Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 6 de 6
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Neurotrauma ; 40(23-24): 2552-2565, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36785968

RESUMO

Research has shown that engaging pain (nociceptive) pathways after spinal cord injury (SCI) aggravates secondary injury and undermines locomotor recovery. This is significant because SCI is commonly accompanied by additional tissue damage (polytrauma) that drives nociceptive activity. Cutting communication with the brain by means of a surgical transection, or pharmacologically transecting the cord by slowly infusing a sodium channel blocker (lidocaine) rostral to a thoracic contusion, blocks pain-induced hemorrhage. These observations suggest that the adverse effect of pain after SCI depends on supraspinal (brain) systems. We hypothesize that inhibiting brain activity using a general anesthetic (e.g., pentobarbital, isoflurane) should have a protective effect. The present study shows that placing rats in an anesthetic state with pentobarbital or isoflurane 24 h after a lower thoracic contusion injury blocks pain-induced intraspinal inflammation and hemorrhage when administered before pain. Pentobarbital also extends protective effects against locomotor deficits produced by noxious stimulation. Inducing anesthesia after noxious stimulation, however, has no effect. Similarly, subanesthetic dosages of pentobarbital were also ineffective at blocking pain-induced hemorrhage. Also examined were the hemodynamic impacts of both pain and anesthetic delivery after SCI. Peripheral pain-input induced an acute increase in systolic blood pressure; isoflurane and pentobarbital prevent this increase, which may contribute to the protective effect of anesthesia. The results suggest that placing patients with SCI in a state akin to a medically induced coma can have a protective effect that blocks the adverse effects of pain.


Assuntos
Anestésicos , Contusões , Isoflurano , Traumatismos da Medula Espinal , Humanos , Ratos , Animais , Pentobarbital , Isoflurano/farmacologia , Dor/tratamento farmacológico , Dor/etiologia , Traumatismos da Medula Espinal/complicações , Anestesia Geral/efeitos adversos , Hemorragia , Contusões/complicações
2.
J Neurotrauma ; 37(15): 1729-1739, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32368946

RESUMO

Spinal cord injury (SCI) is often accompanied by additional tissue damage (polytrauma), which engages pain (nociceptive) fibers. Prior research has shown that nociceptive input can increase cell death, expand the area of hemorrhage, and impair long-term recovery. The current study shows that these adverse effects can be blocked by the sodium channel blocker lidocaine applied rostral to a contusion injury. Rats received a lower thoracic (T12) contusion injury, and noxious electrical stimulation (shock) was applied to the tail 24 h later. Immediately before shock treatment, a pharmacological transection was performed by slowly infusing lidocaine at T2. Long-term locomotor recovery was assessed over the next 21 days. Noxious electrical stimulation impaired locomotor recovery, and this effect was blocked by rostral lidocaine. Next, the acute effect of lidocaine was assessed. Tissue was collected 3 h after noxious stimulation, and the extent of hemorrhage was evaluated by assessing hemoglobin content using Western blotting. Nociceptive stimulation increased the extent of hemorrhage. Lidocaine applied at T2 before, but not immediately after, stimulation blocked this effect. A similar pattern of results was observed when lidocaine was applied at the site of injury by means of a lumbar puncture. The results show that a pharmacological transection blocks nociception-induced hemorrhage and exacerbation of locomotor deficits.


Assuntos
Encéfalo/efeitos dos fármacos , Hemorragia/tratamento farmacológico , Lidocaína/administração & dosagem , Locomoção/efeitos dos fármacos , Dor/prevenção & controle , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Anestésicos Locais/administração & dosagem , Animais , Encéfalo/fisiologia , Hemorragia/etiologia , Hemorragia/fisiopatologia , Locomoção/fisiologia , Dor/etiologia , Dor/fisiopatologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley , Medula Espinal/fisiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/fisiopatologia , Vértebras Torácicas/lesões , Bloqueadores do Canal de Sódio Disparado por Voltagem/administração & dosagem
3.
Pain ; 147(1-3): 265-76, 2009 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19853381

RESUMO

Central neuropathic pain (CNP) developing after spinal cord injury (SCI) is described by the region affected: above-level, at-level and below-level pain occurs in dermatomes rostral, at/near, or below the SCI level, respectively. People with SCI and rodent models of SCI develop above-level pain characterized by mechanical allodynia and thermal hyperalgesia. Mechanisms underlying this pain are unknown and the goals of this study were to elucidate components contributing to the generation of above-level CNP. Following a thoracic (T10) contusion, forelimb nociceptors had enhanced spontaneous activity and were sensitized to mechanical and thermal stimulation of the forepaws 35 days post-injury. Cervical dorsal horn neurons showed enhanced responses to non-noxious and noxious mechanical stimulation as well as thermal stimulation of receptive fields. Immunostaining dorsal root ganglion (DRG) cells and cord segments with activating transcription factor 3 (ATF3, a marker for neuronal injury) ruled out neuronal damage as a cause for above-level sensitization since few C8 DRG cells expressed AFT3 and cervical cord segments had few to no ATF3-labeled cells. Finally, activated microglia and astrocytes were present in thoracic and cervical cord at 35 days post-SCI, indicating a rostral spread of glial activation from the injury site. Based on these data, we conclude that peripheral and central sensitization as well as reactive glia in the uninjured cervical cord contribute to CNP. We hypothesize that reactive glia in the cervical cord release pro-inflammatory substances which drive chronic CNP. Thus a complex cascade of events spanning many cord segments underlies above-level CNP.


Assuntos
Neuralgia/etiologia , Limiar da Dor/fisiologia , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Medula Espinal/fisiopatologia , Potenciais de Ação/fisiologia , Fator 3 Ativador da Transcrição/metabolismo , Animais , Comportamento Animal , Contagem de Células/métodos , Modelos Animais de Doenças , Membro Anterior/fisiopatologia , Gânglios Espinais/metabolismo , Gânglios Espinais/fisiologia , Hiperalgesia/fisiopatologia , Técnicas In Vitro , Masculino , Nociceptores/patologia , Nociceptores/fisiologia , Estimulação Física/métodos , Ratos , Ratos Sprague-Dawley , Células Receptoras Sensoriais/fisiologia , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Estatísticas não Paramétricas
4.
Behav Brain Res ; 179(2): 281-93, 2007 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-17383022

RESUMO

Nociceptive stimulation, at an intensity that elicits pain-related behavior, attenuates recovery of locomotor and bladder functions, and increases tissue loss after a contusion injury. These data imply that nociceptive input (e.g., from tissue damage) can enhance the loss of function after injury, and that potential clinical treatments, such as pretreatment with an analgesic, may protect the damaged system from further secondary injury. The current study examined this hypothesis and showed that a potential treatment (morphine) did not have a protective effect. In fact, morphine appeared to exacerbate the effects of nociceptive stimulation. Experiment 1 showed that after spinal cord injury 20mg/kg of systemic morphine was necessary to induce strong antinociception and block behavioral reactivity to shock treatment, a dose that was much higher than that needed for sham controls. In Experiment 2, contused rats were given one of three doses of morphine (Vehicle, 10, 20mg/kg) prior to exposure to uncontrollable electrical stimulation or restraint alone. Despite decreasing nociceptive reactivity, morphine did not attenuate the long-term consequences of shock. Rats treated with morphine and shock had higher mortality rates, and displayed allodynic responses to innocuous sensory stimuli three weeks later. Independent of shock, morphine per se undermined recovery of sensory function. Rats treated with morphine alone also had significantly larger lesions than those treated with saline. These results suggest that nociceptive stimulation affects recovery despite a blockade of pain-elicited behavior. The results are clinically important because they suggest that opiate treatment may adversely affect the recovery of function after injury.


Assuntos
Analgésicos Opioides/farmacologia , Morfina/farmacologia , Dor/tratamento farmacológico , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Análise de Variância , Animais , Distribuição de Qui-Quadrado , Humanos , Masculino , Dor/complicações , Limiar da Dor/efeitos dos fármacos , Limiar da Dor/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/complicações
5.
Behav Neurosci ; 119(2): 538-47, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15839800

RESUMO

Following spinal transection of the upper thoracic spinal cord, male Sprague-Dawley rats given legshock whenever a hindlimb is extended learn to maintain the leg in a flexed position. The region of the cord that mediates this instrumental learning was isolated using neuroanatomical tracing, localized infusion of lidocaine, and surgical transections. DiI and Fluoro-Gold microinjection at the site of shock application labeled motor neuron bodies of lamina IX in the lower lumbar region. Local application of the Na-super++ channel blocker lidocaine disrupted learning when it was applied over a region extending from the lower lumbar (L3) to upper sacral (S2) cord. The drug had no effect rostral or caudal to this region. Surgical transections as low as L4 had no effect on learning. Learning also survived a dual transection at L4 and S3, but not L4 and S2. The results suggest that the essential neural circuit lies between L4 and S3.


Assuntos
Condicionamento Operante , Medula Espinal/fisiologia , Animais , Membro Posterior , Região Lombossacral , Masculino , Plasticidade Neuronal , Ratos , Ratos Sprague-Dawley , Reforço Psicológico , Região Sacrococcígea , Medula Espinal/cirurgia , Nervos Espinhais/fisiologia
6.
Psychopharmacology (Berl) ; 175(1): 47-52, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15060758

RESUMO

RATIONALE: Exposure to moderate tail shock [3, 0.75 s, 1 mA, 20 s interstimulus interval (ISI)] can enhance pain reactivity (hyperalgesia) in rats. This hyperalgesia reflects an unconditioned response that transfers across contexts and is associated with enhanced Pavlovian fear conditioning to aversive unconditioned stimuli (US). It is possible that moderate shock also enhances learning about appetitive stimuli such as a reinforcing drug. OBJECTIVES: The present study examined the effect of moderate shock exposure on unconditioned psychomotor activation and appetitive conditioning using a morphine place-preference task. METHODS: During training, rats were given moderate shock or restraint and then received subcutaneous morphine at one of four doses (0.0, 0.2, 1.0, or 5.0 mg/kg) and were transferred to a conditioning apparatus. Five hours later, animals were given discrimination training in a different context. Animals received 2 days of training, each separated by a day of testing for preference. To test the impact of shock on psychomotor activation, subjects were given shock or restraint and one of two doses of morphine (0.0 mg/kg or 5.0 mg/kg) and placed in a box to monitor activity. RESULTS: Vehicle-treated shocked rats showed a conditioned place aversion. Subjects that received morphine showed a dose-dependent place preference that was facilitated by moderate shock exposure. Shock also enhanced the motor activation produced by morphine. CONCLUSIONS: These results indicate that the affective state produced by moderate shock has a negative valence that is sufficient to support a conditioned place aversion. This state is associated with a general sensitization that enhances processing of appetitive US.


Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Morfina/farmacologia , Atividade Motora/efeitos dos fármacos , Entorpecentes/farmacologia , Choque/psicologia , Animais , Condicionamento Psicológico/fisiologia , Relação Dose-Resposta a Droga , Masculino , Morfina/administração & dosagem , Atividade Motora/fisiologia , Entorpecentes/administração & dosagem , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Reforço Psicológico , Cauda
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...