2.A role for uninjured afferents in neuropathic pain.
Richard A MEYER ; Matthias RINGKAMP
Acta Physiologica Sinica 2008;60(5):605-609
Diseases and injuries to the nervous system can lead to a devastating chronic pain condition called neuropathic pain. We review changes that occur in the peripheral nervous system that may play a role in this disease. Common animal models for neuropathic pain involve an injury to one or more peripheral nerves. Following such an injury, the nerve fibers that have been injured exhibit many abnormal properties including the development of spontaneous neural activity as well as a change in the expression of certain genes in their cell body. Recent data indicate that adjacent, uninjured nerve fibers also exhibit significant changes. These changes are thought to be driven by injury-induced alterations in the milieu surrounding the uninjured nerve and nerve terminals. Thus, alteration in neural signaling in both injured and uninjured neurons play a role in the development of neuropathic pain after peripheral nerve injury.
Animals
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Disease Models, Animal
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Nerve Fibers
;
pathology
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Neuralgia
;
physiopathology
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Neurons, Afferent
;
cytology
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Peripheral Nerve Injuries
;
physiopathology
3.Expression of Fos Protein in Brainstem Vestibular Nuclei of Rat-II. Sinusoidal Acceleration Stimulation-.
Han Kyu SUH ; Jeong Su WOO ; Ho Jeong PARK ; Dong Hee YOO ; Eun Soo LEE ; Hyun Ho LIM ; Soon Jae HWANG
Korean Journal of Otolaryngology - Head and Neck Surgery 1998;41(12):1513-1520
BACKGROUND AND OBJECTIVES: Fos, the protein product of c-fos gene, has been known to be rapidly expressed in neurons following various external and internal stimuli and this protein expression has been used as a neural activation marker in many fields. This experiment was performed to examine the afferent pathway of the lateral semicircular canals following sinusoidal acceleration. MATERIALS & METHODS: To stimulate the lateral semicircular canals, animals received rotary stimulation for 90 minutes with 2.0Hz sinusoidal acceleration. Thirty minutes after stimulation, the subjects were sacrificed and their brainstems were processed for immunohistochemistry to detect Fos expression. RESULTS: Fos proteins were strongly expressed in the superior, dorsal medial vestibular and inferior vestibular nuclei. However, there was no expression in the lateral and ventral portion of medial vestibular nuclei. CONCLUSION: This finding suggested that the afferent pathway from peripheral vestibular end-organ can be successfully mapped by detection of Fos expression and Fos is an useful neural activity marker in the vestibular system.
Acceleration*
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Afferent Pathways
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Animals
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Brain Stem*
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Genes, fos
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Immunohistochemistry
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Neurons
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Semicircular Canals
;
Vestibular Nuclei*
4.Location of somatic sensory neurons of the skin and dorsal nerve of the penis in rabbits.
Bao-Jin WU ; Hua JIANG ; Wen-Peng LI ; Ying-Fan ZHANG ; Gang CHEN
National Journal of Andrology 2007;13(1):17-20
OBJECTIVETo trace the segmental distribution of somatic sensory neurons of the skin and dorsal nerve in the rabbitś penis.
METHODSThe experiment was performed on 8 adult male rabbits with the nerve tracing method of retrograde axonal transport of horseradish peroxidase (HRP), which was injected into the dermis around the penis and the dorsal nerve of the penis. The rabbits were sacrificed five days later to harvest the spinal cord segments and the dorsal root ganglia of lumbosacral segments for histological study.
RESULTSThe HRP tracing showed that a number of labeled HRP positive neurons appeared in spinal ganglia (S2 - S4) in all the rabbits, and distributed segmentally. The counts of the positive neurons different segments were: S2 (215.0 +/- 10.2) , S3 (242.2 +/- 8.3) and S4 (109.7 +/- 8.4) respectively, with statistically significant difference between the two groups.
CONCLUSIONThe rabbit's sensory nerve fibers in both the skin and the dorsal nerve of the penis are rooted in the S2-S4 segments of spinal ganglia, which distribute regularly.
Animals ; Anterior Horn Cells ; anatomy & histology ; Biomarkers ; Male ; Neurons, Afferent ; Neurons, Efferent ; Penis ; innervation ; Rabbits ; Random Allocation ; Skin ; innervation
5.Effect of carbamazepine on tetrodotoxin-resistant Na⁺ channels in trigeminal ganglion neurons innervating to the dura.
Jin Eon HAN ; Jin Hwa CHO ; Michiko NAKAMURA ; Maan Gee LEE ; Il Sung JANG
The Korean Journal of Physiology and Pharmacology 2018;22(6):649-660
Migraine is a neurological disorder characterized by recurrent and disabling severe headaches. Although several anticonvulsant drugs that block voltage-dependent Na⁺ channels are widely used for migraine, far less is known about the therapeutic actions of carbamazepine on migraine. In the present study, therefore, we characterized the effects of carbamazepine on tetrodotoxin-resistant (TTX-R) Na⁺ channels in acutely isolated rat dural afferent neurons, which were identified by the fluorescent dye DiI. The TTX-R Na⁺ currents were measured in medium-sized DiIpositive neurons using the whole-cell patch clamp technique in the voltage-clamp mode. While carbamazepine had little effect on the peak amplitude of transient Na⁺ currents, it strongly inhibited steady-state currents of transient as well as persistent Na⁺ currents in a concentration-dependent manner. Carbamazepine had only minor effects on the voltage-activation relationship, the voltage-inactivation relationship, and the use-dependent inhibition of TTX-R Na⁺ channels. However, carbamazepine changed the inactivation kinetics of TTX-R Na⁺ channels, significantly accelerating the development of inactivation and delaying the recovery from inactivation. In the current-clamp mode, carbamazepine decreased the number of action potentials without changing the action potential threshold. Given that the sensitization of dural afferent neurons by inflammatory mediators triggers acute migraine headaches and that inflammatory mediators potentiate TTX-R Na⁺ currents, the present results suggest that carbamazepine may be useful for the treatment of migraine headaches.
Action Potentials
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Animals
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Anticonvulsants
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Carbamazepine*
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Headache
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Kinetics
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Migraine Disorders
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Nervous System Diseases
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Neurons*
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Neurons, Afferent
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Rats
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Sodium Channels
;
Trigeminal Ganglion*
6.Expression of growth hormone secretagogue receptor type 1a in visceral vagal and spinal afferent pathways.
Yun-Dan JIA ; Xi CHEN ; Ming TANG ; Zheng-Yao JIANG
Acta Physiologica Sinica 2008;60(1):149-155
In this study, the expressions of growth hormone secretagogue receptor type 1a (GHS-R1a) in the rat dorsal root ganglion (DRG) and nodose ganglion (NG) were investigated by using immunohistochemistry and in situ hybridization. The results clearly showed the presence of GHS-R1a mRNA and GHS-R1a-positive neurons in the rat DRG and NG. GHS-R1a was also co-localized with calcitonin gene-related peptide (CGRP) in some DRG and NG neurons, indicating the existence of subpopulations of the visceral afferents. The extrinsic primary afferent visceroceptive DRG and NG neurons from the stomach were identified by retrograde tracing fluorogold and stained for GHS-R1a and CGRP. Some neurons both positive for CGRP and GHS-Rla were labled by fluorogold. Our results not only demonstrate the expression of GHS-R1a in the vagal afferents but also provide the first and direct morphological evidence for its presence in the spinal visceral afferents, and gherin might have a modulatory role in the visceral afferent signaling.
Afferent Pathways
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Animals
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Calcitonin Gene-Related Peptide
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metabolism
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Ganglia, Spinal
;
cytology
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Immunohistochemistry
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Neurons, Afferent
;
cytology
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Nodose Ganglion
;
cytology
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Rats
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Receptors, Ghrelin
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metabolism
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Stomach
;
innervation
7.Vanilloid Receptor Type-1 Immunoreactivities in the Mouse Myenteric Plexus: Immunohistochemical and Electrophysiological Study.
Jae Yeoul JUN ; En Seok YANG ; Kee Hune KIM ; In Youb CHANG
Korean Journal of Physical Anthropology 2004;17(1):45-53
The vanilloid receptor type-1 (VR1) is a nonselective cation channel activated by capsaicin and can be act as mediator of chemical and physical stimuli that elicit pain. The presence of VR1 in the dorsal root, trigeminal and nodose ganglia has been firmly established, but it unclear in the mouse intestinal wall. The distribution of VR1 receptors in mouse afferent neurons innervating the intestinal tract was investigated by immunohistochemistry. Also small and large intestines were dual-labelled with antibody for VR1 and marker for interstitial cells of Cajal (c-kit). VR1-immunopositive cells were localized on fine fibers in myenteric plexus and expressed weakly myenteric ganglia. The majority of VR1-immunopositive fibers are not colocalized with or apposed to c-kit positive interstitial cells of Cajal. Also electrophysiologically capsaicin had no effect on cultured interstitial cells of Cajal. It is concluded that VR1-immunoreactive intestinal nerves are mainly distributed in myenteric plexus of murine intestinal wall, and vanillod may be not directly related to interstitial cells of Cajal in regulation of intestinal motility.
Animals
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Capsaicin
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Ganglia
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Gastrointestinal Motility
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Immunohistochemistry
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Interstitial Cells of Cajal
;
Intestines
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Mice*
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Myenteric Plexus*
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Neurons, Afferent
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Nodose Ganglion
;
Spinal Nerve Roots
8.Vanilloid Receptor Type-1 Immunoreactivities in the Mouse Myenteric Plexus: Immunohistochemical and Electrophysiological Study.
Jae Yeoul JUN ; En Seok YANG ; Kee Hune KIM ; In Youb CHANG
Korean Journal of Physical Anthropology 2004;17(1):45-53
The vanilloid receptor type-1 (VR1) is a nonselective cation channel activated by capsaicin and can be act as mediator of chemical and physical stimuli that elicit pain. The presence of VR1 in the dorsal root, trigeminal and nodose ganglia has been firmly established, but it unclear in the mouse intestinal wall. The distribution of VR1 receptors in mouse afferent neurons innervating the intestinal tract was investigated by immunohistochemistry. Also small and large intestines were dual-labelled with antibody for VR1 and marker for interstitial cells of Cajal (c-kit). VR1-immunopositive cells were localized on fine fibers in myenteric plexus and expressed weakly myenteric ganglia. The majority of VR1-immunopositive fibers are not colocalized with or apposed to c-kit positive interstitial cells of Cajal. Also electrophysiologically capsaicin had no effect on cultured interstitial cells of Cajal. It is concluded that VR1-immunoreactive intestinal nerves are mainly distributed in myenteric plexus of murine intestinal wall, and vanillod may be not directly related to interstitial cells of Cajal in regulation of intestinal motility.
Animals
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Capsaicin
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Ganglia
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Gastrointestinal Motility
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Immunohistochemistry
;
Interstitial Cells of Cajal
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Intestines
;
Mice*
;
Myenteric Plexus*
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Neurons, Afferent
;
Nodose Ganglion
;
Spinal Nerve Roots
9.Slow rise of intracellular Ca(2+) concentration in rat primary sensory neurons triggered by loureirin B.
Yi-Ning YANG ; Jue-Xu CHEN ; Xue-Yan PANG ; Susumu TERAKAWA ; Xu CHEN ; Yong-Hua JI ; Ke-Lan YONG
Acta Physiologica Sinica 2009;61(2):115-120
In the present study, the intracellular free calcium concentration ([Ca(2+)](i)) in acutely isolated rat dorsal root ganglia (DRG) neurons modulated by loureirin B, an active component of "dragon's blood" which is a kind of Chinese herbal medicine, was determined by the means of Fura-2 based microfluorimetry. It was found that loureirin B could evoke the elevation of [Ca(2+)](i) in a dose-dependent manner. However, the elevation of [Ca(2+)](i) evoked in the calcium free solution was much smaller than that in the standard external cell solution, suggesting that most change of [Ca(2+)](i) was generated by the influx of extracellular Ca(2+), not by the activities of intracellular organelles like Ca(2+) stores and mitochondria. In addition, the mixture of loureirin B and caffeine also induced [Ca(2+)](i) rise, but the peak of [Ca(2+)](i) rise induced by the mixture was significantly lower than that by caffeine alone, which means the triggering pathway and the targets of caffeine are probably involved in loureirin B-induced [Ca(2+)](i) rise. Moreover, compared to the transients induced by caffeine, KCl and capsaicin, the loureirin B-induced [Ca(2+)](i) rise is much slower and more stable. These results indicate that the capability of loureirin B of inducing the [Ca(2+)](i) rise is solid and unique.
Animals
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Caffeine
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pharmacology
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Calcium
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metabolism
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Ganglia, Spinal
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drug effects
;
metabolism
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Neurons, Afferent
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drug effects
;
metabolism
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Rats
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Resins, Plant
;
pharmacology
10.Recent evidence for activity-dependent initiation of sympathetic sprouting and neuropathic pain.
Jun-Ming ZHANG ; Judith A STRONG
Acta Physiologica Sinica 2008;60(5):617-627
Traumatic injury or inflammatory irritation of the peripheral nervous system often leads to persistent pathophysiological pain states. It has been well-documented that, after peripheral nerve injury or inflammation, functional and anatomical alterations sweep over the entire peripheral nervous system including the peripheral nerve endings, the injured or inflamed afferent fibers, the dorsal root ganglion (DRG), and the central afferent terminals in the spinal cord. Among all the changes, ectopic discharge or spontaneous activity of primary sensory neurons is of great clinical interest, as such discharges doubtless contribute to the development of pathological pain states such as neuropathic pain. Two key sources of abnormal spontaneous activity have been identified following peripheral nerve injury: the injured afferent fibers (neuroma) leading to the DRG, and the DRG somata. The purpose of this review is to provide a global account of the abnormal spontaneous activity in various animal models of pain. Particular attention is focused on the consequence of peripheral nerve injury and localized inflammation. Further, mechanisms involved in the generation of spontaneous activity are also reviewed; evidence of spontaneous activity in contributing to abnormal sympathetic sprouting in the axotomized DRG and to the initiation of neuropathic pain based on new findings from our research group are discussed. An improved understanding of the causes of spontaneous activity and the origins of neuropathic pain should facilitate the development of novel strategies for effective treatment of pathological pain.
Animals
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Axotomy
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Ganglia, Spinal
;
cytology
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Humans
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Neuralgia
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physiopathology
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Neurons, Afferent
;
cytology
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Peripheral Nerve Injuries
;
physiopathology
;
Spinal Cord
;
cytology