Anti-hyperalgesic effect of electroacupuncture in a model of post-incisional pain in rats

Electroacupuncture has been proposed to be a low cost and practical method that allows effective pain management with minimal collateral effects. In this study we have examined the effect of electroacupuncture against the hyperalgesia developed in a model of post-incisional pain in rats. A 1-cm longitudinal incision was made through the skin and fascia of the plantar region of the animal hind paw. Mechanical hyperalgesia in the incision was evaluated 135 min after the surgery with von Frey filaments. The tension threshold was reduced from 75 g (upper limit of the test) to 1.36 ± 0.36 g (mean ± SEM) in control rats. It is shown that a 15-min period of electroacupuncture applied 120 min after surgery to the Zusanli (ST36) and Sanyinjiao (SP6) points, but not to non-acupoints, produces a significant and long-lasting reduction of the mechanical hyperalgesia induced by the surgical incision of the plantar surface of the ipsilateral hind paw. The tension threshold was reduced from 75 to 27.6 ± 4.2 g in animals soon after the end of electroacupuncture. The mechanical threshold in this group was about 64% less than in control. Electroacupuncture was ineffective in rats treated 10 min earlier with naloxone (1 mg/kg, ip), thus confirming the involvement of opioid mechanisms in the antinociceptive effects of such procedure. The results indicate that post-incisional pain is a useful model for studying the anti-hyperalgesic properties of electroacupuncture in laboratory animals.

Endogenous opiate analgesia induced by tonic immobility in guinea pigs

A function of the endogenous analgesic system is to prevent recuperative behaviors generated by tissue damage, thus preventing the emission of species-specific defensive behaviors. Activation of intrinsic nociception is fundamental for the maintenance of the behavioral strategy adopted. Tonic immobility (TI) is an inborn defensive behavior characterized by a temporary state of profound and reversible motor inhibition elicited by some forms of physical restraint. We studied the effect of TI behavior on nociception produced by the formalin and hot-plate tests in guinea pigs. The induction of TI produced a significant decrease in the number of flinches (18 ± 6 and 2 ± 1 in phases 1 and 2) and lickings (6 ± 2 and 1 ± 1 in phases 1 and 2) in the formalin test when compared with control (75 ± 13 and 22 ± 6 flinches in phases 1 and 2; 28 ± 7 and 17 ± 7 lickings in phases 1 and 2). In the hot-plate test our results also showed antinociceptive effects of TI, with an increase in the index of analgesia 30 and 45 min after the induction of TI (0.67 ± 0.1 and 0.53 ± 0.13, respectively) when compared with control (-0.10 ± 0.08 at 30 min and -0.09 ± 0.09 at 45 min). These effects were reversed by pretreatment with naloxone (1 mg/kg, ip), suggesting that the hypoalgesia observed after induction of TI behavior, as evaluated by the algesimetric formalin and hot-plate tests, is due to activation of endogenous analgesic mechanisms involving opioid synapses.

Rôle et implication du système cannabinoïde dans la modulation périphérique de la douleur inflammatoire et neuropathique

Les dérivés de l’opium (opioïdes) et du cannabis (cannabinoïdes) présentent de nombreuses propriétés intéressantes. Suite à l’identification de leurs récepteurs respectifs, diverses stratégies pharmacologiques ont tenté d’exploiter leurs propriétés analgésiques. Le clonage des récepteurs cannabinoïdes CB1 et CB2 a favorisé la découverte de composés endogènes pour ces récepteurs, les endocannabinoïdes, dont les deux plus étudiés sont l’anandamide et le 2-arachidonyl glycérol (2-AG). Cette découverte a également mené à l’identification d’enzymes qui catalysent l’inactivation de ces cannabinoïdes endogènes : une amidohydrolase des acides gras ou FAAH ainsi qu’une monoacylglycérol lipase ou MAGL. Le système cannabinoïde endogène est régulé à la hausse dans une variété de processus pathologiques, tels que les douleurs inflammatoire et neuropathique. Cette augmentation est habituellement interprétée comme une réaction physiologique visant à rétablir l’homéostasie et elle a notamment été observée en périphérie. Les endocannabinoïdes semblent donc agir de façon spécifique à des moments clés dans certains tissus ciblés afin de minimiser les conséquences reliées au déclenchement de ces douleurs. Cette observation est très intéressante d’un point de vue thérapeutique puisqu’elle suggère la possibilité de cibler les enzymes de dégradation des endocannabinoïdes dans le but d’augmenter leurs concentrations locales et d’ainsi prolonger leur action neuromodulatrice. En périphérie, l’activation des récepteurs cannabinoïdes induit des effets antinociceptifs bénéfiques tout en minimisant les effets indésirables souvent associés à leur activation centrale. Nous avons orienté nos travaux vers la modulation périphérique de ce système endogène à l’aide d’inhibiteurs des enzymes de dégradation des endocannabinoïdes afin d’évaluer leur potentiel thérapeutique et d’élucider les mécanismes d’action qui sous-tendent leurs effets dans des modèles animaux de douleurs inflammatoire et neuropathique. Nous avons démontré que cette approche permet de soulager les symptômes associés à ces deux types de douleurs, et ce via les récepteurs CB1 et CB2. Les systèmes cannabinoïde et opioïde présentent des similitudes, dont des localisations similaires le long des voies de la douleur, des mécanismes d’action relayés par des récepteurs couplés aux protéines G et des propriétés pharmacologiques communes telles que l’analgésie. Le système opioïde est impliqué dans les effets antinociceptifs induits par les cannabinoïdes. À l’inverse, le rôle joué par le système cannabinoïde dans ceux induits par la morphine demeure incertain. Nous avons démontré que les effets antinociceptifs périphériques et spinaux produits par la morphine sont diminués chez les souris génétiquement modifiées chez lesquelles l’expression des récepteurs CB1 ou CB2 a été éliminée, laissant supposer un rôle pour ces récepteurs dans les effets de la morphine. Nous avons de plus démontré que la diminution de l'analgésie produite par la morphine dans ces souris n'est pas causée par un dysfonctionnement des récepteurs opioïdes mu (MOP) ni par une régulation à la baisse de ces récepteurs. Nos résultats confirment l'existence d'interactions fonctionnelles entre les systèmes cannabinoïde et opioïde au niveau périphérique et spinal. Ces observations sont prometteuses d’un point de vue thérapeutique puisqu’une modulation périphérique ciblée des niveaux d’endocannabinoïdes et d’opioïdes endogènes permettrait de produire des effets analgésiques bénéfiques potentiellement synergiques tout en minimisant les effets indésirables associés à l’activation centrale de ces systèmes.

Efeitos antinociceptivos e sedativos da buprenorfina, da acepromazina ou da associação buprenorfina e acepromazina em gatos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of the analgesic and antiedematogenic activities of Quassia amara bark extract

We evaluated the possible antiedematogenic, antinociceptive and/or sedative effects of four different extracts obtained from the bark of Quassia amara namely, 70% ethanol (70EtOH), 100% ethanol (100EtOH), dichloromethane (DCM) and hexane extracts (HEX). The oral administration (100, 250 and 500 mg/kg) of these extracts did not show significant effects in any experiment. However, when administered intraperitoneally, the HEX extract decreased the paw edema induced by carrageenan, showed antinociceptive effects on the hot-plate test and on acetic acid-induced writhing, and showed sedative effects on pentobarbital-induced sleep. Naloxone did not reverse the antinociceptive effect of this extract. In conclusion, although the mechanisms are uncertain, the results demonstrated that these effects are apparently related to sedative and muscle relaxant or psychomimetic activities of the HEX extract of the plant. (C) 2002 Elsevier B.V. Ireland Ltd. All rights reserved.

Efeito do tratamento com algumas vitaminas B na potencializaçã o do efeito antiinflamatório e antinociceptivo do diclofenaco e da talidomida

The effects of some B vitamins on chemical nociception in mice or paw edema in rats were investigated. A combination of thiamine (B1), pyridoxine (B6) and cyanocobalamin (B12), in doses of 100,100 and 5mg/kg, i.p., respectively, potentiated the inhibition by diclofenac or thalidomide of paw edema induced by carrageenin in rat. Antinociceptive effects of diclofenac and thalidomide inhibition of abdominal contortion were also potentiated by the combination of the vitamins B1, B6 and B12. Thiamine, pyridoxine and cyanocobalamin given singly were effective in potentiating antinociceptive effects of thalidomide, but only cyanocobalamin potentiated these effects of diclofenac, probably reflecting the differing mechanisms of action of the two drugs. The results document the positive influence of B vitamins on antinociceptive effects of diclofenac or thalidomide and support the use of B vitamins to shorten the treatment time and reduce the daily dose of anti-inflammatories.

Potencialização do efeito antiinflamatório e antinociceptivo do diclofenaco e da nimesulida por vitaminas do complexo B

The effects of a combination of some B vitamins and diclofenac or nimesulide on chemical nociception in mice or paw edema in rats were investigated. While the vitamins alone had no effect, combination of thiamine (B1), pyridoxine (B6) and cyanocobalamin (B12), given i.p. in doses of 100mg and 5mg/kg, respectively, potentiated the inhibition by nimesulide (5mg/kg) of paw edema induced by carrageenin in rats. Antinociceptive effects of diclofenac and nimesulide (inhibition of abdominal writhing induced by acetic acid in mice) were also potentiated by the combination of the vitamins B1, B6 and B12. Thiamine, pyridoxine and cyanocobalamin given singly were effective in potentiating antinociceptive effects of nimesulide, but only cyanocobalamin potentiated these effects of diclofenac, probably reflecting the differing mechanisms of action of the two drugs. The results document the positive influence of B vitamins on the antinociceptive effects of diclofenac or nimesulide and support the use of B vitamins to shorten the treatment time and reduce the daily dose of anti-inflammatories.

Efeitos das injeções epidurais de amitraz ou xilazina em vacas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos comportamental, clínico e antinociceptivo da crotalfina em eqüinos: comparação com morfina, U50-488H e fenilbutazona

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Propriedades químicas e farmacológica da apocinina, vanilina e ácido vanílico

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB

Efeitos antinociceptivos dose-resposta e de diferentes vias de administração da buprenorfina em felinos domésticos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Papel dos mecanismos mediados pelo fator de liberação de corticotrofina e pelo complexo receptor N-Metil-D-Aspartato-Óxido Nítrico nas reações associadas a estímulos aversivos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

A farmacocinética da metadona e seus efeitos antinociceptivos, comportamentais e sobre a concentração alveolar mínima de sevofluorano em felinos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Investigação da participação de adrenoceptores α1 no efeito antinociceptivo da amitriptilina em um modelo de dor neuropática

Tricyclic antidepressants, such as amitriptyline, are inhibitors of serotonin and norepinephrine neuronal reuptake and this action has been implied in changes in pain threshold supporting its use to alleviate neuropathic pain. Although is known that 1 adrenoceptors participate in the antinociceptive effect of amitriptyline it is unclear which receptor subtype is the target for the increased synaptic levels of norepinephrine resultant from the inhibition of neuronal uptake. Paradoxically, several tricyclic antidepressants including amitriptyline also behave as antagonists of 1 adrenoceptors with different affinities for its subtypes: these drugs have 10 to 100-fold higher affinities for 1A than for 1B and 1D adrenoceptors. This work investigated the involvement of 1 adrenoceptors subtypes in the antinociceptive effect of the amitriptyline in a constriction of the sciatic nerve in rats by determining the effects of subtype selective 1 adrenoceptors antagonists. Fifteen days later, mechanical hyperalgesia was analyzed in a Randall-Selitto test. The 1A-selective antagonist RS100329 was the most potent antagonist of the contractions of the rat prostate, whereas the 1D-selective antagonist BMY 7378 (up to 100g/Kg) was unable to affect these contractions. The antagonist prazosin, BMY 7378 and 5-methyl urapidil inhibited the antinociceptive effect of the amitriptyline. However, the highly selective 1A adrenoceptor antagonist RS100329 was unable to affect the antinociception induced by amitriptyline. These results point out that 1B and/or 1D adrenoceptors, but not 1A, are involved in the antinociceptive effects of amitriptyline

Validação de métodos nociceptivos elétrico, mecânico e térmico para avaliação de dor de equinos tratados com metadona associada à detomidinaou acepromazina

Pós-graduação em Anestesiologia - FMB