Involvement of Opioid Peptides in the Analgesic Effect of Spinal Cord Stimulation in a Rat Model of Neuropathic Pain / 神经科学通报·英文版

Spinal cord stimulation (SCS)-induced analgesia was characterized, and its underlying mechanisms were examined in a spared nerve injury model of neuropathic pain in rats. The analgesic effect of SCS with moderate mechanical hypersensitivity was increased with increasing stimulation intensity between the 20% and 80% motor thresholds. Various frequencies (2, 15, 50, 100, 10000 Hz, and 2/100 Hz dense-dispersed) of SCS were similarly effective. SCS-induced analgesia was maintained without tolerance within 24 h of continuous stimulation. SCS at 2 Hz significantly increased methionine enkephalin content in the cerebrospinal fluid. The analgesic effect of 2 Hz was abolished by μ or κ opioid receptor antagonist. The effect of 100 Hz was prevented by a κ antagonist, and that of 10 kHz was blocked by any of the μ, δ, or κ receptor antagonists, suggesting that the analgesic effect of SCS at different frequencies is mediated by different endorphins and opioid receptors.

Do opioid receptors play a role in the pathogenesis of the inflammatory response in acute pancreatitis? / Os receptores opioides desempenham papel na patogênese da resposta inflamatória na pancreatite aguda?

PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.

OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda.

Participation of endogenous opioids in the antinociception induced by resistance exercise in rats

Exercise is a low-cost intervention that promotes health and contributes to the maintenance of the quality of life. The present study was designed to investigate the influence of different resistance exercise protocols on the nociceptive threshold of rats. Female Wistar rats were used to perform exercises in a weight-lifting exercise model. The following groups were examined (N = 6 per group): untrained rats (control group); an acute protocol group consisting of rats submitted to 15 sets of 15 repetitions of resistance exercise (acute group); rats exercised with 3 sets of 10 repetitions, three times per week for 12 weeks (trained group), and a group consisting of trained rats that were further submitted to the acute protocol (trained-acute group). The nociceptive threshold was measured by the paw-withdrawal test, in which the withdrawal threshold (escape reaction) was measured by an apparatus applying force to the plantar surface of the animal paw. The opioid antagonist naloxone (2 mg/kg) was administered subcutaneously 10 min before the exercise protocols. The trained group demonstrated antinociception only up to day 45 of the 12-week training period. A significant increase (37 percent, P < 0.05) in the nociceptive threshold was produced immediately after exercise, decreasing to 15 percent after 15 min, when the acute exercise protocol was used. Naloxone reversed this effect. These data show that the acute resistance exercise protocol was effective in producing antinociception for 15 min. This antinociceptive effect is mediated by the activation of opioid receptors.

Opioidergic orofacial antinociception induced by electroacupuncture at acupoint St36

The participation of opioids in the antinociceptive effect of electroacupuncture was evaluated in terms of nociception produced by thermal stimuli applied to the face of male Wistar rats, weighing 180-230 g. Electrical stimulation (bipolar and asymmetric square wave with 0.5 mA intensity for 20 min) of acupoint St36, located in the anterior tibial muscle 10 mm distal to the knee joint, induced antinociception in the present model, which was maintained for 150 min. Acupoint LI4, located in the junction of the first and second metacarpal bones, did not achieve antinociception at any frequency studied (5 Hz: 1.7 ± 0.1; 30 Hz: 1.8 ± 0.1; 100 Hz: 1.7 ± 0.1 vs 1.4 ± 0.2). The antinociception obtained by stimulation of acupoint St36 was only achieved when high frequency 100 Hz (3.0 ± 0.2 vs 1.0 ± 0.1) was used, and not with 5 or 30 Hz (1.2 ± 0.2 and 0.7 ± 0.1 vs 1.0 ± 0.1). The antinociceptive effect of acupuncture occurred by opioid pathway activation, since naloxone (1 and 2 mg/kg, subcutaneously) antagonized it (1.8 ± 0.2 and 1.7 ± 0.2 vs 3.0 ± 0.1).

Posibles mecanismos de la eficacia o falta de eficacia de los compuestos opiodes sobre el dolor crónico por deaferentación / Possible mechanisms of the efficacy or non efficacy of the opioid compounds about chronic pain by deafferentation

El dolor crónico por deaferentación constituye un problema clínico que se caracteriza por su persistencia y resistencia a mejorar con cualquiera de los analgésicos y neuromoduladores actuales. Una de las principales controversias en el tratamiento del dolor crónico por deaferentación es el uso de los opioides. Por este motivo, en esta revisión se hace un Análisis sobre la historia de los compuestos opioides, de los péptidos opioides endógenos y de sus receptores, así como de los aspectos bioquímicos en la patología del dolor crónico por deaferentación periférico y central relacionados con la plasticidad neuronal e involucrados en la alodinia e hiperalgesia y la interacción de los compuestos opioides con el N-metil-D-aspartato (NMDA), la proteína cinasa C (CPK) y el óxido nítrico en la tolerancia a la morfina. Con el conocimiento de los eventos bioquímicos a nivel experimental se han iniciado las opciones farmacológicas en el tratamiento del dolor crónico y en un futuro aparecer nuevos fármacos que actualmente existen en experimentación, los antagonistas NMDA (MK81 y LY274614), el antagonista de la CPK (gangliósido GM1) y el inhibidor de la enzima de la síntesis de óxido nítrico NOARG.

Estudo do comportamento motor decorrente da ingestäo de leite, em fetos de ratos: revisäo de literatura / Study of the motor behavior decurrent of the ingestion of milk in rat fetuses: review of literature

Nesta revisäo, focou-se os comportamentos motores e respostas fisiológicas de animais neonatos, associados com a ingestäo ou infusäo de leite, estudados em experimentos expressivos. Os experimentos demonstraram que os comportamentos e respostas foram mediados por neurotransmissores liberados, simultaneamente, à estimulaçäo com leite. Os experimentos säo apresentados detalhadamente com o objetivo de fornecer ao leitor uma visäo clara do desenvolvimento atual dos processos experimentais dessa linha de pesquisa.

Sistema nervioso autónomo y estres gástrico, en ratas / Autonomic nervous system and gastric stress in rats

En grupos diferentes de ratas Wistar (n=10), se estudió el efecto fisiopatológico del sistema nervioso autónomo en el estrés gástrico, en el modelo experimental de estrés, por inmovilización e inmersión en agua a 15 grados Celsius durante 6 hs., en el que se tabuló el por ciento lesional macroscópica de la mucosa gástrica y en sangre se midió el cortisol, malatonina, nor-adrenalina, adrenalina, dopamina y serotonina. En estrés testigo se encontró un área necrótica gástrica de un 80 por ciento en sangre solo se halló aumento de nor-adrenalina y adrenalina. Se estudiaron fármacos en dosis dependientes, agonistas y antagonistas de los receptores Beta adrenérgicos, antagonistas alpha adrenérgicos postinápticos; colinérgicos y anticolinérgicos, de los receptores endorfínicos y de los GABA. Se encontró que Isoproterenal, Prazosim, Doxazosina, Tramadol y Vgabatrin dieron marcada protección de la mucosa gástrica en el estrés, con un área necrótica cercana al 0 por ciento (P<0.001); en contraste, Propanolol, Acetilcolina, Atropina, Naloxona y Flumazenil no se diferenciaron del estrés testigo (P>0.5). Todos los fármacos estudiados dieron similares aminas vasoactivas que el estrés testigo. Se concluyó que el sistema nervioso autónomo en su vinculado a sus receptores con incremento de la microcirculación esplácnica.

Receptores opioides a la luz de la biología molecular: explican mas de 6.000 años de farmacología empírica / Opioid receptors in the era of molecular biology: explain more than 6.000 years of empiric pharmacology

The medicinal use of opium and of morphine in different cultures and ancient civilizations is described. Research within the past 40 years have demonstrated the existence of brain opiate receptors. Morphine and related opioid analgetic interact at these sites in the nervous system to produce the characteristic pharmacological effects of these drugs. The opiate receptors have structural homologies with a variety of other cell membrane recpetors; they activate second messenger-based chemical transduction systems in the cell embrane and are endowed with several regulation mechanisms. These opiate receptors are presumably activated under specific physiological conditions by endogenous ligands (opiopeptins). It is currently thought thar morphine mimicks the opiopeptins by interacting with these receptors either at different molecular subsites or with a different mode of action

use of specific opioid receptor antagonist [nalthrexone] in hypertensive pregnancy

Twenty pregnant patients induced hypertension in late pregnancy [30-36 weeks] were randomly allocated to either Nalthrexone [R Trexan], specific opioid receptor antagonist, or placebo treatment. Nalthrexone was given in the form of tablets, 50 mg/12 hours. Blood pressure was measured twice daily and measuring of proteinunria was done daily with observation of edema of the lower limbs. The serum levels of prolactin before, one week and 2 weeks after treatment, were measured by radioimmunoassay. This was done also to 51 normal pregnant women in the same gestational age. The results show normalization of blood pressure, subsidence of pretibial edema and minimal decrease in body weight. This was associated with decrease of serum proloctin from 148 +/- 12.8 to 23.4 +/- 4.76 ng/ml after treatment. All babies were delivered at term in a healthy condition. There was no effect on the initiation of lactation which was normal up to 3 months after delivery. The present results of potential value from the clinical and biological points of view are: Nalthrexone is an effective and safe drug to be used in PIH. Beta-endorphin may play a role in the pathogenesis of PIH through controlling the release of prolactin

Interaction between cholinergic and opiate receptors of the lateral hypothalamus in the control of renal excretion in rats

The present study was carried out to investigate the participation and interaction between cholinergic and opiate receptors of the lateral hypothalamus (LH) in the regulation of Na+, K+ and water excretion. Malew Holtzman rats were implanted with chronic cerebral cannulas into the LH. Urine was collected over a period of 2h after injection of carbachol, FK-33824 + carbachol or naloxone + carbachol into the LH. Carbachol (8nmol) reduced urinary volume and increased Na + excretion. Previous injection of FK-333824(100ng) into the LH increased the antidiuretic effect of carbachol, but blocked the increase in Na+ excretion and decreased K+ excretion. Naloxone. Naloxone (10microng) produced no changes in the effect of carbacho9l on renal excretion. These data show an inhibitory effect of opiate receptors on the changes in urinary Na+ and K+ excretion that are induced by chronergic stimulation of the LH in rats, and a potentiating effect on antidiuresis

Effect of bilateral caudatal lesion on pain threshold in rats.

Pain threshold was determined in eleven adult male rats (Haffkine strain) on electrical stimulation of midpart of tail. Three responses, namely tail withdrawal, vocalization and vocalization afterdischarge were studied. Of these eleven animals, seven in experimental group were subjected to bilateral electrolytic lesion of mid-dorsal caudate nucleus while remaining four animals were sham operated. The increase in pain threshold after caudatal destruction for all the three responses suggests the possible modulatory role of mid-dorsal caudate nucleus in the mechanism of pain.

New Frontiers in Pharmacology

No abstract available.