RESUMO
The pro-resolving mechanism is a recently described endogenous process that controls inflammation. The present study evaluated components of this mechanism, including annexin 1 (ANXA1) and the formyl peptide receptor 2/ALX (FPR2/ALX) receptor, in the antihyperalgesic effect induced by electroacupuncture (EA) in an animal model of persistent peripheral inflammation. Male Swiss mice underwent intraplantar (i.pl.) injection with complete Freund's adjuvant (CFA). Mechanical hyperalgesia was assessed with von Frey monofilaments. Animals were treated with EA (2-10 Hz, ST36-SP6) or subcutaneous BML-111 injection (FPR2/ALX agonist) for 5 consecutive days. In a separate set of experiments, on the first and fifth days after CFA injection, animals received i.pl. WRW4 (FPR2/ALX antagonist) or naloxone (non-selective opioid receptor antagonist) before EA or BML-111 injection. Paw protein levels of FPR2/ALX and ANXA1 were evaluated on the second day after CFA injection by western blotting technique. EA and BML-111 reduced mechanical hyperalgesia. I.pl. naloxone or WRW4 prevented the antihyperalgesic effect induced by either EA or BML-111. EA increased ANXA1 but did not alter FPR2/ALX receptor levels in the paw. Furthermore, i.pl. pretreatment with WRW4 prevented the increase of ANXA1 levels induced by EA. This work demonstrates that the EA antihyperalgesic effect on inflammatory pain involves the ANXA1/FPR2/ALX pro-resolution pathway. This effect appears to be triggered by the activation of FPR2/ALX receptors and crosstalk communication with the opioid system.
Assuntos
Anexina A1/metabolismo , Eletroacupuntura/métodos , Hiperalgesia/terapia , Dor Nociceptiva/terapia , Receptores de Formil Peptídeo/metabolismo , Receptores Opioides/metabolismo , Animais , Adjuvante de Freund/toxicidade , Ácidos Heptanoicos/farmacologia , Hiperalgesia/etiologia , Hiperalgesia/metabolismo , Masculino , Camundongos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Nociceptividade/efeitos dos fármacos , Dor Nociceptiva/etiologia , Dor Nociceptiva/metabolismo , Receptores de Formil Peptídeo/antagonistas & inibidores , Receptores Opioides/uso terapêuticoRESUMO
Pain is a normal protective response to tissue injury caused by physical trauma, noxious chemicals and microbiological agents. Use of chemical drugs and medicinal plants is a conventional method to manage pain; however, their side effects have caused increased tendency to the use of herbal medicines among patients. This study was conducted to investigate antinociceptive action of Ricinus communis seeds extract (RCE) in male Balb/C mice. In this experimental study, 72 male mice weighing 25-35gr were used. Animals were randomly divided into six groups of 12 mice each, including: Control group, three groups separately treated respectively with 100, 200, and 400mg/kg hydroethanolic R. communis seed extract, morphine (1mg/kg)-treated group, and naloxone (0.1mg/kg) + R. communis seed extract (200mg/kg)-treated group. All animals received extract and drugs intraperitoneally. To evaluate the analgesic effect of the extract, writhing and tail flick tests were used. The 200 and 400mg/kg of the extract significantly increased pain threshold compared to the control group in writhing and tail flick tests (P<0.01). Moreover, 400mg/kg of the extract showed a stronger antinociceptive effect especially in writhing test compared to the control and other treated groups (P<0.001). Analgesic effects of hydroethanolic R. communis seed extract observed in the tail flick and writhing tests are probably related to activation of opioid system. Results may suggest that this plant extract might be beneficial in relieving human pain.(AU)
A dor é um sentido com efeitos essencialmente protetores. Ouso de drogas químicas e plantas medicinais é um método convencional para gerenciar a dor, no entanto, seus efeitos colaterais têm causado uma maior tendência para o uso de ervas medicamentosas entre os pacientes. Este estudo nos levou a investigar as ações antinociceptivas do extrato de sementes de Ricinus communis (RCE) em camundongos machos. Neste estudo experimental, foram utilizados 72 camundongos machos com peso de 25±30gr. Os animais foram divididos aleatoriamente em seis grupos de 12 cada: grupo controle, três grupos tratados separadamente com 100, 200 e 400mg/kg de extrato de sementes de R. communis hidroetanolico, grupo tratado com morfina (1mg/kg) e naloxona (0,1mg/kg) + R. Grupo tratado com extrato de semente de communis (200mg/kg). Para avaliar o efeito analgésico do extrato, utilizaram-se testes de contorção e cauda. Os dados foram analisados pela ANOVA e pelo teste de Tukey. P<0,05 foi considerado estatisticamente significante. Dose de 200 e 400mg/kg de extrato aumentou significativamente o limite de dor em comparação com o grupo controle em testes de retorção e cauda (P<0,01). Além disso, 400mg/kg de extracto apresentaram efeito antinoceptivo mais forte especialmente no teste de contorção em comparação com o controle e outros grupos tratados (P <0,001). Os efeitos analgésicos do extrato de semente de R. communanolanol foram observados no teste da cauda e nos testes de contorção. Este efeito provavelmente está relacionado à ativação do sistema opioide.(AU)
Assuntos
Animais , Masculino , Ratos , Dor Nociceptiva/terapia , Dor Nociceptiva/veterinária , Analgésicos/análise , Ricinus/química , Extratos Vegetais/uso terapêutico , SementesRESUMO
Cortical electrical stimulation (CES) has shown to be an effective therapeutic alternative for neuropathic pain refractory to pharmacological treatment. The primary motor cortex(M1) was the main cortical target used in the vast majority of both invasive and non-invasive studies. Despite positive results M1-based approaches still fail to relieve pain in a significant proportion of individuals. It has been advocated that the direct stimulation of cortical areas directly implicated in the central integration of pain could increase the efficacy of analgesic brain stimulation. Here, we evaluated the behavioral effects of electrical stimulation of the insular cortex (ESI) on pain sensitivity in an experimental rat model of peripheral neuropathy, and have described the pathways involved. Animals underwent chronic constriction of the sciatic nerve in the right hind limb and had concentric electrodes implanted in the posterior dysranular insular cortex. Mechanical nociception responses were evaluated before and at the end of a 15-min session of ESI (60Hz, 210µs, 1V). ESI reversed mechanical hypersensitivity in the paw contralateral to the brain hemisphere stimulated, without inducing motor impairment in the open-field test. Pharmacological blockade of µ-opioid (MOR) or type 1-cannabinoid receptors (CB1R) abolished ESI-induced antinociceptive effects. Evaluation of CB1R and MOR spatial expression demonstrated differential modulation of CB1R and MOR in the periaqueductal gray matter (PAG) of ESI-treated rats in sub-areas involved in pain processing/modulation. These results indicate that ESI induces antinociception by functionally modulating opioid and cannabinoid systems in the PAG pain circuitry in rats with experimentally induced neuropathic pain.
Assuntos
Córtex Cerebral/fisiopatologia , Dor Crônica/fisiopatologia , Dor Crônica/terapia , Estimulação Encefálica Profunda , Doenças do Sistema Nervoso Periférico/fisiopatologia , Doenças do Sistema Nervoso Periférico/terapia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Dor Nociceptiva/fisiopatologia , Dor Nociceptiva/terapia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Substância Cinzenta Periaquedutal/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide/antagonistas & inibidores , Receptor CB1 de Canabinoide/metabolismo , Receptores Opioides mu/antagonistas & inibidores , Receptores Opioides mu/metabolismo , Antagonistas da Serotonina/farmacologia , TatoRESUMO
Transcutaneous electrical nerve stimulation (TENS) is a non-pharmacological therapy for the treatment of pain. The present work investigated the effect of cannabidiol, naloxone and diazepam in combination with 10 Hz and 150 Hz TENS. Male Wistar rats were submitted to the tail-flick test (baseline), and each rodent received an acute administration (intraperitoneal) of naloxone (3.0mg/kg), diazepam (1.5mg/kg) or cannabidiol (0.75 mg/kg, 1.5mg/kg, 3.0mg/kg, 4.5mg/kg, 6.0mg/kg and 12.0mg/kg); 10 min after the acute administration, 10 Hz or 150 Hz TENS or a sham procedure was performed for 30 min. Subsequently, tail-flick measures were recorded over a 90-min period, at 5-min intervals. 10 Hz TENS increased the nociceptive threshold during the 90-min period. This antinociceptive effect was reversed by naloxone pre-treatment, was not altered by diazepam pre-treatment and was abolished by cannabidiol pre-treatment (1.5mg/kg). Moreover, 150 Hz TENS increased tail-flick latencies by 35 min post-treatment, which was partially inhibited by naloxone pre-treatment and totally inhibited by cannabidiol (1.5mg/kg). These data suggest the involvement of the endogenous opioid system and the cannabinoid-mediated neuromodulation of the antinociception induced by transcutaneous electrostimulation at 10 Hz and 150 Hz TENS.
Assuntos
Canabidiol/metabolismo , Dor Nociceptiva/metabolismo , Dor Nociceptiva/terapia , Peptídeos Opioides/metabolismo , Sistema Nervoso Periférico/fisiologia , Estimulação Elétrica Nervosa Transcutânea , Animais , Canabidiol/farmacologia , Diazepam/farmacologia , Hipnóticos e Sedativos/farmacologia , Masculino , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Peptídeos Opioides/efeitos dos fármacos , Medição da Dor , Sistema Nervoso Periférico/efeitos dos fármacos , Ratos , Ratos Wistar , Estimulação Elétrica Nervosa Transcutânea/métodosRESUMO
Objetivo: Determinar el efecto y actividad antinociceptiva de las hojas de Maytenus macrocarpa (Ruiz & Pav) Briq. ôchuchuhuasiõ mediante la prueba de contorsiones abdominales en roedor. Material y Métodos: Se utilizaron 40 ratones albinos machos, con pesos medios de 25g, se empleó la prueba de contorsiones abdominales para determinar la actividad antinociceptiva. El grupo Control, no recibió ninguna sustancia. Se administró extracto etanólico de las hojas de M. macrocarpa (Ruiz & Pav.) Briq. 2000 mg/kg, Tramadol 10 mg/kg y Diclofenaco sódico 10 mg/kg. Las sustancias fueron administradas por la vía oral una hora antes de la inducción de dolor. Para la validación estadística se usó la prueba de Shapiro-Wilk, ANOVA de una cola, Tukey, y Newman-Keuls. Resultados: El número de contorsiones abdominales fue 41+/- 3.04, 27+/- 3.55, 9 +/- 4.14, y 18 +/- 2.65 respectivamente. El porcentaje de inhibición de la conducta nociceptiva fue: 0%, 34%, 77%, y 55%. La prueba de ANOVA de una vía, demostró diferencias estadísticas (p<0.05, IC 95%), y la prueba de Tukey y Newman-Keuls, demostraron diferencias significativas entre los grupos, frente al control. Conclusiones: Se comprobó el efecto antinociceptivo de las hojas de Maytenus macrocarpa (Ruiz & Pav.) Briq. ôchuchuhuasiõ, en dosis de 2000 mg/kg.
Objetives: To determine the effect and antinociceptive activity of the leaves of Maytenus macrocarpa (Ruiz & Pav ) Briq . ôChuchuhuasi ô by the writhing test in rodents. Material and Methods: 40 male albino mice were used, with average weights of 25g, the writhing test was used to determine the antinociceptive activity. The experimental groups were: Control; received no substance, ethanol extract of the leaves of M. macrocarpa Briq (Ruiz & Pav.) 2000 mg/kg, Tramadol 10 mg/kg and 10mg Sodium Diclofenac /kg. The substances were administered orally one hour before the induction of pain. For statistical validation the Shapiro -Wilk test, one-tailed ANOVA, Tukey, and Newman -Keuls was used. Results: Writhing number was 41 +/- 3.04, 27 +/- 3.55, 9 +/- 4.14, and 18 +/- 2.65 respectively. The inhibition percentage of the nociceptive behavior was: 0%, 34%, 77% and 55%. The test of one-way ANOVA showed statistical differences (p < 0.05, 95% CI), and the Tukey and Newman-Keuls test showed significant differences between groups versus control. Conclusions: Antinociceptive effect of the leaves of Maytenus macrocarpa (Ruiz & Pav.) Briq ôChuchuhuasiô was found at doses of 2000 mg/kg.
Assuntos
Dor Nociceptiva/terapia , Extratos Vegetais/uso terapêutico , Maytenus , Plantas Medicinais , Camundongos , Grupos ControleRESUMO
UNLABELLED: Acupuncture-induced analgesia depends on the activation of endogenous pain modulation pathways. In this study, we asked whether ascending nociceptive control (ANC), a form of pain-induced analgesia, contributes to the antinociceptive effect of acupuncture. To answer this question, we tested the ability of procedures that block ANC-induced analgesia, at peripheral, spinal, nucleus accumbens and rostral ventral medulla levels, to block acupuncture-induced analgesia. Acupuncture at ST36 (Zusanli), a widely used acupoint located in the hind limb, induced potent heterosegmental antinociception in the orofacial formalin test. The magnitude of this antinociceptive effect was similar to that induced by an intraplantar injection of capsaicin, a procedure classically used to activate ANC. The antinociceptive effect of acupuncture was blocked by sciatic C-fibers depletion (1% perineural capsaicin), spinal administration of a µ-opioid (Cys2,Tyr3,Orn5,Pen7amide, .2 µg) or of a GABAA (bicuculline, .3 µg) receptor antagonist, intra-nucleus accumbens administration of a µ-opioid receptor antagonist (Cys2,Tyr3,Orn5,Pen7amide, 1 µg), or intrarostral ventral medulla administration of a nicotinic acetylcholine receptor antagonist (mecamylamine, .6 µg). In addition, acupuncture at ST36 and/or upper lip formalin induced c-Fos expression in the nucleus accumbens and in rostral ventral medulla. On the basis of these results, we propose that ANC contributes to the antinociceptive effect of acupuncture. PERSPECTIVE: This article presents a novel mechanism of acupuncture analgesia, contributing to the understanding of its scientific basis. Because ANC is a pain modulation pathway activated by peripheral noxious stimulation that ascends to supraspinal regions, it could be the link between acupoint stimulation and the central mechanisms underlying acupuncture analgesia.
Assuntos
Analgesia por Acupuntura , Dor Aguda/fisiopatologia , Vias Aferentes/fisiologia , Nociceptividade/fisiologia , Dor Nociceptiva/fisiopatologia , Dor Aguda/terapia , Animais , Modelos Animais de Doenças , Masculino , Dor Nociceptiva/terapia , Medição da Dor , Ratos , Ratos WistarRESUMO
OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/biossíntese , Diabetes Mellitus Experimental/metabolismo , Dor Nociceptiva/terapia , Condicionamento Físico Animal/fisiologia , Medula Espinal/metabolismo , Animais , Glicemia/análise , Peso Corporal , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Modelos Animais de Doenças , Teste de Esforço , Imuno-Histoquímica , Masculino , Dor Nociceptiva/fisiopatologia , Ratos , Ratos Wistar , Estreptozocina , Fatores de TempoRESUMO
OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.
Assuntos
Animais , Masculino , Ratos , Peptídeo Relacionado com Gene de Calcitonina/biossíntese , Diabetes Mellitus Experimental/metabolismo , Dor Nociceptiva/terapia , Condicionamento Físico Animal/fisiologia , Medula Espinal/metabolismo , Peso Corporal , Glicemia/análise , Modelos Animais de Doenças , Complicações do Diabetes/metabolismo , Complicações do Diabetes/fisiopatologia , Diabetes Mellitus Experimental/fisiopatologia , Teste de Esforço , Imuno-Histoquímica , Dor Nociceptiva/fisiopatologia , Ratos Wistar , Estreptozocina , Fatores de TempoRESUMO
AIMS: The purpose of this study was to examine whether the use of intraperitoneal or intrathecal amitriptyline combined with electroacupuncture modifies the tail-flick reflex and incision pain in rats that normally do not have analgesia to electroacupuncture in the tail-flick test (non-responder rats). MAIN METHODS: Changes in the nociceptive threshold of intraperitoneal or intrathecal saline- or amitriptyline-treated non-responder rats were evaluated using the tail-flick or incision pain tests before, during and after a 20-min period of electroacupuncture, applied at 2 Hz to the Zusanli and Sanynjiao acupoints. Amitriptyline was used at doses of 0.8 mg/kg or 30 µg/kg by intraperitoneal or intrathecal route, respectively. At these doses, amitriptyline has no effect against thermal or incision pain in rats. KEY FINDINGS: Rats selected as non-responders to the analgesic effect of electroacupuncture 2 Hz in tail-flick and incision pain tests become responders after an intraperitoneal or intrathecal injection of amitriptyline. SIGNIFICANCE: Amitriptyline converts non-responder rats to rats that respond to electroacupuncture with analgesia in a model of thermal phasic pain and anti-hyperalgesia in a model of incision pain.
Assuntos
Amitriptilina/uso terapêutico , Eletroacupuntura , Dor Nociceptiva/terapia , Limiar da Dor/efeitos dos fármacos , Analgésicos não Narcóticos/uso terapêutico , Animais , Terapia Combinada , Infusões Parenterais , Injeções Espinhais , Masculino , Ratos , Ratos WistarRESUMO
This study investigated the antinociceptive and anti-inflammatory effects of electroacupuncture (EA) on zymosan-induced acute arthritis of the rat temporomandibular joint (TMJ). Male Wistar rats were injected with saline or zymosan (control group; 2 mg) into the left TMJ. Low frequency EA (10 Hz, 30 min) was performed at acupoints (LI4, LI11, ST36, ST44) or sham points 2 h after or 1 h before zymosan administration. Mechanical hypernociception was accessed by the electronic Von Frey method after zymosan administration. Rats were sacrificed 6 h after zymosan administration and the joint was removed for histopathological analysis, myeloperoxidase activity assessment, vascular permeability observations, and immunohistochemical verification of inflammatory mediators. The results showed that EA inhibited zymosan-induced hypernociception, compared with the control group and with the sham group (p < 0.05). The results showed that EA inhibited inflammatory parameters such as neutrophil migration, vascular permeability, and tumour necrosis factor α (TNF-α), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expression in the TMJ compared with the sham group (p < 0.05). Histopathological analysis showed that EA significantly inhibited edema and periarticular infiltration (p < 0.05) compared with the control and sham groups. EA at acupoints produced antinociceptive and anti-inflammatory effects on zymosan-induced arthritis in the rat TMJ.