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1.
Neuromodulation ; 22(2): 172-178, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30221804

RESUMO

OBJECTIVES: Clinical high-frequency spinal cord stimulation (hfSCS) (>250 Hz) applied at subperception amplitudes reduces leg and low back pain. This study investigates, via labeling for c-fos-a marker of neural activation, whether 500 Hz hfSCS applied at amplitudes above and below the dorsal column (DC) compound action potential (CAP) threshold excites dorsal horn neurons. MATERIALS AND METHODS: DC CAP thresholds in rats were determined by applying single biphasic pulses of SCS to T12 -T13 segments using pulse widths of 40 or 200 µsec via a ball electrode placed over the left DC and increasing amplitude until a short latency CAP was observed on the L5 DC and sciatic nerve. The result of this comparison allowed us to substitute sciatic nerve CAP for DC CAP. SCS at T12 -T13 was applied continuously for two hours using: sham or hfSCS at 500 Hz SCS, 40 µsec pulse width, and 50, 70, 90, or 140% CAP threshold. Spinal cord slices from T11 -L1 were immunolabeled for c-fos, and the number of c-fos-positive cells was quantified. RESULTS: 500 Hz hfSCS applied at 90 and 140% CAP threshold produced substantial (≥6 c-fos + neurons on average per slice per segment) c-fos expression in more segments between T11 and L1 than did sham stimulation (p < 0.025, 90% CAP; p < 0.001, 140% CAP, Fisher's Exact Tests) and resulted in more c-fos-positive neurons on average per slice per segment ipsilateral to than contralateral to the SCS electrode at 70, 90, and 140% CAP threshold (p < 0.01, Wilcoxon Signed Rank Tests). CONCLUSIONS: The finding of enhanced c-fos expression in the ipsilateral superficial dorsal horn provides evidence for activation/modulation of neuronal circuitry associated with subperception hfSCS.


Assuntos
Potenciais de Ação/fisiologia , Fenômenos Biofísicos/fisiologia , Modelos Animais , Células do Corno Posterior/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Estimulação da Medula Espinal/métodos , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/fisiologia , Limiar Sensorial/fisiologia
2.
Neuromodulation ; 21(5): 440-447, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29164752

RESUMO

OBJECTIVES: Spinal cord stimulation (SCS) at both conventional and higher frequencies may effectively reduce pain, but optimal parameters need to be established. This study investigated how SCS at different frequencies and pulse widths acutely modulates nociceptive activity of wide dynamic range (WDR) and high threshold (HT) dorsal horn neurons in rats at a stimulus amplitude that influences both local circuits and dorsal column fibers. MATERIALS AND METHODS: L2 -L3 and L6 -S2 spinal segments were exposed for SCS and spinal neuronal recordings, respectively. Responses to pinch of a hindpaw were recorded before and after SCS (40 or 200 µsec pulse width at 50, 500, 1 kHz and 10 kHz, amplitude: 90% of motor threshold) for 5 or 20 min. Pinch responses were tested within 30 s after SCS ceased (first pinch) and at ∼4 min intervals until response recovery. RESULTS: 1) SCS for 5 min suppressed averaged first pinch responses, except for 40 µsec/50 Hz. 2) Only SCS with 40 µs/1 kHz suppressed more spinal neurons than 200 µsec/50 Hz. 3) All SCS parameters at 5 min increased pinch responses for a small population of cells, with the incidence being greater for WDR than for HT neurons. 4) SCS at 1 kHz (40 or 200 µsec) for 20 min reduced the response to the second pinch as compared with baseline responses. In addition, no neurons exhibited increased pinch responses. CONCLUSIONS: Compared with a typical low frequency SCS (200 µs/50 Hz) or high-frequency SCS at 10 kHz, at an amplitude designed to influence both local spinal circuits and dorsal column fiber tracts, 1 kHz SCS suppressed nociceptive responses of more spinal neurons and/or demonstrated longer persisting suppressive effects. SCS at 1 kHz surpassed both low-frequency (50 Hz) and high-frequency (10 kHz) SCS application in this normal animal model.


Assuntos
Potenciais de Ação/fisiologia , Neurônios/fisiologia , Estimulação Física/efeitos adversos , Estimulação da Medula Espinal/métodos , Medula Espinal/citologia , Análise de Variância , Animais , Biofísica , Modelos Animais de Doenças , Masculino , Dor/etiologia , Dor/patologia , Dor/fisiopatologia , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
3.
Neuromodulation ; 17(2): 143-51, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24655042

RESUMO

OBJECTIVES: Spinal cord stimulation (SCS) using bursts of pulses suppressed neuropathic pain as well or better than tonic stimulation and limited the incidences of parasthesias. The present translational study explored possible differences in mechanisms of burst and tonic SCS on nociceptive spinal networks and/or the gracile nucleus supraspinal relay. MATERIALS AND METHODS: Visceromotor reflexes (VMRs, a nociceptive response) or extracellular activity of either L6-S2 spinal neurons or gracile nucleus neurons were recorded during noxious somatic stimulation (pinching) and visceral stimulation (colorectal distension [CRD]) in anesthetized rats. A stimulating (unipolar, ball) electrode at L2-L3 delivered 40 Hz burst or tonic SCS at different intensities relative to motor threshold (MT). RESULTS: Average MTs for burst SCS were significantly lower than for tonic SCS. Burst SCS reduced the VMR more than tonic SCS. After high-intensity SCS (90% MT), spinal neuronal responses to CRD and pinch were reduced similarly for burst and tonic SCS. At low-intensity SCS (60% MT), only burst SCS significantly decreased the nociceptive somatic response. Tonic but not burst SCS significantly increased spontaneous activity of neurons in the gracile nucleus. CONCLUSION: Based on the clinically relevant burst versus tonic parameters used in this study, burst SCS is more efficacious than tonic SCS in attenuating visceral nociception. Burst and tonic SCS also suppress lumbosacral neuronal responses to noxious somatic and visceral stimuli; however, burst SCS has a greater inhibitory effect on the neuronal response to noxious somatic stimuli than to noxious visceral stimuli. Reduced or abolished paresthesia in patients may be due in part to burst SCS not increasing spontaneous activity of neurons in the gracile nucleus.


Assuntos
Modelos Animais , Medição da Dor/métodos , Estimulação da Medula Espinal/métodos , Nervos Espinhais/fisiologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Dor Visceral/fisiopatologia
4.
Neuromodulation ; 15(2): 132-42; discussion 143, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22364336

RESUMO

OBJECTIVES: This study compares the effects of constant current (CC) and constant voltage (CV) spinal cord stimulation (SCS) at various frequencies and intensities on standard nociceptive measurements in rats, the visceromotor reflex (VMR) and neuronal activity, during noxious visceral and somatic stimuli. MATERIALS AND METHODS: Abdominal muscle electromyographic activity changes were measured to indicate VMR, and extracellular activity of L6-S2 spinal neurons was recorded during somatic (pinching) and noxious visceral stimulation (colorectal distension [CRD], 60 mmHg) in anesthetized rats. A stimulating (unipolar ball) electrode at L2-L3 delivered CC- or CV-SCS at varied frequencies and intensities. RESULTS: CC-SCS reduced VMR evoked by CRD significantly more than CV-SCS (p < 0.05). For neuronal activity, high-frequency CC-SCS (40 and 100 Hz) and CV-SCS (100 Hz) effectively reduced intraspinal somatic nociceptive transmission more than low-frequency SCS (2 Hz). No significant differences were observed between the effects of CC- and CV-SCS on spontaneous activity and nociceptive responses of spinal neurons to noxious CRD following short- (five to ten minutes) or long-term (20-30 min) SCS. CONCLUSIONS: Although high-frequency CC- and CV-SCS may be more useful for the management of somatic pain, CC-SCS may be more effective for treating complex pain systems like visceral hypersensitivity.


Assuntos
Terapia por Estimulação Elétrica/métodos , Dor Nociceptiva/terapia , Nociceptores/fisiologia , Medula Espinal/fisiologia , Potenciais de Ação/fisiologia , Animais , Colo/inervação , Modelos Animais de Doenças , Eletromiografia , Laminectomia , Masculino , Inibição Neural/fisiologia , Neurônios/fisiologia , Dor Nociceptiva/etiologia , Estimulação Física/efeitos adversos , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Fibras Aferentes Viscerais
5.
Auton Neurosci ; 165(2): 168-77, 2011 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-21862419

RESUMO

The aim of the present study was to examine spinal processing of cardiac and somatic nociceptive input in rats with STZ-induced diabetes. Type 1 diabetes was induced with streptozotocin (50mg/kg) in 14 male Sprague-Dawley rats and citrate buffer was injected in 14 control rats. After 4-11 weeks, the rats were anesthetized with pentobarbital, ventilated and paralyzed. A laminectomy enabled extracellular recording of T(3) spinal cord neuronal activity. Intrapericardial administration of a mixture of algogenic chemicals (bradykinin, serotonin, prostaglandin E(2) (all at 10(-5)M), and adenosine (10(-3)M)) was applied to activate nociceptors of cardiac afferent nerve endings. Furthermore, somatic receptive properties were examined by applying innocuous (brush and light pressure) and noxious (pinch) cutaneous mechanical stimuli. Diabetes-induced increases in spontaneous activity were observed in subsets of neurons exhibiting long-lasting excitatory responses to administration of the algogenic mixture. Algogenic chemicals altered activity of a larger proportion of neurons from diabetic animals (73/111) than control animals (55/115, P<0.05). Some subtypes of neurons exhibiting long-lasting excitatory responses, elicited prolonged duration and others, had a shortened latency. Some neurons exhibiting short-lasting excitatory responses in diabetic animals elicited a shorter latency and some a decreased excitatory change. The size of the somatic receptive field was increased for cardiosomatic neurons from diabetic animals. Cutaneous somatic mechanical stimulation caused spinal neurons to respond with a mixture of hyper- and hypoexcitability. In conclusion, diabetes induced changes in the spinal processing of cardiac input and these might contribute to cardiovascular autonomic neuropathy in patients with diabetes.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Coração/inervação , Neurônios Aferentes/fisiologia , Medula Espinal/fisiopatologia , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Vértebras Torácicas
6.
Brain Res ; 1413: 24-31, 2011 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-21839425

RESUMO

Sex differences in the characteristics of cardiac pain have been reported from clinical studies. For example, women experience chest pain less frequently than men. Women describe their chest pain as sharp and stabbing, while men have chest pain that is felt as a pressure or heaviness. Pain is also referred to the back more often in women than men. The mechanisms underlying sex differences in cardiac pain are unknown. One possible mechanism for the observed differences could be related to plasma estradiol. This study investigated the actions of estradiol on the activity of T(3) spinal neurons that process cardiosomatic information in male and female rats. Extracellular potentials of T(3) spinal neurons were recorded in response to mechanical somatic stimulation and noxious chemical cardiac stimulation in pentobarbital-anesthetized male and proestrous female rats. Fifty one percent and fifty percent of neurons responded to intrapericardial algogenic chemicals (0.2 ml) in male and female rats, respectively. Somatic fields were located by applying brush, pressure, and pinch to the upper body. Of those neurons receiving cardiac input, 54% in female and 55% in male rats also received somatic input. In both male and female rats, 81% of neurons responding to somatic stimuli had somatic fields located on the side of the upper body, while 19% of neurons had somatic fields located on the chest. These results indicate there are no significant differences in the responses of T(3) spinal neurons to cardiosomatic stimulation between male and proestrous female rats, despite differences in estradiol levels.


Assuntos
Dor no Peito/fisiopatologia , Sistema de Condução Cardíaco/fisiopatologia , Nociceptividade/fisiologia , Proestro/fisiologia , Caracteres Sexuais , Medula Espinal/fisiologia , Animais , Feminino , Humanos , Masculino , Dor Referida/fisiopatologia , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/fisiopatologia , Estimulação Química
7.
Brain Res ; 1346: 102-11, 2010 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-20595052

RESUMO

Previous studies have shown that the gracile nucleus in postsynaptic dorsal column pathway plays an important role in conveying nociceptive information from pelvic visceral organs. The purpose of this study was to compare effects of a noxious cardiac stimulus on neuronal activity in the cuneate nucleus and upper thoracic spinal cord in rats. Extracellular potentials of single neurons in the cuneate nucleus and upper thoracic (T3) spinal cord were recorded in pentobarbital anesthetized, ventilated and paralyzed male rats. To activate cardiac nociceptors, a silicone tube was placed in the pericardial sac over the left ventricle to administer a solution of bradykinin (10 microg/ml, 0.2 ml, 1 min). The number of cuneate neurons responding to intrapericardial bradykinin (IB, 15.6%, 17/109) was significantly less than for T3 neurons (43.2%, 48/111, P<0.05). IB excited 9/17 (52.9%) cuneate neurons and inhibited eight neurons. In contrast, IB excited a significantly higher percentage of responding spinal neurons than those in cuneate nucleus (43/48, 89.6%, P<0.01). The ratio of short latency/long-lasting responses of cuneate neurons to IB (14/3) were significant higher than responses of spinal neurons (26/22, P<0.05). Spontaneous activity (5.5+/-0.7 imp/s), response amplitudes (6.0+/-0.6 imp/s) and durations (83.4+/-10.8 sec) of cuneate neurons excited by IB were significantly less than for spinal neurons (11.5+/-1.3 imp/s, 20.4+/-2.0 imp/s and 104.9+/-7.0 imp/s, P<0.01, P<0.01, P<0.05), respectively. These results indicate that the cuneate nucleus neurons play a relatively minor role in transmission of cardiac nociceptive information in comparison to upper thoracic spinal neurons.


Assuntos
Coração/fisiologia , Bulbo/fisiologia , Neurônios/fisiologia , Dor/fisiopatologia , Medula Espinal/fisiologia , Animais , Bradicinina/farmacologia , Coração/inervação , Masculino , Isquemia Miocárdica/fisiopatologia , Nociceptores/fisiologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Tratos Espinotalâmicos/citologia , Tratos Espinotalâmicos/fisiologia
8.
Am J Physiol Gastrointest Liver Physiol ; 298(6): G934-42, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20378832

RESUMO

Gastroesophageal reflux (GER) frequently triggers or worsens cardiac pain or symptoms in patients with coronary heart disease. This study aimed to determine whether GER enhances the activity of upper thoracic spinal neurons receiving noxious cardiac input. Gastric fundus and pyloric ligations as well as a longitudinal myelotomy at the gastroesophageal junction induced acute GER in pentobarbital-anesthetized, paralyzed, and ventilated male Sprague-Dawley rats. Manual manipulations of the stomach and lower esophagus were used as surgical controls in another group. At 4-9 h after GER surgery, extracellular potentials of single neurons were recorded from the T3 spinal segment. Intrapericardial bradykinin (IB) (10 microg/ml, 0.2 ml, 1 min) injections were used to activate cardiac nociceptors, and esophageal distensions were used to activate esophageal afferent fibers. Significantly more spinal neurons in the GER group responded to IB compared with the control group (69.1 vs. 38%, P < 0.01). The proportion of IB-responsive neurons in the superficial laminae of GER animals was significantly different from those in deeper layers (1/8 vs. 46/60, P < 0.01); no difference was found in control animals (7/25 vs. 20/46, P > 0.05). Excitatory responses of spinal neurons to IB in the GER group were greater than in the control group [32.4 +/- 3.5 impulses (imp)/s vs. 13.3 +/- 2.3 imp/s, P < 0.01]. Forty-five of 47 (95.7%) neurons responded to cardiac input and ED, which was higher than the control group (61.5%, P < 0.01). These results indicate that acute GER enhanced the excitatory responses of thoracic spinal neurons in deeper laminae of the dorsal horn to noxious cardiac stimulus.


Assuntos
Refluxo Gastroesofágico/patologia , Coração/inervação , Neurônios/fisiologia , Nervos Espinhais/fisiologia , Potenciais de Ação/fisiologia , Vias Aferentes/fisiopatologia , Animais , Esôfago/inervação , Esôfago/patologia , Masculino , Nociceptores , Ratos , Ratos Sprague-Dawley
9.
Brain Res ; 1313: 53-61, 2010 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-19962970

RESUMO

BACKGROUND: It is unclear whether spinal cord stimulation (SCS) at higher frequencies induces further increases in vasodilation and enhances clinical efficacy. OBJECTIVES: This study investigated effects of SCS at both a normal frequency (as used clinically) and two higher frequencies on peripheral vasodilation. METHODS: A unipolar ball electrode was placed on the left dorsal column at the lumbar 2-3 spinal cord segments (L2-L3) in sodium pentobarbital anesthetized, paralyzed, and artificially ventilated rats. Cutaneous blood flow recordings from both ipsilateral (left) and contralateral (right) hind foot pads were measured with laser Doppler flow perfusion monitors. SCS at frequencies of 50, 200, or 500 Hz was applied at 30%, 60%, and 90% of motor threshold (MT) using standard square waves. Resiniferatoxin (RTX: an ultrapotent analog of capsaicin) and a calcitonin gene-related peptide (CGRP) receptor blocker (CGRP(8-37)) was also used to elucidate mechanisms of SCS vasodilation at these higher frequencies. RESULTS: SCS applied with the three frequencies produced similar MT (n=22). SCS at 500 Hz significantly increased cutaneous blood flow and decreased vascular resistance compared to changes induced by frequencies of 50 and 200 Hz (P<0.05, n=8). RTX (2 microg/kg, i.v.) as well as CGRP(8-37) (2.37 mg/kg, i.v.) significantly reduced SCS-induced vasodilation at 500 Hz (P<0.05, n=6) as compared to responses prior to administrations of these drugs. CONCLUSION: SCS at 500 Hz significantly increased SCS-induced vasodilation without influencing MT. Furthermore, effects of SCS at 500 Hz are mediated via activation of TRPV1-containing fibers and a release of CGRP.


Assuntos
Circulação Sanguínea/fisiologia , Pressão Sanguínea/fisiologia , Estimulação Elétrica/métodos , Medula Espinal/fisiologia , Vasodilatação/fisiologia , Animais , Circulação Sanguínea/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/farmacologia , Fármacos Cardiovasculares/farmacologia , Diterpenos/farmacologia , Pé/fisiologia , Membro Posterior/efeitos dos fármacos , Membro Posterior/fisiologia , Vértebras Lombares , Masculino , Fragmentos de Peptídeos/farmacologia , Ratos , Ratos Sprague-Dawley , Fenômenos Fisiológicos da Pele , Medula Espinal/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos
10.
Auton Neurosci ; 145(1-2): 27-34, 2009 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-19027368

RESUMO

The aim of this study was to examine spinal neuronal processing of innocuous and noxious mechanical inputs from the esophagus in diabetic rats. Streptozotocin (50 mg/kg, ip) was used to induce diabetes in 15 male Sprague-Dawley rats, and vehicle (10 mM citrate buffer) was injected into 15 rats as control. Four to eleven weeks after injections, extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated rats. Esophageal distensions (ED, 0.2, 0.4 ml, 20 s) were produced by water inflation of a latex balloon in the thoracic esophagus. Noxious ED (0.4 ml, 20 s) altered activity of 44% (55/126) and 38% (50/132) of spinal neurons in diabetic and control rats, respectively. The short-lasting excitatory responses to ED were encountered more frequently in diabetic rats (27/42 vs 15/41, P<0.05). Spinal neurons with low threshold for excitatory responses to ED were more frequently encountered in diabetic rats (33/42 vs 23/41, P<0.05). However, mean excitatory responses and duration of responses to noxious ED were significantly reduced for high-threshold neurons in diabetic rats (7.4+/-1.1 vs 13.9+/-3.3 imp/s; 19.0+/-2.3 vs 31.2+/-5.5 s; P<0.05). In addition, more large size somatic receptive fields were found for spinal neurons with esophageal input in diabetic rats than in control rats (28/42 vs 19/45, P<0.05). These results suggested that diabetes influenced response characteristics of thoracic spinal neurons receiving mechanical esophageal input, which might indicate an altered spinal visceroceptive processing underlying diabetic esophageal neuropathy.


Assuntos
Diabetes Mellitus Experimental/fisiopatologia , Esôfago/fisiopatologia , Neurônios/fisiologia , Nervos Espinhais/fisiologia , Tórax/inervação , Animais , Diabetes Mellitus Experimental/complicações , Dilatação Patológica/complicações , Dilatação Patológica/fisiopatologia , Esôfago/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Tórax/fisiologia
11.
Brain Res ; 1207: 73-83, 2008 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-18374907

RESUMO

BACKGROUND AND AIMS: SCS is used to improve peripheral circulation in selected patients with ischemia of the extremities. However the mechanisms are not fully understood. The present study investigated whether blockade of ERK and AKT activation modulated SCS-induced vasodilation. METHODS: A unipolar ball electrode was placed on the left dorsal column at the lumbar 2-3 spinal segments in rats. Cutaneous blood flows from left and right hind foot pads were recorded with laser Doppler flow perfusion monitors. SCS was applied through a ball electrode at 60% or 90% of MT. U0126, an inhibitor of ERK kinase, or LY294002, an inhibitor of PI3K upstream of AKT, was applied to the lumbar 3-5 spinal segments (n=7, each group). RESULTS: U0126 (100 nM, 5 microM and 250 microM) significantly attenuated SCS-induced vasodilation at 60% (100 nM: P<0.05; 5 microM and 250 microM: P<0.01, respectively) and 90% of MT (100 nM and 5 microM: P<0.05; 250 microM: P<0.01, respectively). LY294002 at 100 microM also attenuated SCS-induced vasodilation at 60% and 90% of MT (P<0.05). CONCLUSIONS: These data suggest that ERK and AKT pathways are involved in SCS-induced vasodilation.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia , Medula Espinal/fisiologia , Vasodilatação/fisiologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Pressão Sanguínea/efeitos da radiação , Butadienos/farmacologia , Cromonas/farmacologia , Relação Dose-Resposta a Droga , Estimulação Elétrica/métodos , Inibidores Enzimáticos/farmacologia , Fluxometria por Laser-Doppler/métodos , Masculino , Morfolinas/farmacologia , Nitrilas/farmacologia , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Fluxo Sanguíneo Regional/efeitos da radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Medula Espinal/efeitos dos fármacos , Medula Espinal/efeitos da radiação , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Resistência Vascular/efeitos da radiação , Vasodilatação/efeitos dos fármacos , Vasodilatação/efeitos da radiação
12.
Am J Physiol Gastrointest Liver Physiol ; 294(3): G708-16, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18187515

RESUMO

Esophageal hypersensitivity is one of the most common causes of noncardiac chest pain in patients. In this study, we investigated whether exposure of the esophagus to acid and other chemical irritants affected activity of thoracic spinal neurons responding to esophageal distension (ED) in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital sodium-anesthetized, -paralyzed, and -ventilated male rats. ED (0.2 or 0.4 ml, 20 s) was produced by water inflation of a latex balloon placed orally into the middle thoracic region of the esophagus. The chemicals were administered via a tube that was passed through the stomach and placed in the thoracic esophagus. To irritate the esophagus, 0.2 ml of HCl (0.01 N), bradykinin (10 microg/ml), or capsaicin (10 microg/ml) were injected for 1-2 min. Only neurons excited by ED were included in this study. Results showed that intraesophageal instillation of HCl, bradykinin, and capsaicin increased activity in 3/20 (15%), 7/25 (28%), and 9/20 (45%) neurons but enhanced excitatory responses to ED in 9/17 (53%), 8/15 (53%), and 7/11 (64%) of the remaining spinal neurons, respectively. Furthermore, intraesophageal chemicals were more likely to enhance the responsiveness of low-threshold neurons than high-threshold neurons to the esophageal mechanical stimulus. Normal saline (pH 7.4, 0.2 ml) or vehicle instilled in the esophagus did not significantly affect activity or ED responses of neurons. We conclude that enhanced responses of thoracic spinal neurons to ED by the chemically challenged esophagus may provide a possible pathophysiological basis for visceral hypersensitivity in patients with gastroesophageal reflux and/or esophagitis.


Assuntos
Esôfago/efeitos dos fármacos , Neurônios/fisiologia , Medula Espinal/fisiologia , Animais , Bradicinina/administração & dosagem , Bradicinina/farmacologia , Capsaicina/farmacologia , Cateterismo , Esôfago/inervação , Esôfago/fisiologia , Espaço Extracelular/fisiologia , Ácido Clorídrico/farmacologia , Injeções , Masculino , Estimulação Física , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia
13.
J Pain ; 9(1): 71-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17974489

RESUMO

UNLABELLED: Clinical studies have shown that neuromodulation therapies, such as spinal cord stimulation (SCS) and transcutaneous electrical nerve stimulation (TENS), reduce symptoms of chronic neuropathic and visceral pain. The neural mechanisms underlying SCS and TENS therapy are poorly understood. The present study was designed to compare the effects of SCS and TENS on spinal neuronal responses to noxious stimuli applied to the heart and esophagus. Direct stimulation of an intercostal nerve (ICNS) was used to simulate the effects of TENS. Extracellular potentials of left thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. SCS (50 Hz, 0.2 ms, 3-5 minutes) at a clinical relevant intensity (90% of motor threshold) was applied on the C1-C2 or C8-T1 ipsilateral spinal segments. Intercostal nerve stimulation (ICNS) at T3 spinal level was performed using the same parameters as SCS. Intrapericardial injection of bradykinin (IB, 10 microg/mL, 0.2 mL, 1 minute) was used as the noxious cardiac stimulus. Noxious thoracic esophageal distension (ED, 0.4 mL, 20 seconds) was produced by water inflation of a latex balloon. C1-C2 SCS suppressed excitatory responses of 16/22 T3 spinal neurons to IB and 25/30 neurons to ED. C8-T1 SCS suppressed excitatory responses of 10/15 spinal neurons to IB and 17/23 neurons to ED. ICNS suppressed excitatory responses of 9/12 spinal neurons to IB and 17/22 neurons to ED. These data showed that SCS and ICNS modulated excitatory responses of T3 spinal neurons to noxious stimulation of the heart and esophagus. PERSPECTIVE: Neuromodulation of noxious cardiac and esophageal inputs onto thoracic spinal neurons by spinal cord and intercostal nerves stimulation observed in the present study may help account for therapeutic effects on thoracic visceral pain by activating the spinal dorsal column or somatic afferents.


Assuntos
Terapia por Estimulação Elétrica/métodos , Nociceptores/fisiologia , Manejo da Dor , Dor/fisiopatologia , Medula Espinal/fisiologia , Fibras Aferentes Viscerais/fisiologia , Potenciais de Ação/fisiologia , Vias Aferentes/fisiologia , Angina Pectoris/fisiopatologia , Angina Pectoris/terapia , Animais , Esôfago/inervação , Esôfago/fisiopatologia , Coração/inervação , Coração/fisiopatologia , Masculino , Inibição Neural/fisiologia , Neurônios Aferentes/fisiologia , Células do Corno Posterior/fisiologia , Ratos , Ratos Sprague-Dawley , Nervos Espinhais/fisiologia
14.
Neurosci Lett ; 428(1): 38-42, 2007 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-17942225

RESUMO

The aim of this study was to determine whether spinal cord stimulation (SCS) modulates activity of lumbosacral spinal neurons receiving input from the urinary bladder. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms, 3-5 min, 90% motor threshold) was applied on the dorsal column of L2-L3 and C1-C2 segments and significantly reduced excitatory responses of 18/25 (72%) and 13/19 (68%) lumbosacral neurons to noxious urinary bladder distension (UBD, > or =1.0 ml, 20 s), respectively. SCS affected spinal neurons with either high- or low-threshold responses to UBD. These results suggested that SCS might have a potential therapeutic effect for patients with hypersensitivity and/or pain of cystitis and other urinary bladder disorders.


Assuntos
Estimulação Elétrica/métodos , Neurônios/fisiologia , Medula Espinal/citologia , Medula Espinal/fisiologia , Bexiga Urinária/inervação , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Vias Aferentes/fisiologia , Animais , Laminectomia/métodos , Região Lombossacral , Masculino , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/fisiologia
15.
Am J Physiol Regul Integr Comp Physiol ; 293(5): R2052-8, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17761515

RESUMO

The purpose of the present study was to determine whether an intraspinal nociceptive pathway from the lungs modulated activity of spinal neurons that also received afferent input from the colon. Extracellular potentials of single lumbosacral (L6-S2) spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. The lower airways and lungs were irritated by injecting ammonia vapor over a 30% NH(4)OH solution into the inspiratory line of the ventilator (0.5 ml, 20 s). Graded colorectal distension (CRD; 20-60 mmHg, 20 s) was produced by air inflation of a balloon. Inhaled ammonia (IA) altered activity of 31/51 (61%) lumbosacral spinal neurons responding to noxious CRD (60 mmHg, 20 s). In contrast, IA changed activity of 3/30 (10%) spinal neurons with somatic fields that did not respond to colorectal inputs. IA decreased activity of 16/31 (52%) spinal neurons and increased activity of the other 15 neurons with colorectal input. Multiple patterns of viscerovisceral convergent spinal neurons with excitatory and inhibitory responses to CRD and IA were observed; 87% (27/31) of the viscerovisceral convergent neurons also responded to innocuous and/or noxious stimuli of somatic fields. Bilateral cervical vagotomy abolished responses to IA in 2/8 tested neurons, indicating that the remaining 6 neurons had input originating from sympathetic afferent fibers. Rostral C1 spinal transection did not abolish inhibitory responses to IA in 4/4 neurons, but L2 transection eliminated inhibitory responses to IA in 3/3 neurons. These results indicated that irritation of the lower airways modulated activity of lumbosacral spinal neurons with colorectal input. It might contribute to intraspinal cross talk between the colon and lungs.


Assuntos
Colo/inervação , Colo/fisiologia , Irritantes/toxicidade , Pulmão/fisiologia , Neurônios/efeitos dos fármacos , Medula Espinal/efeitos dos fármacos , Administração por Inalação , Vias Aferentes/efeitos dos fármacos , Amônia/toxicidade , Animais , Eletrofisiologia , Irritantes/administração & dosagem , Região Lombossacral , Pulmão/efeitos dos fármacos , Masculino , Vias Neurais/efeitos dos fármacos , Nociceptores/efeitos dos fármacos , Estimulação Física , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Vagotomia , Nervo Vago/fisiologia
16.
Brain Res ; 1156: 80-92, 2007 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-17540346

RESUMO

BACKGROUND: Spinal cord stimulation (SCS) is used to relieve ischemic pain and improve peripheral blood flow in selected patients with peripheral arterial diseases. Our previous studies show that antidromic activation of transient receptor potential vanilloid-1 (TRPV1) containing sensory fibers importantly contributes to SCS-induced vasodilation. OBJECTIVES: To determine whether peripheral terminals of TRPV1 containing sensory fibers produces vasodilation that depends upon the release of calcitonin gene-related peptide (CGRP) and nitric oxide (NO) during SCS. METHODS: A unipolar ball electrode was placed on the left dorsal column at lumbar spinal cord segments 2-3 in sodium pentobarbital anesthetized, paralyzed and ventilated rats. Cutaneous blood flow from left and right hindpaws was recorded with laser Doppler flow perfusion monitors. SCS was applied through a ball electrode at 30%, 60%, 90% and 300% of motor threshold. Resiniferatoxin (RTX; 2 microg/ml, 100 microl), an ultra potent analog of capsaicin, was injected locally into the left hindpaw to functionally inactivate TRPV-1 containing sensory terminals. In another set of experiments, CGRP(8-37), an antagonist of the CGRP-1 receptor, was injected at 0.06, 0.12 or 0.6 mg/100 microl into the left hindpaw to block CGRP responses; N-omega-nitro-l-arginine methyl ester (L-NAME), a nonselective nitric-oxide synthase (NOS) inhibitor, was injected at 0.02 or 0.2 mg/100 microl into the left hindpaw to block nitric oxide synthesis; (4S)-N-(4-Amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine, TFA, a neuronal NOS inhibitor, was injected at 0.02 or 0.1 mg/100 microl into the left hindpaw to block neuronal nitric oxide synthesis. RESULTS: SCS at all intensities produced vasodilation in the left hindpaw, but not in the right. RTX administration attenuated SCS-induced vasodilation at all intensities in the left hindpaw (P<0.05, n=7) compared with responses before RTX. CGRP(8-37) administration attenuated SCS-induced vasodilation in the left hindpaw in a dose dependent manner (linear regression, P<0.05) compared with responses before CGRP(8-37). In addition, L-NAME at a high dose, but not (4S)-N-(4-Amino-5[aminoethyl]aminopentyl)-N'-nitroguanidine, TFA, decreased SCS-induced vasodilation (P<0.05, n=5). CONCLUSION: While TRPV1, CGRP and NO are known to be localized in the same nerve terminals, our data indicate that SCS-induced vasodilation depends on CGRP release, but not NO release. NO, released from endothelial cells, may be associated with vascular smooth muscle relaxation and peripheral blood flow increase in response to SCS.


Assuntos
Vias Neurais/fisiologia , Medula Espinal/fisiologia , Canais de Cátion TRPV/fisiologia , Vasodilatação/fisiologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Estimulação Elétrica , Potenciais Evocados/fisiologia , Membro Posterior/lesões , Vértebras Lombares , NG-Nitroarginina Metil Éster/farmacologia , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/fisiologia , Neurônios Aferentes/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Ratos , Pele/irrigação sanguínea , Medula Espinal/irrigação sanguínea , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasodilatação/efeitos dos fármacos
17.
J Pain ; 8(6): 522-9, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17434802

RESUMO

UNLABELLED: The aim of this study was to examine whether gastric afferent information converged onto upper thoracic spinal neurons that received noxious cardiac input. Extracellular potentials of single upper thoracic (T3) spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, ventilated male rats. Gastric distension (GD) (20, 40, 60 mm Hg, 20 seconds) was produced by air inflation of a latex balloon surgically placed in the stomach. A catheter was placed in the pericardial sac to administer bradykinin solution (10 microg/mL, 0.2 mL, 1 minute) as a noxious cardiac stimulus. Noxious GD (> or =40 mm Hg) altered activity of 26 of 31 (84%) spinal neurons receiving cardiac input. Twenty-two (85%) gastrocardiac convergent neurons were excited, and 1 neuron was inhibited by both intrapericardial bradykinin and GD; the remainder exhibited biphasic response patterns. Twenty-three of 26 (88%) gastrocardiac neurons also received convergent somatic input from the chest, triceps, and upper back areas. Bilateral cervical vagotomy did not significantly affect excitatory responses to GD in 5 of 5 neurons tested. Spinal transection at the C1 segment after vagotomy did not affect excitatory responses to GD in 3 of 4 neurons but abolished the GD response in 1 neuron. These data showed that a gastric stimulus excited T3 spinal neurons with noxious cardiac input primarily by way of intraspinal ascending pathways. PERSPECTIVE: Convergence of gastric afferent input onto upper thoracic spinal neurons receiving noxious cardiac input that was observed in the present study may provide a spinal mechanism that explains stomach-heart cross-organ communication, such as postprandial triggering and worsening of angina pectoris in patients with coronary artery disease.


Assuntos
Angina Pectoris/fisiopatologia , Coração/inervação , Células do Corno Posterior/fisiopatologia , Estômago/inervação , Fibras Aferentes Viscerais/fisiopatologia , Potenciais de Ação/fisiologia , Vias Aferentes/fisiopatologia , Animais , Bradicinina/efeitos adversos , Digestão/fisiologia , Mediadores da Inflamação/efeitos adversos , Masculino , Nociceptores/fisiopatologia , Estimulação Física , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/fisiopatologia , Pele/inervação , Estômago/fisiopatologia , Vértebras Torácicas , Nervo Vago/fisiopatologia , Nervo Vago/cirurgia
18.
Brain Res ; 1141: 84-91, 2007 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-17280649

RESUMO

Respiratory symptoms experienced in some patients with cardiac diseases may be due to convergence of noxious cardiac and pulmonary inputs onto neurons of the central nervous system. For example, convergence of cardiac and respiratory inputs onto single solitary tract neurons may be in part responsible for integration of regulatory and defensive reflex control. However, it is unknown whether inputs from the lungs and heart converge onto single neurons of the spinal cord. The present aim was to characterize upper thoracic spinal neurons responding to both noxious stimuli of the heart and lungs in rats. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. A catheter was placed in the pericardial sac to administer bradykinin (BK, 10 microg/ml, 0.2 ml, 1 min) as a noxious cardiac stimulus. The lung irritant, ammonia, obtained as vapor over a 30% solution of NH(4)OH was injected into the inspiratory line of the ventilator (0.5-1.0 ml over 20 s). Intrapericardial bradykinin (IB) altered activity of 58/65 (89%) spinal neurons that responded to inhaled ammonia (IA). Among those cardiopulmonary convergent neurons, 81% (47/58) were excited by both IA and IB, and the remainder had complex response patterns. Bilateral cervical vagotomy revealed that vagal afferents modulated but did not eliminate responses of individual spinal neurons to IB and IA. The convergence of pulmonary and cardiac nociceptive signaling in the spinal cord may be relevant to situations where a disease process in one organ influences the behavior of the other.


Assuntos
Vias Aferentes/fisiologia , Coração/inervação , Neurônios/fisiologia , Medula Espinal/citologia , Tórax/inervação , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Amônia/farmacologia , Animais , Bradicinina/farmacologia , Masculino , Estimulação Física/métodos , Ratos , Ratos Sprague-Dawley , Estimulação Química , Fatores de Tempo , Vagotomia/métodos
19.
Auton Neurosci ; 131(1-2): 77-86, 2007 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-16935568

RESUMO

The occurrence of vagally mediated afferent signaling by lung irritants is well known. However, spinal visceral afferent pathways also might be relevant to pulmonary irritation. In the present study, responses and modulation of superficial and deep T3 spinal neurons were examined using inhaled ammonia, and the peripheral afferent fibers were also characterized in part. Extracellular potentials of single thoracic (T3) spinal neurons were recorded in pentobarbital anesthetized, paralyzed, and ventilated male rats. Ammonia vapor (0.5, 1.0, 2.0 ml) was injected into the inspiratory line of the ventilator for 20 s. Inhaled ammonia (IA, 1.0 ml) excited 5/6 neurons and inhibited one spinal neuron recorded in superficial laminae, whereas deeper neurons responded with excitatory (E, n = 20), inhibitory (I, n = 4) or biphasic patterns (6 E-I, 3 I-E). Electrical and chemical stimulation of C1-C2 spinal neurons primarily suppressed T3 neuronal responses to IA. Resiniferatoxin (2 microg/kg, i.v.), which desensitizes afferent fibers containing transient receptor potential vanilloid receptor-1 (TRPV-1), abolished excitatory responses of 8/8 neurons to IA. Bilateral cervical vagotomy did not affect IA responses in 5 superficial neurons while 7 deeper neurons showed variable responses. 82% (32/39) of the spinal neurons responding to IA also received convergent noxious inputs from somatic fields in the chest and back areas. These results suggested that superficial and deeper spinal neuronal activation by inhaled ammonia mainly depended upon pulmonary sympathetic afferent fibers expressing TRPV-1. Additionally, C1-C2 spinal neurons, supraspinal sites and vagal afferents modulated the thoracic spinal neuronal responses to lower airway irritation.


Assuntos
Vias Aferentes/fisiologia , Pulmão/inervação , Neurônios Aferentes/fisiologia , Medula Espinal/citologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Amônia/efeitos adversos , Animais , Laminectomia/métodos , Pulmão/efeitos dos fármacos , Masculino , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Ratos , Ratos Sprague-Dawley , Região Sacrococcígea , Estimulação Química , Fatores de Tempo , Vagotomia/métodos
20.
Auton Neurosci ; 133(2): 121-7, 2007 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-17169618

RESUMO

Inhalation of ammonia influences the activity of slowly adapting airway receptors (SARs), but the mechanism(s) is uncertain. Release of inflammatory mediators by transient receptor potential vanilloid receptor-1 (TRPV1) containing nerve endings could affect SAR response to ammonia. We examined how sensitization and subsequent desensitization of the TRPV1 by resiniferatoxin (RTX), affected the responses of SARs to inhaled ammonia. In pentobarbital-anesthetized, paralyzed and artificially ventilated rats, the left cervical vagus nerve was exposed, sectioned rostrally, and desheathed. Single fibers of SARs were identified and recorded. Two milliliters of ammonia vapor (from a 30% NH(4)OH solution) was inhaled over 20 s and responses to ammonia were measured. RTX was injected intravenously at 2 microg/Kg. Twenty minutes later, ammonia inhalation was repeated. Isoproterenol (ISO, 100 microg/kg, i.v.) was used in another set of experiments to block possible ammonia-induced bronchoconstriction. Ammonia increased tonic activity of SARs (n=10, P<0.0001), with complex changes in ventilator-related activity. SAR firing rate began to increase 2.3+/-0.2 min after RTX and returned to control levels at 13.6+/-1.4 min (n=10). By 20 min after RTX cardiovascular responses to ammonia were abolished, but effects on SAR activity were essentially unchanged. ISO did not modify the response of SARs to ammonia (n=8). These data suggest that responses of SARs to ammonia in rats do not depend on release of mediators by nerve endings containing TRPV1 and are not secondary to bronchoconstriction. However, when TRPV1 containing nerve endings were initially activated by RTX, the release of mediators may have affected SAR discharges.


Assuntos
Amônia/efeitos adversos , Brônquios/efeitos dos fármacos , Células Quimiorreceptoras/efeitos dos fármacos , Fenômenos Fisiológicos Respiratórios/efeitos dos fármacos , Células Receptoras Sensoriais/efeitos dos fármacos , Canais de Cátion TRPV/efeitos dos fármacos , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/fisiologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Brônquios/inervação , Brônquios/fisiologia , Broncoconstrição/efeitos dos fármacos , Broncoconstrição/fisiologia , Células Quimiorreceptoras/fisiologia , Diterpenos/farmacologia , Masculino , Nociceptores/efeitos dos fármacos , Nociceptores/fisiologia , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/fisiologia , Canais de Cátion TRPV/metabolismo , Nervo Vago/efeitos dos fármacos , Nervo Vago/fisiologia , Fibras Aferentes Viscerais/efeitos dos fármacos , Fibras Aferentes Viscerais/fisiologia
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