM). These sectiones were stained by CTB immunohistochemical and HRP histochemical staining methods and observed by dark and light microscopy. The results were as follows: 1. WGA-HRP labeled afferent terminal fields in the brain stem were seen in the stomach and cecum, and CTB labeled afferent terminal fields in the brain stem were seen in all parts of the intestine. 2. Afferent terminal fields innervating the intestine were heavily labeled bilaterally gelalinous part of nucleus of tractus solitarius(gelNTS), dorsomedial part of gelNTS, commissural part of NTS(comNTS), medial part of NTS(medNTS), wall of the fourth ventricle, ventral border of area postrema and comNTS in midline dorsal to the central canal. 3. WGA-HRP labeled sensory neurons were observed bilaterally within the spinal ganglia, and labeled sensory neurons innervating the stomach were observed in spinal ganglia T2-L1 and the most numerous in spinal ganglia T8-9. 4. Labeled sensory neurons innervating the duodenum were observed in spinal ganglia T6-L2 and labeled cell number were fewer than the other parts of the intestines. 5. Labeled sensory neurons innervating the jejunum were observed in spinal ganglia T6-L2 and the most numerous area in the spinal ganglia were T12 in left and T13 in right. 6. Labeled sensory neurons innervating the ileum were observed in spinal ganglia T6-L2 and the most numerous area in the spinal ganglia were T11 in left and L1 in right. 7. Labeled sensory neurons innervating the cecum were observed in spinal ganglia T7-L2 and the most numerous area in the spinal ganglia were T11 in left and T11-12 in right. 8. Labeled sensory neurons innervating the ascending colon were observed in spinal ganglia T7-L2 in left, and T9-L4 in right. The most numerous area in the spinal ganglia were T9 in left and T11 in right. 9. Labeled sensory neurons innervating the descending colon were observed in spinal ganglia T9-L2 in left, and T6-L2 in right. The most numerous area in the spinal ganglia were T13 in left and L1 in right. 10. WGA-HRP labeled sensory neurons were observed bilaterally within the nodose ganglia, and the most numerous labeled sensory neurons innervating the abdominal organs were observed in the stomach. 11. The number of labeled sensory neurons within the nodose ganglia innervating small and large intestines were fewer than that of labeled sensory neurons innervating stomach These results indicated that area of sensory neurons innervated all parts of intestines were bilaterally gelatinous part of nucleus tractus solitarius(gelNTS), dorsomedial part of gelNTS, commissural part of NTS(comNTS), medial part of NTS, wall of the fourth ventricle, ventral border of area postrema and com NTS in midline dorsal to the central canal within brain stem, spinal ganglia T2-L4, and nodose ganglia. Labeled sensory neurons innervating the intestines except the stomach were observed in spinal ganglia T6-L4. The most labeled sensory neurons from the small intestine to large intestine came from middle thoracic spinal ganglia to upper lumbar spinal ganglia.
Animals
;
Area Postrema
;
Brain
;
Brain Stem
;
Cecum
;
Cell Count
;
Cholera Toxin*
;
Cholera*
;
Colon, Ascending
;
Colon, Descending
;
Duodenum
;
Fourth Ventricle
;
Ganglia, Spinal
;
Gelatin
;
Ileum
;
Intestine, Large
;
Intestine, Small
;
Intestines*
;
Jejunum
;
Microscopy
;
Nerve Fibers
;
Neurons
;
Nodose Ganglion
;
Rats*
;
Sensory Receptor Cells*
;
Stomach
;
Triticum*
;
Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate
6.Evaluation of Histological Changes in Back Muscle Injuries in Rats over Time.
Koki ABE ; Kazuhide INAGE ; Yoshihiro SAKUMA ; Sumihisa ORITA ; Kazuyo YAMAUCHI ; Miyako SUZUKI ; Go KUBOTA ; Yasuhiro OIKAWA ; Takeshi SAINOH ; Jun SATO ; Kazuki FUJIMOTO ; Yasuhiro SHIGA ; Hirohito KANAMOTO ; Kazuhisa TAKAHASHI ; Seiji OHTORI
Asian Spine Journal 2017;11(1):88-92
STUDY DESIGN: Animal model study. PURPOSE: The purpose of this study was to evaluate the histological variation in the injured muscle and production of calcitonin gene-related peptide in rats over time. OVERVIEW OF LITERATURE: Vertebral surgery has been reported to cause atrophy of the back muscles, which may result in pain. However, few reports have described the time series histological variation in the injured muscle and changes in the dominant nerve. METHODS: We used 30 male, 8-week-old Sprague-Dawley rats. The right and left sides of the paravertebral muscle were considered as the injured and uninjured sides, respectively. A 115 g weight was dropped from a height of 1 m on the right paravertebral muscle. Hematoxylin and eosin (H&E) staining of the muscle was performed 1–3 weeks after injury for histological evaluation. Fluoro-Gold (FG) was injected into the paravertebral muscle. The L2 dorsal root ganglia on both sides were resected 1, 2, and 3 weeks after injury, and immunohistochemical staining for calcitonin gene-related peptide was performed. RESULTS: H&E staining of the paravertebral muscle showed infiltration of inflammatory cells and the presence of granulation tissue in the injured part on the ipsilateral side 1 week after injury. Muscle atrophy occurred 3 weeks after injury, but was repaired via spontaneous replacement of muscle cells/fibers. In contrast, compared with the uninjured side, the percentage of cells double-labeled with FG and calcitonin gene-related peptide in FG-positive cells in the dorsal root ganglia of the injured side was significantly increased at each time point throughout the study period. CONCLUSIONS: These results suggest that sensitization of the dominant nerve in the dorsal root ganglia, which may be caused by cicatrix formation, can protract injured muscle pain. This information may be helpful in elucidating the underlying mechanism of persistent pain after back muscle injury.
Animals
;
Atrophy
;
Back Muscles*
;
Calcitonin Gene-Related Peptide
;
Cicatrix
;
Eosine Yellowish-(YS)
;
Ganglia, Sensory
;
Ganglia, Spinal
;
Granulation Tissue
;
Hematoxylin
;
Humans
;
Male
;
Models, Animal
;
Muscular Atrophy
;
Myalgia
;
Rats*
;
Rats, Sprague-Dawley
;
Spine
7.Effects of Fluoxetine on Sodium Currents in Rat Sensory Neurons.
Hyun Wook HA ; Jeong Ho HAN ; Yoon Young JANG ; Yong Kyoo SHIN ; Chung Soo LEE ; Jin Ho SONG
Journal of the Korean Neurological Association 2000;18(6):754-763
BACKGROUND: Fluoxetine, a widely used antidepressant drug, has been described as a selective serotonin reuptake inhibitor. In addition to its antidepressant action it has been demonstrated to be effective in alleviating pain associated with various diseases. Dorsal root ganglion (DRG) neurons are primary sensory neurons and transmit peripheral information to central nervous system. Two types of sodium channels are expressed in DRG neurons based on their sensitivity to tetrodotoxin. They are involved in the generation and conduction of nociception. The effects of fluoxetine on sodium currents in DRG neurons were examined to elucidate the analgesic mechanism of the drug. METHODS: DRG neurons wereacutely dissociated from rats (2~6 days postnatal) by enzymatic digestion. The whole-cell configuration of patch clamp technique was used to record tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) sodium currents. RESULTS: Fluoxetine inhibited TTX-S and TTX-R sodium currents with Kd values of 60 microM and 59 microM, respectively, at the holding potential of -80 mV. For both types of sodium channels the steady-state inactivation curves were shifted in the hyperpolarizing direction and the conductance-voltage relationship curves were shifted in the depolarizing direction by fluoxetine. These effects combined together would greatly reduce the neuronal excitability. CONCLUSIONS: The blockade of sodium currents in sensory neurons is considered as a possible mechanism for the analgesic action of fluoxetine.
Animals
;
Central Nervous System
;
Diagnosis-Related Groups
;
Digestion
;
Fluoxetine*
;
Ganglia, Spinal
;
Neurons
;
Nociception
;
Rats*
;
Sensory Receptor Cells*
;
Serotonin
;
Sodium Channels
;
Sodium*
;
Tetrodotoxin
8.Effects of Capsaicin on the Primary Sensory Neurons in Rat.
Jeong Gill LEEM ; Kwang Il SHIN
Korean Journal of Anesthesiology 1998;35(4):642-653
BACKGREOUND: Capsaicin acts specifically on a subset of primary sensory neurons involved in nociception. In addition to its excitatory actions, capsaicin can have subsequent antinociception and anti-inflammatory effects due to pharmacological, functional desensitization and axonal degeneration. Because capsaicin has selective actions on unmyelinated C and thinly myelinated Adelta primary sensory neurons, it can be speculated that intrathecally adminstered capsaicin results prolonged analgesia without adverse effects related to the destruction of the nonnociceptive nerve fibers. METHODS: We performed experiments to investigate the effects of capsaicin on electrophysiological responses of acutely dissociated rat dorsal root ganglion neurons and pain-like behaviors, such as tail flick responses to hot water (53 degrees), formalin-induced hyperalgesic responses and allodynic responses induced by peripheral nerve injury. RESULTS: Capsaicin affects preferentially small- to medium-diameter rat dorsal root ganglion neurons. In capsaicin responsive cells, superfusion with capsaicin evoked membrane potential depolarization and large inward currents. Cellular excitablity was continuously suppressed even after 3 min wash-out. Intrathecally administered capsaicin had no effect on tail withdrawal latencies, but flinching responses induced by subcutaneous formalin and allodynic responses induced by peripheral nerve injury were suppressed by capsaicin. CONCLUSIONS: The results suggest that capsaicin which acts on primary sensory neurons carrying nociceptive information is effective in managing pain induced in a pathological condition, such as inflammatory and neuropathic pain. The data may also be applicable for seeking novel pharmacological strategies for managing intractable pain, i.e. chemical neurolysis.
Analgesia
;
Animals
;
Axons
;
Capsaicin*
;
Formaldehyde
;
Ganglia, Spinal
;
Membrane Potentials
;
Myelin Sheath
;
Nerve Block
;
Nerve Fibers
;
Neuralgia
;
Neurons
;
Nociception
;
Pain, Intractable
;
Peripheral Nerve Injuries
;
Rats*
;
Sensory Receptor Cells*
;
Water
9.Nimodipine as a potential pharmacological tool for characterizing R-type calcium currents.
The Korean Journal of Physiology and Pharmacology 2001;5(6):511-519
Nimopidine, one of dihydropyridine derivatives, has been widely used to pharmacologically identify L-type Ca currents. In this study, it was tested if nimodipine is a selective blocker for L-type Ca currents in sensory neurons and heterologous system. In mouse dorsal root ganglion neurons (DRG), low concentrations of nimodipine (<10 muM), mainly targeting L-type Ca currents, blocked high-voltage-activated calcium channel currents by apprx38%. Interestingly, high concentrations of nimodipine (>10 muM) further reduced the "residual" currents in DRG neurons from alpha1E knock-out mice, after blocking L-, N- and P/Q-type Ca currents with 10 muM nimodipine, 1 muM omega-conotoxin GVIA and 200 nM omega-agatoxin IVA, indicating inhibitory effects of nimodipine on R-type Ca currents. Nimodipine (>10 muM) also produced the inhibition of both low-voltage-activated calcium channel currents in DRG neurons and alpha1B and alpha1E subunit based Ca channel currents in heterologous system. These results suggest that higher nimodipine (>10 muM) is not necessarily selective for L-type Ca currents. While care should be taken in using nimodipine for pharmacologically defining L-type Ca currents from native macroscopic Ca currents, nimodipine (>10 muM) could be a useful pharmacological tool for characterizing R-type Ca currents when combined with toxins blocking other types of Ca channels.
Animals
;
Calcium Channels
;
Calcium*
;
Diagnosis-Related Groups
;
Ganglia, Spinal
;
Mice
;
Mice, Knockout
;
Neurons
;
Nimodipine*
;
omega-Agatoxin IVA
;
omega-Conotoxin GVIA
;
Sensory Receptor Cells
10.Growth Differentiation Factor-15 Produces Analgesia by Inhibiting Tetrodotoxin-Resistant Nav1.8 Sodium Channel Activity in Rat Primary Sensory Neurons.
Wei LIN ; Wen-Wen ZHANG ; Ning LYU ; Hong CAO ; Wen-Dong XU ; Yu-Qiu ZHANG
Neuroscience Bulletin 2021;37(9):1289-1302
Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.
Analgesia
;
Animals
;
Ganglia, Spinal
;
Growth Differentiation Factor 15
;
NAV1.8 Voltage-Gated Sodium Channel
;
Rats
;
Sensory Receptor Cells
;
Sodium Channels
;
Tetrodotoxin/pharmacology*