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1.
Neurosci Bull ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31933063

RESUMO

Acute pain is a common complication after injury of a peripheral nerve but the underlying mechanism is obscure. We established a model of acute neuropathic pain via pulling a pre-implanted suture loop to transect a peripheral nerve in awake rats. The tibial (both muscular and cutaneous), gastrocnemius-soleus (muscular only), and sural nerves (cutaneous only) were each transected. Transection of the tibial and gastrocnemius-soleus nerves, but not the sural nerve immediately evoked spontaneous pain and mechanical allodynia in the skin territories innervated by the adjacent intact nerves. Evans blue extravasation and cutaneous temperature of the intact skin territory were also significantly increased. In vivo electrophysiological recordings revealed that injury of a muscular nerve induced mechanical hypersensitivity and spontaneous activity in the nociceptive C-neurons in adjacent intact nerves. Our results indicate that injury of a muscular nerve, but not a cutaneous nerve, drives acute neuropathic pain.

2.
Neurosci Bull ; 36(1): 1-10, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31230211

RESUMO

Topical irritants such as capsaicin (CAP), peppermint oil (PO), and mustard oil (MO) are effective in relieving inflammatory muscle pain. We investigated the effects of topical irritants in a rat model of inflammatory muscle pain produced by injecting complete Freund's adjuvant (CFA) into the tibialis anterior muscle. CFA-induced mechanical hypersensitivity and the spontaneous activity of muscular nociceptive afferents, and decreased weight-bearing of the hindlimb were relieved by topical application of CAP, PO, or MO on the skin overlying the inflamed muscle. The effects of topical irritants were abolished when applied to the skin on the ipsilateral plantar region or on the contralateral leg, or when the relevant cutaneous nerve or dorsal root was transected. Our results demonstrated that topical irritants may alleviate inflammatory muscle pain via activating cutaneous nociceptors and subsequently inhibiting the abnormal activity of muscular nociceptive neurons.

3.
Sci Rep ; 9(1): 7651, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113988

RESUMO

Injury of peripheral nerves may quickly induce severe pain, but the mechanism remains obscure. We observed a rapid onset of spontaneous pain and evoked pain hypersensitivity after acute transection of the L5 spinal nerve (SNT) in awake rats. The outburst of pain was associated with a rapid development of spontaneous activities and hyperexcitability of nociceptive neurons in the adjacent uninjured L4 dorsal root ganglion (DRG), as revealed by both in vivo electrophysiological recording and high-throughput calcium imaging in vivo. Transection of the L4 dorsal root or intrathecal infusion of aminobutyrate aminotransferase inhibitor attenuated the spontaneous activity, suggesting that retrograde signals from the spinal cord may contribute to the sensitization of L4 DRG neurons after L5 SNT. Electrical stimulation of low-threshold afferents proximal to the axotomized L5 spinal nerve attenuated the spontaneous activities in L4 DRG and pain behavior. These findings suggest that peripheral axotomy may quickly induce hyperexcitability of uninjured nociceptors in the adjacent DRG that drives an outburst of pain.

4.
J Neuroinflammation ; 14(1): 70, 2017 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-28359290

RESUMO

BACKGROUND: MyD88 is the adaptor protein of MyD88-dependent signaling pathway of TLRs and IL-1 receptor and regulates innate immune response. However, it was not clear whether and how MyD88 and related signaling pathways in the dorsal root ganglion (DRG) and spinal dorsal horn (SDH) are involved in neuropathic pain. METHODS: Chronic constriction injury (CCI) was used to induce neuropathic pain in the rat. The expression of MyD88, TRIF, IBA1, and GFAP was detected with immunofluorescent staining and Western blot. The expression of interleukin-1 beta (IL-1ß), high mobility group box 1 (HMGB1), NF-κB-p65, phosphorylated NF-κB-p65, ERK, phosphorylated ERK, and tumor necrosis factor-alpha (TNF-α) was detected with Western blot. Pain-related behavioral effects of MyD88 homodimerization inhibitory peptide (MIP) were accessed up to 3 weeks after intrathecal administration. RESULTS: Peripheral nerve injury significantly increased the protein level of MyD88 in the DRG and SDH, but had no effect on TRIF. MyD88 was found partly distributed in the nociceptive neurons in the DRGs and the astrocytes and microglia in the SDH. HMGB1 and IL-1ß were also found upregulated in nociceptive pathways of CCI rats. Intrathecal application of MIP significantly alleviated mechanical and thermal hyperalgesia in the CCI rats and also reversed CCI-induced upregulation of MyD88 in both DRG and SDH. Further investigation revealed that suppression of MyD88 protein reduced the release of TNF-α and glial activation in the SDH in the CCI rats. CONCLUSIONS: MyD88-dependent TIR pathway in the DRG and SDH may play a role in CCI-induced neuropathic pain. MyD88 might serve as a potential therapeutic target for neuropathic pain.


Assuntos
Gânglios Espinais/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Neuralgia/metabolismo , Traumatismos dos Nervos Periféricos/metabolismo , Corno Dorsal da Medula Espinal/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia
5.
Brain Behav Immun ; 62: 351-361, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28263785

RESUMO

Antigen-specific immune diseases such as rheumatoid arthritis are often accompanied by pain and hyperalgesia. Our previous studies have demonstrated that Fc-gamma-receptor type I (FcγRI) is expressed in a subpopulation of rat dorsal root ganglion (DRG) neurons and can be directly activated by IgG immune complex (IgG-IC). In this study we investigated whether neuronal FcγRI contributes to antigen-specific pain in the naïve and rheumatoid arthritis model rats. In vitro calcium imaging and whole-cell patch clamp recordings in dissociated DRG neurons revealed that only the small-, but not medium- or large-sized DRG neurons responded to IgG-IC. Accordingly, in vivo electrophysiological recordings showed that intradermal injection of IgG-IC into the peripheral receptive field could sensitize only the C- (but not A-) type sensory neurons and evoke action potential discharges. Pain-related behavioral tests showed that intradermal injection of IgG-IC dose-dependently produced mechanical and thermal hyperalgesia in the hindpaw of rats. These behavioral effects could be alleviated by localized administration of non-specific IgG or an FcγRI antibody, but not by mast cell stabilizer or histamine antagonist. In a rat model of antigen-induced arthritis (AIA) produced by methylated bovine serum albumin, FcγRI were found upregulated exclusively in the small-sized DRG neurons. In vitro calcium imaging revealed that significantly more small-sized DRG neurons responded to IgG-IC in the AIA rats, although there was no significant difference between the AIA and control rats in the magnitude of calcium changes in the DRG neurons. Moreover, in vivo electrophysiological recordings showed that C-nociceptive neurons in the AIA rats exhibited a greater incidence of action potential discharges and stronger responses to mechanical stimuli after IgG-IC was injected to the receptive fields. These results suggest that FcγRI expressed in the peripheral nociceptors might be directly activated by IgG-IC and contribute to antigen-specific pain in pathological conditions.


Assuntos
Complexo Antígeno-Anticorpo , Gânglios Espinais/metabolismo , Nociceptores/metabolismo , Dor/metabolismo , Receptores de IgG/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Feminino , Gânglios Espinais/efeitos dos fármacos , Nociceptores/efeitos dos fármacos , Dor/induzido quimicamente , Medição da Dor , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley
6.
Brain Behav Immun ; 61: 165-175, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27865948

RESUMO

Pruritus is the major symptom of ocular allergy but currently available treatments are often ineffective. Previous studies demonstrated that subpopulations of primary sensory neurons express Fc receptors and may contribute to antigen-specific pain. We investigated the role of neuronal Fc-epsilon Receptor I (FcεRI) in allergic ocular pruritus. Ovalbumin (OVA) was used as allergen together with alum adjuvant (OVA+alum) to produce a mouse model of ocular allergy with a significant elevation in the serum levels of both antigen-specific IgE and IgG. Mice sensitized by OVA without alum only induced elevation of serum IgG but not IgE. Scratching behavior toward the eyes with the hindlimb was used as an indicator of ocular itch. Topical OVA challenging to the eye dose-dependently induced scratching toward the eye in the OVA+alum sensitized mice, but not those sensitized by OVA only. The antigen-induced scratching was largely abolished by topical application of the blocking antibody to FcεRIα, but was only partially alleviated by pretreatment of mast cell stabilizer or histamine I receptor antagonist. The expression of FcεRI was detected in subpopulations of trigeminal ganglion (TG) neurons including those expressing pruriceptive markers and innervating the conjunctiva in the naïve mice. Moreover, FcεRI was found significantly upregulated in small-sized TG neurons in the OVA+alum sensitized mice. In acutely dissociated TG neurons, IgE-immune complex (IC), but not the antibody or antigen alone, induced intracellular calcium increase. The neuronal responses to IgE-IC could be specifically blocked by pre-application of a siRNA for FcεRIα. Our results indicate that FcεRI expressed on peripheral nociceptive neurons in the TG may be directly activated by IgE-IC and contribute to allergic ocular pruritus. This study may suggest a novel mechanism for the development of pathological itch in allergic diseases.


Assuntos
Oftalmopatias/metabolismo , Hipersensibilidade/metabolismo , Neurônios/metabolismo , Prurido/metabolismo , Receptores de IgE/metabolismo , Compostos de Alúmen , Animais , Modelos Animais de Doenças , Oftalmopatias/imunologia , Hipersensibilidade/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neurônios/imunologia , Ovalbumina , Prurido/imunologia
8.
Adv Exp Med Biol ; 904: 33-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26900061

RESUMO

To understand the mechanisms of neuropathic pain caused by demyelination, a rapid-onset, completed but reversible demyelination of peripheral A-fibers and neuropathic pain behaviors in adult rats by single injection of cobra venom into the sciatic nerve, was created. Microfilament recording revealed that cobra venom selectively blocked A-fibers, but not C-fibers. Selective blockade of A-fibers may result from A-fiber demyelination at the site of venom injection as demonstrated by microscope examination. Neuropathic pain behaviors including inflammatory response appeared almost immediately after venom injection and lasted about 3 weeks. Electrophysiological studies indicated that venom injection induced loss of conduction in A-fibers, increased sensitivity of C-polymodal nociceptors to innocuous stimuli, and triggered spontaneous activity from peripheral and central terminals of C-fiber nociceptors. Neurogenic inflammatory responses were also observed in the affected skin via Evans blue extravasation experiments. Both antidromic C-fiber spontaneous activity and neurogenic inflammation were substantially decreased by continuous A-fiber threshold electric stimuli applied proximally to the venom injection site. The data suggest that normal activity of peripheral A-fibers may produce inhibitory modulation of C-polymodal nociceptors. Removal of inhibition to C-fiber polymodal nociceptors following demyelination of A-fibers may result in pain and neurogenic inflammation in the affected receptive field.


Assuntos
Doenças Desmielinizantes/fisiopatologia , Fibras Nervosas Mielinizadas/fisiologia , Fibras Nervosas Amielínicas/fisiologia , Neuralgia/fisiopatologia , Nociceptividade/fisiologia , Nervo Isquiático/fisiopatologia , Animais , Venenos Elapídicos/toxicidade , Azul Evans , Extravasamento de Materiais Terapêuticos e Diagnósticos , Hiperalgesia/induzido quimicamente , Hiperalgesia/fisiopatologia , Inflamação , Condução Nervosa , Neuralgia/induzido quimicamente , Neuralgia/patologia , Nociceptividade/efeitos dos fármacos , Ratos , Nervo Isquiático/efeitos dos fármacos
9.
Biomed Eng Online ; 14: 118, 2015 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-26689592

RESUMO

BACKGROUND: Implantation of deep brain stimulation (DBS) electrodes is a landmark therapy for movement disorders and some mental conditions. Compared to conventional platinum-iridium (Pt-Ir) electrodes, carbon nanotube yarns (CNTY) electrodes have improved stability and interface characteristics with less distortion during high field strength MRI. Sprague-Dawley rat models were used to examine thein vivo histological and imaging properties of biocompatible CNTY throughout the subacute period. METHODS: Sprague-Dawley rats received CNTY (n = 16) or Pt-Ir control (n = 16) electrodes. Behavioral markers, body weight, and survival were recorded. Comparative histology (HE, NeuN, CD68, and GFAP) was performed at 1, 6, and 12 weeks post-implantation; 3.0T MRI was performed at 1 and 12 weeks. RESULTS: Of 32 rats, 30 (15 per group) survived implantation without reduced activity, paralysis, or incapacity to feed. Following implantation, progressive decreases in macrophage activation and neuron-depleted margins surrounding electrodes were observed in both groups. Inflammatory marker expression (CD68) was significantly lower in rats with implanted CNTY electrodes compared to controls at all time points. CNTY electrodes also caused less inflammation and shallower depths of macrophage penetration and neural disruption relative to the interface. Artifacts and distortion were observed on MRI of Pt-Ir but not CNTY electrodes. CONCLUSIONS: CNTY electrodes exhibited reduced inflammatory margins compared to Pt-Ir electrodes throughout the subacute period, indicating reduced initial trauma, better overall biocompatibility, and reduced fibrous tissue formation. Coupled with less MRI distortion, CNTY electrodes may be useful alternatives when there is a need to monitor electrode placement by MRI.


Assuntos
Eletrodos Implantados/efeitos adversos , Imagem por Ressonância Magnética , Teste de Materiais , Nanotubos de Carbono/efeitos adversos , Animais , Comportamento Animal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Encéfalo/citologia , Ativação de Macrófagos/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
10.
Pain Med ; 14(9): 1381-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23870161

RESUMO

OBJECTIVE: To investigate the possible mechanisms of topical analgesics in relieving pain in an animal model of muscular inflammation. METHODS: Adult Sprague-Dawley rats of both sexes were injected with complete Freund's adjuvant to induce inflammation in the anterior tibialis muscle of left hindlimb. One of two types of topical analgesics: Xiaotong Tiegao (XTT), a Tibetan herb compound, or Capzasin (CAP), a cream containing 0.1% capsaicin, was applied to the skin over the inflamed anterior tibialis muscle. The following experiments were performed: pain behavioral tests, evaluation of plasma extravasation in the affected limb, and electrophysiological recordings of afferent nerve fibers. RESULTS: The behavioral experiments demonstrated that applications of either type of topical analgesic to the skin over the inflamed muscle significantly reduced muscular inflammatory pain, as indicated by the increased weight bearing capacity on the affected hindlimb (with latencies of 10 minutes for XTT and 1-2 hours for CAP). Meanwhile, both analgesics caused plasma extravasation in the affected skin. Electrophysiological recordings from the afferent fibers in the related cutaneous nerve indicated that topical analgesics selectively activated C-fibers, but not A-fibers innervating the same region of receptive field. The latency and duration of C-fiber activation was similar to those of the reduction of muscular inflammatory pain. On the contrary, topical analgesics substantially decreased C-fiber afferent spontaneous firing in the nerve innervating the inflamed muscle. Moreover, denervation of the affected skin blocked the analgesic effects of both topical analgesics in muscular inflammatory pain. CONCLUSION: This study suggests that topical analgesics may reduce the nociceptive input from inflamed muscles via a reflex mechanism by activating the cutaneous nociceptive afferents.


Assuntos
Analgésicos/administração & dosagem , Miosite/tratamento farmacológico , Fibras Nervosas Amielínicas/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/inervação , Potenciais de Ação/efeitos dos fármacos , Administração Cutânea , Vias Aferentes/efeitos dos fármacos , Animais , Capsaicina/administração & dosagem , Modelos Animais de Doenças , Eletrofisiologia , Feminino , Masculino , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Tibet
11.
Zhen Ci Yan Jiu ; 38(6): 447-52, 458, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24579358

RESUMO

OBJECTIVE: Previous studies indicated a close involvement of reflex activities of motoneurons in the spinal cord in the mechanism of meridian phenomena. The present study was designed to investigate the dendrite projections of meridian-related motoneurons among the motoneurons and sympathetic preganglionic neurons in the spinal cord. METHODS: A total of 41 Sprague-Dawley rats were used in the present study. Cholera toxin B-subunit conjugated horseradish peroxidase (CB-HRP) containing 1.0% HRP was respectively injected to acupoint "Chengman" (ST 20), "Liangmen" (ST 21), "Guanmen" (ST 22), "Taiyi" (ST 23), "Huaroumen" (ST 24), "Tianshu" (ST 25) and "Wailing" (ST 26) of the Stomach Meridian, and "Ganshu" (BL 18), "Danshu" (BL 19), "Pishu" (BL 20), "Weishu" (BL 21) and "Sanjiaoshu" (BL 22) of the Bladder Meridian, and "Daimai" (GB 26), "Wushu" (GB 27), "Weidao" (GB 28), "Juliao" (GB 29), "Huantiao" (GB 30), "Fengshi" (GB 31), "Zhongdu" (GB 32), "Xiyangguan" (GB 33) and "Yanglingquan" (GB 34) of the Gallbladder Meridian (for labeling preganglionic neurons), and the celiac ganglion and superior mesenteric ganglion for labeling sympathetic preganglionic neurons. Three days after injection, the animals anesthetized were transcardia-cally perfused with 1.5% paraformaldehyde, the spinal cord was removed to be fixed routinely and then cut into sections for observing the labeled cells under microscope. RESULTS: In the ipsilateral ventral horn of the spinal cord, the motoneurons retrogradely labeled by CB-HRP formed dendritic projections oriented only to those motoneurons innervating the same meridian. In the longitudinal sections of spinal cord, the labeled motoneurons formed a bead-like column with a prominent network of longitudinal dendrites connecting the motoneurons innervating acupoints from the same meridian. In the transverse sections of spinal cord, two groups of dendrites from the labeled motoneurons projected to the identified sympathetic preganglionic regions: one group extended dorsolateraly to the intermediolateral gray, another group extended intermediolateraly toward the central canal. In rats with injection of CB-HRP into both acupoint regions and ipsilateral celiac ganglion, the dendrites originated from the labeled motoneurons projected directly to the labeled sympathetic preganglionic neurons. CONCLUSION: Each of the ST, BL and GB meridians is innervated by a specific group of motoneurons in the spinal cord. The motoneurons form a column with distinct border in the ventral horn of spinal cord, and the dendritic projections from the motoneurons oriented only to those innervating the same meridian. The dendrites from the meridian-related motoneurons can specifically project to the sympathetic preganglionic neurons at the thoracolumbar level.


Assuntos
Dendritos/fisiologia , Gânglios Simpáticos/citologia , Meridianos , Neurônios Motores/citologia , Medula Espinal/citologia , Pontos de Acupuntura , Animais , Feminino , Cistos Glanglionares , Humanos , Masculino , Ratos , Ratos Sprague-Dawley
12.
Anesth Analg ; 113(3): 652-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21778333

RESUMO

BACKGROUND: Understanding the mechanism of trigeminal neuralgia may be elucidated by developing laboratory animal models that closely mimic the features of this specific type of neuropathic pain. We have developed an experimental animal model for trigeminal neuralgia using a technique of injecting cobra venom into the infraorbital nerve (ION) trunk. METHODS: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the ION trunk. Mechanical stimuli were applied to the ION territory in consecutive days after surgery. Mechanical thresholds were measured over a 90-day period on the bilateral facial region. Vascular permeability in the ION territory was measured using Evans blue dye. RESULTS: The cobra venom-treated rats developed mechanical allodynia 3 days after surgery that lasted for 60 days postoperatively at the ipsilateral side. The mechanical thresholds of the contralateral ION territory also showed a profound decrease but were sustained for only approximately 30 days. There was no change of mechanical thresholds in the control groups. The extravasation of Evans blue increased significantly in the skin after administration of cobra venom to the ION compared with control rats (P < 0.05). CONCLUSION: The cobra venom model may provide a reasonable model for investigating the mechanism of trigeminal neuropathic pain.


Assuntos
Modelos Animais de Doenças , Venenos Elapídicos , Hiperalgesia/induzido quimicamente , Órbita/inervação , Nervo Trigêmeo/fisiopatologia , Neuralgia do Trigêmeo/induzido quimicamente , Animais , Permeabilidade Capilar , Corantes/metabolismo , Azul Evans/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatologia , Masculino , Órbita/irrigação sanguínea , Medição da Dor , Limiar da Dor , Ratos , Ratos Sprague-Dawley , Pele/irrigação sanguínea , Fatores de Tempo , Nervo Trigêmeo/metabolismo , Neuralgia do Trigêmeo/metabolismo , Neuralgia do Trigêmeo/fisiopatologia
13.
Zhen Ci Yan Jiu ; 34(1): 36-42, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19526806

RESUMO

OBJECTIVE: To study the innervating character of tissues around the acupoints and along the meridian course and to analyze the reflex activity correlation between acupuncture points in a given meridian in the rat. METHODS: Forty Wistar and 15 SD rats were used in this study. Electrical activities of microfilaments of the afferent nerves (deep tibial nerve, peroneal nerve and the lateral cutaneous nerve of the leg) were observed for identifying their receptive field and the type of nerve fibers. Nerve stem-antidromic stimulation induced Evan's blue extravasation method was employed to compare the difference of the nerve ending distribution in the acupoint area and non-acupoint area. The reflex activities evoked by electric stimulation of the acupoint were used to analyze the interrelation between acupoint and meridian. RESULTS: Findings showed that a great majority of the afferent nerve endings supplying the tibialis anterior/rectus femoris muscle and the foot skin distributed in an uneven pattern in the sites being in accord with acupoints or with the orbit of meridians. Antidromic stimulation of C-fibers in the deep tibial nerve evoked extravasation of Evan's blue from the plasma into the interstitial fluid, blue foci appeared at the acupoints of the Stomach Meridian and along the orbit of the Stomach Meridian. The special distribution of the afferent nerve endings in the acupoint was also associated with the special reflex activity originating from the acupoints of the muscle group of a given meridian. CONCLUSION: The acupoint is an excitable muscle/skin-nerve complex with greatest concentration of nerve endings. The meridian consists of acupoints that possess a close interaction in physiological reflex activities.


Assuntos
Pontos de Acupuntura , Neurônios Aferentes/fisiologia , Ratos Wistar , Reflexo , Nervo Isquiático/fisiologia , Animais , Estimulação Elétrica , Feminino , Masculino , Meridianos , Ratos
14.
Brain Res ; 1139: 201-9, 2007 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-17291461

RESUMO

Subthreshold membrane potential oscillations (SMPO) in the injured dorsal root ganglion (DRG) neurons are involved in the generation of spontaneous activity, which can directly evoke neuropathic pain. Nerve injury usually triggers the synthesis of large quantities of membrane protein in nerve injured DRG neurons. Membrane proteins are glycosylated by addition of sugars, especially negatively charged sialic acid residues, which may depolarize the resting membrane potential (Vm), open voltage-gated channels in injured neurons, and cause spontaneous activity. In the present study, we aimed to determine if increased negative charge on the cell surface, carried by the sialic acid residues, could contribute to the generation of SMPO in injured DRG neurons. Intracellular recording was performed in DRG neurons following chronic constrictive injury (CCI) of the sciatic nerve. Results indicated that both A- and C-type injured DRG neurons exhibited a higher incidence of SMPO and more depolarized Vm than those of the control neurons. Ca(2+), Mg(2+), Mn(2+), or poly-lysine, a positively charged organic compound, when topically applied to the DRG, not only reduced SMPO but also caused a rapid hyperpolarizing shift in Vm. Topical application of neuraminidase to selectively remove sialic acid residues on the extracellular membrane normalized the depolarized Vm and inhibited both spontaneous and evoked SMPO. However, application of Ca(2+), Mg(2+), Mn(2+) or neuraminidase had no effect on excitability and Vm in normal neurons. The results demonstrated that the increase in negatively charged sialic acid residues on the extracellular membrane of neuronal somata is a critical factor in the generation of SMPO and hyperexcitability in injured sensory neurons.


Assuntos
Gânglios Espinais/fisiologia , Potenciais da Membrana/fisiologia , Ácido N-Acetilneuramínico/metabolismo , Degeneração Neural/fisiopatologia , Neurônios Aferentes/fisiologia , Análise de Variância , Animais , Gânglios Espinais/citologia , Glicosilação , Proteínas de Membrana/metabolismo , Compressão Nervosa/efeitos adversos , Degeneração Neural/complicações , Oscilometria , Dor/etiologia , Dor/fisiopatologia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/lesões , Nervo Isquiático/metabolismo , Nervo Isquiático/fisiopatologia
15.
Brain Res ; 1055(1-2): 103-10, 2005 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-16083864

RESUMO

A spinal cord injury (SCI) was produced in adult rats by complete spinal cord transection at L6-S1. Neuropathic pain behaviors similar to the chronic central pain (CCP) syndrome in human, such as thermal hyperalgesia, mechanical allodynia and autotomy, were present in these rats after spinal cord injury. Meanwhile, wide dynamic range (WDR) neurons recorded in the spinal dorsal horn rostral to the lesion responded as high frequency of spontaneous activities, long duration of after-discharges to noxious electrical stimuli and an augmented wind-up to 0.5 Hz stimuli. By using bupivacaine powder, a sodium channel blocker, at the locus of transection immediate after nerve injury, the chronic pain behaviors were prevented; the hyperexcitability of WDR neurons was also substantially reduced. It is suggested that spinal cord transection induces the CCP syndromes, which may be evoked and maintained by the hyperexcitability in WDR neurons rostrally. Reducing the neuronal activity at the site of lesion following injury may prevent the development of CCP after SCI.


Assuntos
Hiperalgesia/fisiopatologia , Células do Corno Posterior/fisiopatologia , Traumatismos da Medula Espinal/patologia , Animais , Comportamento Animal , Estimulação Elétrica/efeitos adversos , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/fisiologia , Potenciais Evocados/efeitos da radiação , Feminino , Temperatura Alta/efeitos adversos , Hiperalgesia/etiologia , Medição da Dor , Estimulação Física , Ratos , Ratos Sprague-Dawley , Tempo de Reação/fisiologia , Traumatismos da Medula Espinal/fisiopatologia
16.
Brain Res ; 1026(2): 185-93, 2004 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-15488480

RESUMO

Axonal injury of the dorsal root ganglion (DRG) neurons may alter the synthesis of certain membrane proteins that are responsible for the development of abnormal hyperexcitability. The external domains of most of these membrane proteins are sialylated. Because sialic acid carries heavy negative charges, the increase of sialylated proteins may increase neurons' negative surface charges, which will have predictable effects on the voltage-gated channels, and affect the excitability of injured neurons. Using intracellular electrophysiological recording, we demonstrated that following chronic constriction injury (CCI) of the sciatic nerve, Aalpha/beta DRG neurons become hyperexcitable, as indicated by a more depolarized resting membrane potential (Vm) and a lowered threshold current (TIC). More interestingly, the excitability of injured DRG neurons was reduced substantially when the extracellular sialic acid was removed by pretreatment with neuraminidase. The Vm was less depolarized and the TIC increased robustly as compared to the CCI neurons without neuraminidase treatment. However, desialylation of normal, intact neurons had no significant effect on the Vm and less effect on the TIC. Our results suggest that the hyperexcitability of injured sensory neurons may be associated with increased negatively charged sialic acid residues on the surface of the neuronal somata.


Assuntos
Gânglios Espinais/patologia , Ácido N-Acetilneuramínico/farmacologia , Neurônios/efeitos dos fármacos , Doenças do Sistema Nervoso Periférico/patologia , Animais , Constrição , Estimulação Elétrica/métodos , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/efeitos da radiação , Condução Nervosa/efeitos dos fármacos , Condução Nervosa/efeitos da radiação , Neuraminidase/farmacologia , Neurônios/fisiologia , Técnicas de Patch-Clamp/métodos , Ratos
18.
Brain Res ; 1012(1-2): 154-9, 2004 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-15158172

RESUMO

As part of our ongoing investigation into the neurological mechanisms of acupuncture, we have tried to correlate the distribution of afferent nerve endings with acupuncture points (AP) in the rat hind limbs. In vivo extracellular microfilament recordings of Aalpha/Abeta/Adelta fibers were taken from peripheral nerves to search for units with nerve endings or receptive fields (RF) in the skin or the muscles. The location of the RFs for each identified unit was marked on scaled diagrams of the hind limb. Noxious antidromic stimulation-induced Evans blue extravasation was used to map the RFs of C-fibers in the skin or muscles. Results indicate that, for both A- and C-fibers, the distribution of RFs was closely associated with the APs. In the skin, the RFs concentrate either at the sites of APs or along the orbit of meridian channels. Similarly, the majority of sarcous sensory receptors are located at the APs in the muscle. Results from our studies strongly suggest that APs in humans may be excitable muscle/skin-nerve complexes with high density of nerve endings.


Assuntos
Pontos de Acupuntura , Músculo Esquelético/inervação , Terminações Nervosas/fisiologia , Pele/inervação , Animais , Feminino , Humanos , Masculino , Mecanorreceptores/fisiologia , Nervos Periféricos/fisiologia , Ratos , Ratos Sprague-Dawley
19.
Neurosci Lett ; 346(1-2): 65-8, 2003 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-12850549

RESUMO

Ectopic spontaneous discharges (ESD) of teased myelinated fibers were recorded from the sciatic nerve proximal to the site of 'chronic constriction nerve injury' in the rat. Ca(2+), Mg(2+), Mn(2+), Ni(2+), La(3+) and some positively charged organic compounds (hexamethonium and poly-lysine) when applied topically to the injured site abolished or significantly reduced the rate of ESD. After enzymatic removal of sialic acid by neuraminidase (2 units/ml), the ESD was silenced in 11, reduced in four and unchanged in four of 19 fibers. However, divalent cations failed to depress the reappeared ESD evoked by 4-aminopyridine in the desialylated silenced fibers. Moreover, the mean incidence of ESD was significantly reduced after neuraminidase treatment. These results indicate that an increase in negative charges on the external membrane surface of injured neuron caused by sialylation is a key factor in ESD generation.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Ácido N-Acetilneuramínico/farmacologia , Dor/fisiopatologia , Doenças do Sistema Nervoso Periférico/fisiopatologia , Neuropatia Ciática/fisiopatologia , Potenciais de Ação/fisiologia , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley
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