The Role of Protease Activated Receptors and Proteases in Subtly Inflamed Diarrhea-Predominant Irritable Bowel Syndrome / 대한소화기학회지

No abstract available.

Actividad espontánea de nociceptores cutáneos en pacientes con neuropatía de fibras delgadas / Spontaneous activity of cutaneous nociceptors in patients with painful polyneuropathy. Report of three patients

Background: Painful polyneuropathy may result from selective impairment of small diameter nerve fibers, while tactile and motor functions are preserved. In these patients clinical and electrophysiological assessment is usually unrevealing. We report three patients with a pure painful polyneuropathy. One of them had neurogenic pruritus additionally. Quantitative sensory analysis disclosed a slight warm hypoesthesia (3/3) and paradoxical hot sensation (2/3) in the feet. Intraneural recordings from the peroneal nerve demonstrated abnormal spontaneous activity in 8 of 17 nociceptive afferents. One of them displayed double firing reflecting impulse multiplication. These results support the notion that patients with pain or pruritus with a distal distribution similar to a polyneuropathy, could have small diameter afferent fiber damage, despite normal function of large diameter fibers.

Treinamento com natação sobre a avaliação funcional da nocicepção ciática em ratos / Swimming training and functional assessment of sciatic nociception in rats

INTRODUÇÃO: Existe certa controvérsia com relação ao efeito protetor do exercício em indivíduos com neuropatia periférica. OBJETIVO: Avaliar o treinamento físico, moderado e com intensidade progressiva, como fator infl uenciador da nocicepção em ratos submetidos a um modelo de ciatalgia. MATERIAIS E MÉTODOS: Foram utilizados 18 ratos, divididos em três grupos: Grupo-Controle (PL); Grupo Natação Baixa Intensidade (GNBI); Grupo Natação Tempo Progressivo (GNTP). Para a realização dos protocolos de treinamento, os animais foram colocados em tanque de água, durante 6 semanas, 3 dias da semana, sendo que para GNBI os animais realizavam 10 minutos de natação por dia, para GNTP os animais iniciaram com 10 minutos e tendo progressão de 10 minutos por semana. PL realizava menos de 1 minuto de natação, apenas para ambientalização. Após o treinamento foi realizado o modelo experimental de ciatalgia, com amarria por fio Catgut cromado. Para avaliação da nocicepção foi utilizado o Teste de Incapacidade Funcional, que mostra os valores de tempo de elevação da pata (TEP) em um minuto. As avaliações ocorreram antes da cirurgia, no 3º, 6º e 10º dias de pós-operatório (PO). RESULTADOS: Para todos os grupos, foi possível observar que houve aumento significativo dos valores no 3º, 6º e 10º dias de PO ao comparar com os valores do momento pré-cirurgia, mas, para o controle, não houve alteração significativa entre os momentos seguintes, fato que ocorreu para os grupos de natação. CONCLUSÃO: O exercício produziu maior hiperalgesia do que nos animais controle.

INTRODUCTION: The protective effect of exercise on individuals with peripheral neuropathy is controversial. OBJECTIVE: To assess the influence of physical training of moderate and progressive intensity on nociception of rats in an experimental sciatica model. MATERIALS AND METHODS: The study assessed 18 rats divided into the following three groups: control group (CG); low-intensity swimming group (LISG); progressive-time swimming group (PTSG). To meet the physical training protocol, the animals were placed in a water tank for six weeks, three alternate days per week. In LISG group, the animals swam ten minutes per session, and, in PTSG group, the animals began swimming for ten minutes, and had a ten-minute increase per week. In CG group, the animals swam less than one minute per day, only to get used to the water environment. After finishing the swimming training, the experimental sciatica model protocol was started with constrictive ligature of the sciatic nerve with chromic catgut. Nociception was assessed using the functional disability test, which measures, in a one-minute interval, the time during which the animal holds its hind paw (THHP) in a guarded position. Assessments were performed preoperatively, and on the third, sixth, and tenth post-operative (PO) days. RESULTS: All groups showed a significant increase in THHP on third, sixth, and tenth PO days, as compared to preoperative values. In CG, no significant change was observed in PO assessments, unlike what happened in LISG and PTSG groups. CONCLUSION: Exercise produced greater hyperalgesia.

Antagonistas serotoninérgico e noradrenérgico por via subaracnoidea aumentam a resposta álgica em ratos / Subarachnoid serotonergic and noradrenergic antagonists increase the pain response in rats

JUSTIFICATIVA E OBJETIVOS: Há evidências de que a passagem de informações nociceptivas pelo corno posterior da medula espinhal (CPME) seguindo para níveis rostrais do sistema nervoso central sofre profundas influências excitatórias e inibitórias. A presente pesquisa teve como objetivo comparar os efeitos da metissergida, da fentolamina e da fentolamina associada à metissergida, administrados por via subaracnoidea, sobre as fases I, intermediária e II do teste da formalina modificado em ratos. MÉTODO: Foram utilizados 28 ratos Wistar machos, distribuídos aleatoriamente em quatro grupos (n = 7) para receber solução salina (GC), fentolamina (GF), metissergida (GM) ou fentolamina associada à metissergida (GFM) por via subaracnoidea. A dor foi induzida pela administração de formalina na região dorsal da pata posterior direita. O teste foi dividido em três fases; fase I, intermediária e fase II. A análise estatística dos resultados foi realizada utilizando o programa SPSS (Statistical Package for Social Sciences), adotando o nível de significância de 5 por cento. RESULTADOS: Na fase intermediária, o número de elevações da pata foi significativamente maior nos grupos GF, GM e GFM quando comparados com o grupo GC. CONCLUSÕES: Os resultados sugerem a existência de efeito noradrenérgico e serotoninérgico no sistema inibitório descendente da dor aguda, com a possibilidade de emprego de agonistas serotoninérgicos e α1-adrenérgicos para controle da dor aguda.

BACKGROUND AND OBJECTIVES: There is evidence that the passage of nociceptive information through the posterior horn of the spinal cord (PHSC) on its way to rostral levels of the central nervous system undergoes profound excitatory and inhibitory influences. The objective of the present study was to compare the effects of the subarachnoid administration of methysergide, phentolamine, and phentolamine associated with methysergide on phases I, intermediate, and II of the modified phormaline test in rats. METHODS: Twenty-eight male Wistar rats distributed randomly in four groups (n = 7) to received subarachnoid saline solution (GC), phentolamine (GF), methysergide (GM), or phentolamine associated with methysergide (GFM). Pain was induced by the administration of phormaline in the dorsal region of the right hind paw. The test was divided in three phases: phase I, intermediate, and phase II. Statistical analysis of the results was performed using the software SPSS (Statistical Package for Social Sciences), adopting a level of significance of 5 percent. RESULTS: In the intermediate phase the number of paw elevations was significantly higher in GF, GM, and GFM groups when compared to the GC group. CONCLUSIONS: The results suggest the existence of a noradrenergic and serotonergic effect in the inhibitory descending system of acute pain, with the possibility of using serotonergic and α1-adrenergic antagonists to control acute pain.

JUSTIFICATIVA Y OBJETIVOS: Existen evidencias de que el paso de informaciones nociceptivas por el cuerno posterior de la médula espinal (CPME), y que continúa hacia niveles rostrales del sistema nervioso central, sufre profundas influencias excitatorias e inhibitorias. La presente investigación quiso comparar los efectos de la metisergida, de la fentolamina y de la fentolamina asociada a la metisergida, administrados por vía subaracnoidea, sobre las fases I, intermedia y II del test de la formalina modificado en ratones. MÉTODO: Fueron utilizados en el experimento, 28 ratones Wistar machos, distribuidos aleatoriamente en cuatro grupos (n = 7), para recibir una solución salina (GC), fentolamina (GF), metisergida (GM) o fentolamina asociada a la metisergida ((GFM). El dolor fue inducido por la administración de formalina en la región dorsal de la pata posterior derecha. El test fue dividido en tres fases: fase I, intermedia y fase II. El análisis estadístico de los resultados fue hecho utilizando el programa SPSS (Statistical Package for Social Sciences), [Paquete Estadístico para las Ciencias Sociales], adoptando el nivel de significancia de un 5 por ciento. RESULTADOS: En la fase intermedia, el número de elevaciones de la pata fue significativamente mayor en los grupos GF, GM y GFM cuando se comparó con el grupo GC. CONCLUSIONES: Los resultados nos sugieren la existencia de un efecto noradrenérgico y serotoninérgico en el sistema inhibitorio descendiente del dolor agudo, con la posibilidad del uso de agonistas serotoninérgicos y α1-adrenérgicos para el control del dolor agudo.

Mechanical hypernociception in experimental autoimmune encephalomyelitis / Hipernocicepção mecânica em encefalomielite autoimune experimental

BACKGROUND: Pain is an important clinical manifestation in multiple sclerosis (MS) patients, though it has been neglected in clinical and experimental researches. OBJECTIVE: To investigate the nociceptive response in MOG35-55 experimental autoimmune encephalomyelitis (EAE)-induced mice. METHOD: EAE was induced in 8 to 10 week old C57BL/6 female mice with an emulsion of MOG35-55, Complete Freund Adjuvant, Mycobacterium tuberculosis H37 RA and pertussis toxin. Nociception was evaluated by the von Frey filaments method. A clinical scale ranging from 0 to 15 was used to assess motor impairment. RESULTS: Clinical evidence of disease started at day 10 and peaked at day 14 after immunization. Thereafter, there was no worsening of symptoms until day 26. The EAE-induced mice presented reduced pressure threshold at days 7th and 10th after immunization and before the onset of clinical motor signs. CONCLUSION : The hypernociception found validates MOG35-55 EAE as a model for the study of pain in multiple sclerosis.

INTRODUÇÃO: Dor é uma manifestação importante em pacientes com esclerose múltipla (EM), mas que tem sido negligenciada na pesquisas clínica e experimental. OBJETIVO: Investigar a resposta nociceptiva de camundongos com encefalomielite autoimune experimental (EAE) induzida por MOG35-55. MÉTODO: A EAE foi induzida em camundongos C57BL/6 fêmeas de 8-10 semanas com emulsão contendo MOG35-55, Adjuvante Completo de Freund, Mycobacterium tuberculosis cepa H37 RA e toxina pertussis. A nocicepção foi medida pelo método de filamentos de von Frey. Uma escala clínica variando de 0 a 15 foi utilizada para avaliar a debilidade motora dos animais. RESULTADOS: Os sinais clínicos da doença iniciaram-se no dia 10 e a gravidade máxima foi alcançada no dia 14 após a imunização. Não houve piora dos sintomas até o dia 26. Os camundongos induzidos com EAE apresentaram diminuição do limiar de pressão nos dias 7 e 10 após a imunização e antes do início dos sinais motores. CONCLUSÃO: A hipernocicepção verificada valida a EAE induzida por MOG35-55 como um modelo para estudos de dor em esclerose múltipla.

Streptozotocin-induced mechanical hypernociception is not dependent on hyperglycemia

Since streptozotocin (STZ)-induced diabetes is a widely used model of painful diabetic neuropathy, the aim of the present study was to design a rational protocol to investigate whether the development of mechanical hypernociception induced by STZ depends exclusively on hyperglycemia. Male Wistar rats (180-200 g; N = 6-7 per group) received a single intravenous injection of STZ at three different doses (10, 20, or 40 mg/kg). Only the higher dose (40 mg/kg) induced a significant increase in blood glucose levels, glucose tolerance and deficiency in weight gain. However, all STZ-treated rats (hyperglycemic or not) developed persistent (for at least 20 days) and indistinguishable bilateral mechanical hypernociception that was not prevented by daily insulin treatment (2 IU twice a day, sc). Systemic morphine (2 mg/kg) but not local (intraplantar) morphine treatment (8 µg/paw) significantly inhibited the mechanical hypernociception induced by STZ (10 or 40 mg/kg). In addition, intraplantar injection of STZ at doses that did not cause hyperglycemia (30, 100 or 300 µg/paw) induced ipsilateral mechanical hypernociception for at least 8 h that was inhibited by local and systemic morphine treatment (8 µg/paw or 2 mg/kg, respectively), but not by dexamethasone (1 mg/kg, sc). The results of this study demonstrate that systemic administration of STZ induces mechanical hypernociception that does not depend on hyperglycemia and intraplantar STZ induces mechanical sensitization of primary sensory neurons responsive to local morphine treatment.

Antinociception synergy between the peripheral and spinal sites of the heme oxygenase-carbon monoxide pathway

We have shown that the peripheral and spinal cord heme oxygenase (HO)-carbon monoxide (CO)-soluble guanylate cyclase-cGMP pathways play an important role in antinociception in the rat experimental formalin model. Our objective was to determine if there is synergism between peripheral (paw) and spinal HO-CO pathways in nociception. Rats were handled and adapted to the experimental environment for a few days before the formalin test, in which 50 µL of a 1 percent formalin was injected subcutaneously into the dorsal surface of the right hind paw. The animals were then observed for 1 h and the frequency of flinching behavior was taken to represent the nociceptive response. Thirty minutes before the test, rats were pretreated with intrathecal injections of the HO inhibitor, zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) or heme-lysinate, which is a substrate of the HO pathway. The paw treatments took place 20 min before the test. Low doses of ZnDPBG did not increase nociception, while a low heme-lysinate dose did not change flinching behavior after paw or spinal injections. Combined subactive spinal (50 nmol) and peripheral (40 nmol) low doses of ZnDPBG induced hypernociception (increase of 80 percent in the first and 25 percent in the second phase flinching), whereas combined spinal-peripheral heme-lysinate (50 and 30 nmol) led to second phase antinociception (40 percent reduction in flinching). These findings suggest a synergy between the peripheral and spinal HO-CO pathways. Local activation of the HO system probably regulates the nociception initiation in peripheral tissue and participates in buffering the emerging nociceptive signals at the peripheral and spinal sites of action. In short, an antinociceptive synergy exists between peripheral and spinal HO pathways, which may reduce the doses required and side effects.

Neuroplasticidad y dolor / Neuroplasticity and pain

Todas las formas de dolor incluyen el desarrollo de un estado de hiperalgesia que ilustra la naturaleza dinámica y plástica de la sensación de dolor. La hiperalgesia es la característica más importante del proceso doloroso y es la expresión de la hipersensibilidad de las vías del dolor inducida por la sensibilización de los receptores periféricos que registran eventos dolorosos y de las neuronas que transmiten y procesan esta información sensorial al SNC. Los nociceptores periféricos se sensibilizan adquiriendo una mayor y a veces nueva capacidad de respuesta a los estímulos periféricos. Por otra parte, un proceso de plasticidad sináptica, del cual se ha identificado una variedad de componentes moleculares, interviene en la amplificación central de las señales de las aferencias nociceptivas, lo cual evoca la hipersensibilidad de las neuronas centrales. El resultado final es un proceso sensorial que, a pesar de haber sido puesto en marcha inicialmente por una lesión, puede no mantener una relación estrecha con la lesión original y convertirse en un estado de dolor crónico sin tener una causa definida.

All froms of pain include the development of a hyperalgesic state that illustrates the dynamic and plastic nature of pain sesation. Hyperalgesia is the most prominent feature of the pain process and is the expression of hypersensitivity of the pain pathway induced by the sensitization of the peripheral receptors that signal painful events and of the neurons that transmit and process this sensory information to the CNS. Peripheral nociceptors can be sensitized, acquiring enhanced, and sometimes novel, responsiveness to peripheral stimuli. On the other hand a process of synaptic plasticity, of which several molecular components have already been identified, mediates the central amplification of the afferent signals that leads to the hypersensitivity of central neurons. The final result is a sensory process that, although initially triggered by injury, may not keep a close relationship with the originating injury and develop into a chronic pain state in the absence of a defined cause.

Massaging over the greater occipital nerve reduces the intensity of migraine attacks: evidence for inhibitory trigemino-cervical convergence mechanisms

Activation of the trigemino-cervical system constitutes one of the first steps in the genesis of migraine. The objective of this study was to confirm the presence of trigemino-cervical convergence mechanisms and to establish whether such mechanisms may also be of inhibitory origin. We describe a case of a 39-years-old woman suffering from episodic migraine who showed a significant improvement in her frontal headache during migraine attacks if the greater occipital nerve territory was massaged after the appearance of static mechanical allodynia (cortical sensitization). We review trigemino-cervical convergence and diffuse nociceptive inhibitory control (DNIC) mechanisms and suggest that the convergence mechanisms are not only excitatory but also inhibitory.

Ativação do sistema trigemino-cervical constitui um dos primeiros passos na gênese da crise de migrânea. O objetivo do estudo foi descrever um caso clínico que sugere a existência de mecanismos de convergência trigemino-cervical (CTC) e que esses possam ser do tipo inibitórios. Nós descrevemos o caso de mulher de 39 anos com migrânea episódica que mostrou significante melhora em sua cefaléia frontal durante suas crises quando realizava massagem sobre o território do nervo occipital maior ipsilateral a dor. A melhora clínica só ocorria quando a paciente apresentava alodinia mecânica estática (sensibilização cortical). Neste estudo nós revisamos os conceitos de CTC e de mecanismos de controle inibitório nociceptivo difuso (MCIN), sugerindo que este último é um elemento comprobatório da presença de CTC do tipo inibitório durante as crises de migrânea.

Dolor en el trauma térmico / Pain in thermal trauma

La máxima agresión física que puede sufrir un ser humano son las quemaduras. Actualmente, en Chile se hospitalizan alrededor de 9.000 personas al año por quemaduras, con una tasa de mortalidad que ha ido en disminución en los últimos 20 años, por lo tanto la cantidad de pacientes sobrevivientes va en aumento. La IASP (Internacional Association for Study of Pain) definió el dolor en quemados como: "un dolor agudo y grave, que se produce al sufrir una quemadura y luego continuo con exacerbaciones que declinan gradualmente". El dolor en el trauma térmico está siempre presente, es de intensidad severa y prolongada en el tiempo, con una alta prevalencia de dolor crónico. Se sabe que el aumento en la intensidad se debe a que las quemaduras dañan gran cantidad de nociceptores, produciéndose una amplificación de la respuesta al dolor. Los opioides son el principal pilar en el tratamiento farmacológico. Es fundamental el buen manejo del dolor, para evitar el dolor patológico que aumentará el dolor crónico y con ello el desmedro de la vida personal de nuestros pacientes. Desafortunadamente el subtratamiento es una realidad, produciendo directamente un retraso en la recuperación de sus quemaduras y en la inserción social y laboral.

Burns are the greatest physical aggression that a human being can experience. In Chile, approximately 9000 patients are hospitalized annually due to burns, with a mortality rate that has decreased progressively in the last 20 years, which means that the amount of survivors is increasing. The IASP (International Association for Study of Pain) has defined pain in the burn patient as "an acute and severe pain produced by a burn that later continues with exacerbations that gradually decline". Pain in thermal trauna is always present, of severe intensity and prolonged in time, with a high prevalence of chronic pain. It is Known that the increase in intensity of pain is due to the damage of a great number of nociceptors, that produces an amplification of the response to pain. Opioids are the mainstay of pharmacologic treatment. Appropriate management of pain is fundamental to avoid pathologic pain that will increase the chronic pain and deteriorate the quality of life of our patients. Unfortunately undertreatment is a reality, retarding the healing of the burn wound, and the social and workplace reintegration.

Amygdalar neuronal responses to peripheral nociceptive stimuli in rats.

Amygdala plays a very important role in the mediation of pain. In the present study the behaviour of the amygdalar neurons in response to various peripheral noxious stimuli was observed. Noxious mechanical, thermal, electrical, chemical and the non-noxious stimuli (touch) were applied individually to the animal and then the neuronal responses to these stimuli were recorded. Our results showed that the majority of amygdalar units recorded from medial, lateral and basolateral nuclei, responded to different peripheral noxious (thermal, electrical, chemical mechanical) and non-noxious stimuli by excitation. However few neurons decreased their activity on stimulation. Some of these neurons also exhibited after discharge following application of higher intensity of noxious stimuli.

Ventricular nociception induced vesicular motility and urine flow: their relationship.

Heart acts as an important reflexogenic organ. Reflex urination and defaecation are two of the most important visceral symptoms observed in patients with myocardial ischaemia, infarction etc. In experimental animals also ventricular nociceptor stimulation by left anterior descending coronary artery (LAD) occlusion and nicotine application causes biphasic changes in urinary bladder movement and urine flow. Aim of the present study is to elucidate if there is any correlation between urine formation by the kidneys and movement of the urinary ladder under such experimental conditions. The experiments performed on intact cats show apparent coincidence of the two events. But, subsequent experiments following denervation of vagi and inferior cardiac nerve (ICN), spinal transaction and decerebration experiments indicate that these two are separate events. Further, experiments with different neurotransmitter blockers indicate that ventricular nocieptor induced urine formation and urinary bladder movements are two separate reflex responses and not dependent on each other.

Utilizaçäo da algometria de pressäo na determinaçäo dos limiares de percepçäo dolorosa trigeminal em voluntários sadios: um novo protocolo de estudos / Using algometry of pressure measuring the threshold of trigeminal pain perception in normal volunteers: a new protocol of studies

Algometria de pressäo é uma técnica que mensura a fisiologia do sistema nociceptivo. Atuando diretamente sobre os nociceptores periféricos responsívos aos estímulos pressóricos esta técnica permite o estudo da integridade nociceptiva em indivíduos normais ou portadores de diferentes síndromes álgicas. Foram testados 29 voluntários assintomáticos em que pesquisamos os limiares de percepçäo dolorosa, mensurando-os de forma direta sobre a emergência dos nervos supra-orbital, infra-orbital, mental. Registramos os seguintes valores médios algométricos: nervo mental direito 46,2 Kg/cm² e esquerdo 48,6 Kg/cm²; nervo supra-orbital direito 47,7 Kg/cm² e esquerdo 45,2 Kg/cm²; nervo infra-orbital direito 53,9 Kg/cm² e esquerdo 55,4 Kg/cm². Após revisäo dos princípios de utilizaçäo da algometria, validamos este protocolo apresentando os valores médios obtidos pela mensuraçäo do sistema trigeminal comparando-os posteriormente com uma regiäo inervada pelos primeiros ramos cervicais (nervo occipital maior) e regiäo do músculo temporal

Dolor orofacial: Características. Neurofisiología: mecanismos moduladores. Su vinculación con alteraciones del movimiento mandibular / Orofacial pain: Characteristics. Neurophysiology: modulating mechanisms. Its association with mandibular movement alterations

El dolor es el síntoma más habitual en la consulta odontológica y el factor causal de mayor importancia y frecuencia para que el paciente acuda en busca de asistencia. En los últimos años los neurólogos han hecho importantes avances en el estudio de los aspectos neurofisiológicos del dolor, referidos fundamentalmente a los mecanismos y sustancias que regulan su persistencia e intensidad. Lamentablemente gran parte de la información llega muy escasamente al odontólogo. Es interesante señalar también que tanto en el nivel pregrado como en el de posgrado son muy escasos los cursos con contenidos referidos a este tema. El objetivo de este trabajo es brindar una revisión básica y actualizada sobre distintos aspectos del síntoma dolor, a saber: nocicepción y dolor, diferencias conceptuales. Características: tipo de dolor: crónico-agudo, superficial, heterotópico. Neurofisiología: vías de conducción. Mecanismos modulares inhibitorios y de sensibilización, metaméricos y centrales. Sustancias que lo provocan: fenómenos de hiperalgesia, neuroplasticidad y persistencia del síntoma. Características del dolor inflamatorio, sensibilización periférica. El factor psicológico como modulador intrínseco del dolor vinculado al sufrimiento. Aspectos cognitivos, afectivo-emocionales y conductuales. Por último, algunos conceptos referidos a la posible asociación del dolor con alteraciones del movimiento mandibular

Adrenergic sensitivity of uninjured C-fiber nociceptors in neuropathic rats

We investigated the adrenergic sensitivity of afferent fibers in the L4 dorsal roots of rats with a unilateral ligation of the L5-L6 spinal nerves. About 12% of nociceptive fibers on the affected side were excited by sympathetic stimulation or by intra-arterial injection of norepinephrine which did not affect A beta-fiber activity. Sympathetic excitation of nociceptive fibers was suppressed by alpha 1-antagonist prazosin, while it was unaffected by alpha 2-antagonist yohimbine. Most of these fibers were excited by intra-arterial injection of alpha 1-agonist phenylephrine, without being affected by an injection of alpha 2-agonist clonidine. Sympathetic excitation was blocked by lidocaine applied near the receptive fields of recorded fibers. The results suggested that some nociceptors remaining intact after partial nerve injury become sensitive to sympathetic activity by the mediation of alpha 1-adrenoceptors in the peripheral endings.

Hypothalamo-limbic involvement in modulation of tooth-pump stimulation evoked nociceptive response in rats.

The hypothalamo-limbic system has been implicated in recognizing the affective significance of pain and elicitation of related emotional responses. Several evidences from different studies support a role of these areas in endogenous analgesic mechanisms for pain modulation as elucidated by different pain tests in more than one animal model. In the above context, the aim of this study was to investigate the relative effectiveness of the pain modulatory action of hypothalamic and limbic structures in rat using similar stimulation parameters, and studying the effect on tooth pulp stimulation evoked jaw opening reflex (TP-JOR). To achieve the objective, unilateral stimulation of hypothalamic (lateral = LH; ventromedial = VMN; anterior = AH) and limbic areas (amygdala = AMYG; hippocampus = HIPP) was done on the TP-JOR test. A significant reduction in the amplitude of EMG recorded from the digastric muscle (dEMG) as a result of tooth-pulp stimulation was observed on stimulation of LH, VMN, AMYG and HIPP but not from AH. Also, the magnitude of this effect was almost similar from these areas. The results suggest that these areas (except AH) have an antinociceptive role in tooth-pulp stimulation evoked pain response.