RESUMO
The intracranial compliance in type 2 diabetes mellitus (T2DM) patients and the association with cardiovascular autonomic control have not been fully elucidated. The aim of this study was to assess intracranial compliance using the noninvasive intracranial pressure (niICP) and the monitoring of waveform peaks (P1, P2, and P3) and the relationship with cardiovascular autonomic control in T2DM patients. Thirty-two men aged 40-60 years without cardiovascular autonomic neuropathy (CAN) were studied: T2DMG (n=16) and control group CG (n=16). The niICP was evaluated by a noninvasive extracranial sensor placed on the scalp. Cardiovascular autonomic control was evaluated by indices of the baroreflex sensitivity (BRS), from temporal series of R-R intervals of electrocardiogram and systolic arterial pressure, during supine and orthostatic positions. The participants remained in the supine position for 15 min and then 15 min more in orthostatism. T2DMG presented a decrease of the P2/P1 ratio during the orthostatic position (P<0.001). There was a negative moderate correlation between the P2 peak with cardiovascular coupling (K2HP-SAPLF) in supine (r=-0.612, P=0.011) and orthostatic (r=-0.568, P=0.020) positions in T2DMG. We concluded that T2DM patients without CAN and cardiovascular complications presented intracranial compliance similar to healthy subjects. Despite preserved intracranial adjustments, T2DM patients had a response of greater magnitude in orthostatism. In addition, the decoupling between the heart period and blood pressure signal oscillations in low frequency appeared to be related to the worsening of intracranial compliance due to the increased P2 peak.
Assuntos
Diabetes Mellitus Tipo 2 , Sistema Nervoso Autônomo/fisiologia , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Diabetes Mellitus Tipo 2/complicações , Coração , Humanos , MasculinoRESUMO
The intracranial compliance in type 2 diabetes mellitus (T2DM) patients and the association with cardiovascular autonomic control have not been fully elucidated. The aim of this study was to assess intracranial compliance using the noninvasive intracranial pressure (niICP) and the monitoring of waveform peaks (P1, P2, and P3) and the relationship with cardiovascular autonomic control in T2DM patients. Thirty-two men aged 40-60 years without cardiovascular autonomic neuropathy (CAN) were studied: T2DMG (n=16) and control group CG (n=16). The niICP was evaluated by a noninvasive extracranial sensor placed on the scalp. Cardiovascular autonomic control was evaluated by indices of the baroreflex sensitivity (BRS), from temporal series of R-R intervals of electrocardiogram and systolic arterial pressure, during supine and orthostatic positions. The participants remained in the supine position for 15 min and then 15 min more in orthostatism. T2DMG presented a decrease of the P2/P1 ratio during the orthostatic position (P<0.001). There was a negative moderate correlation between the P2 peak with cardiovascular coupling (K2HP-SAPLF) in supine (r=-0.612, P=0.011) and orthostatic (r=-0.568, P=0.020) positions in T2DMG. We concluded that T2DM patients without CAN and cardiovascular complications presented intracranial compliance similar to healthy subjects. Despite preserved intracranial adjustments, T2DM patients had a response of greater magnitude in orthostatism. In addition, the decoupling between the heart period and blood pressure signal oscillations in low frequency appeared to be related to the worsening of intracranial compliance due to the increased P2 peak.
RESUMO
Artemisinin (ART) was initially described for the control of inflammation and pain. However, the mechanisms involved with its antinociceptive effect are still poorly understood. Thus, this present study aimed to investigate the effect of ART in both free and nanocapsulated form on postoperative pain, as well as the participation of the spinal Toll-like receptor 4 (TLR4) in this process. Postoperative pain was induced using the skin/muscle incision retraction (SMIR) model in male Swiss mice. After 3 and 28 days of SMIR, the animals received an intrathecal injection of free or nanocapsulated ART, and the nociceptive threshold was evaluated by von Frey filament test. To evaluate the involvement of the microglia, astrocytes, and TLR4, minocycline (a microglia inhibitor), fluorocitrate (an astrocyte inhibitor), and Lipopolysaccharide Rhodobacter sphaeroides (LPS-RS), a TLR4 antagonist, were intrathecally injected on the third day of SMIR. The levels of spinal TLR4 protein and proinflammatory cytokines tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1ß) were quantified by western blot and enzyme-linked immunosorbent assay, respectively. The results showed that free ART reduced postoperative pain (P < 0.001, F5,30 = 7.49, 16.66% for 1000 ng dose; and P < 0.01, F5,30 = 7.49, 14.58% for 500 ng dose) on the 3rd day of SMIR; while the ART nanocapsule had this effect on both the third (P < 0.001; F5,30 = 4.94; 43.75, 39.58 and 72.91% for the 250, 500 and 1000 ng doses, respectively) and 28th (P < 0.05; F5,30 = 7.71; 29.16 and 33.33% for the 500 and 1000 ng doses, respectively) day. The ART nanocapsule had a more potent and longer antinociceptive effect than free ART or morphine. Postoperative pain was also reduced by minocycline and LPS-RS. The ART nanocapsule also reduced the increased levels of TLR4, TNF-α, and IL-1ß induced by SMIR. These data suggest that the ART nanocapsule has a potent analgesic effect on postoperative pain at the spinal level, and this response involves the inhibition of TLR4 and the proinflammatory cytokines TNF-α and IL-1ß.
Assuntos
Analgésicos/farmacologia , Artemisininas/farmacologia , Nanocápsulas/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Receptor 4 Toll-Like/antagonistas & inibidores , Animais , Citocinas/metabolismo , Hiperalgesia/tratamento farmacológico , Hiperalgesia/metabolismo , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Dor Pós-Operatória/metabolismo , Medula Espinal/metabolismo , Regulação para Cima/efeitos dos fármacosRESUMO
Oligodendrocytes are glial cells responsible for the myelination of axons within the central nervous system. Many studies have demonstrated that glial cells, mainly microglia and astrocytes, are actively involved in many pathological pain states. Although oligodendrocytes have been widely studied in relation to neurodegenerative diseases, their role in pain genesis in the spinal cord is minimally described and not well understood. Few studies have proposed novel molecules or mechanisms of interaction with consistent evidence of oligodendrocyte participation in the central pain process; however, recent findings support a potential role of oligodendrocytes in chronic pain. Therefore, this review aimed to gather and analyze scientific findings related to the contribution of oligodendrocytes to this symptom. Based on these previous studies, we focused on describing the specific mechanisms involved in the participation of oligodendrocytes in pain genesis.
Assuntos
Dor Crônica/patologia , Oligodendroglia/patologia , Animais , Sistema Nervoso Central/patologia , Humanos , Neuroglia/patologiaRESUMO
Exercise-induced analgesia is a phenomenon discussed worldwide. This effect began to be investigated in the early 1970s in healthy individuals and rodents during and after an acute or chronic session of running or swimming. Thereafter, studies found this effect was also induced by resistance exercises. Over the years, many studies have demonstrated the importance of exercise-induced analgesia in relieving pain caused by different conditions, such as fibromyalgia, low back pain, neuropathy, and osteoarthritis. This review aims to provide the reader with an in-depth description of the main endogenous systems, substances, neurotransmitters, receptors and enzymes that are thought to be involved in the analgesic effect induced by exercise. Many hypotheses have been proposed to elucidate the mechanisms responsible for exercise-induced analgesia. One of the most accepted hypotheses has been the activation of several endogenous systems described as analgesics. Studies have demonstrated that during and after exercise different endogenous systems are activated, which release substances or neurotransmitters, such as opioids, nitric oxide, serotonin, catecholamines and endocannabinoids, that may modulate the pain perception.
Assuntos
Analgesia , Exercício Físico , Analgésicos Opioides/metabolismo , Animais , Catecolaminas/metabolismo , Citocinas/metabolismo , Endocanabinoides/metabolismo , Humanos , Óxido Nítrico/metabolismo , Serotonina/metabolismoRESUMO
Orofacial pain is pain perceived in the face and/or oral cavity, generally caused by diseases or disorders of regional structures, by dysfunction of the nervous system, or through referral from distant sources. Treatment of orofacial pain is mainly pharmacological, but it has increased the number of reports demonstrating great clinical results with the use of non-pharmacological therapies, among them electroacupuncture. However, the mechanisms involved in the electroacupuncture are not well elucidated. Thus, the present study investigate the involvement of the nitric oxide synthase (NOS) and ATP sensitive K+ channels (KATP) in the antinociception induced by electroacupuncture (EA) at acupoint St36. Thermal nociception was applied in the vibrissae region of rats, and latency time for face withdrawal was measured. Electrical stimulation of acupoint St36 for 20 minutes reversed the thermal withdrawal latency and this effect was maintained for 150 min. Intraperitoneal administration of specific inhibitors of neuronal nitric oxide synthase (nNOS), inducible nitric oxide synthase (iNOS) and a KATP channels blocker reversed the antinociception induced by EA. Furthermore, nitrite concentration in cerebrospinal fluid (CSF) and plasma, increased 4 and 3-fold higher, respectively, after EA. This study suggests that NO participates of antinociception induced by EA by nNOS, iNOS and ATP-sensitive K+ channels activation.
Assuntos
Pontos de Acupuntura , Eletroacupuntura , Dor Facial/terapia , Manejo da Dor , Animais , Dor Facial/fisiopatologia , Temperatura Alta/efeitos adversos , Canais KATP/antagonistas & inibidores , Canais KATP/fisiologia , Masculino , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Óxido Nítrico Sintase Tipo I/fisiologia , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/fisiologia , Nitritos/sangue , Nitritos/líquido cefalorraquidiano , Ratos WistarRESUMO
Nitric oxide (NO) is a soluble gas that participates in important functions of the central nervous system, such as cognitive function, maintenance of synaptic plasticity for the control of sleep, appetite, body temperature, neurosecretion, and antinociception. Furthermore, during exercise large amounts of NO are released that contribute to maintaining body homeostasis. Besides NO production, physical exercise has been shown to induce antinociception. Thus, the present study aimed to investigate the central involvement of NO in exercise-induced antinociception. In both mechanical and thermal nociceptive tests, central [intrathecal (it) and intracerebroventricular (icv)] pretreatment with inhibitors of the NO/cGMP/KATP pathway (L-NOArg, ODQ, and glybenclamide) prevented the antinociceptive effect induced by aerobic exercise (AE). Furthermore, pretreatment (it, icv) with specific NO synthase inhibitors (L-NIO, aminoguanidine, and L-NPA) also prevented this effect. Supporting the hypothesis of the central involvement of NO in exercise-induced antinociception, nitrite levels in the cerebrospinal fluid increased immediately after AE. Therefore, the present study suggests that, during exercise, the NO released centrally induced antinociception.
Assuntos
Inibidores Enzimáticos/farmacologia , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/metabolismo , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Condicionamento Físico Animal/fisiologia , Animais , Masculino , Óxido Nítrico/líquido cefalorraquidiano , Medição da Dor , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacosRESUMO
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.
Assuntos
Animais , Feminino , Ratos , Analgesia , Condicionamento Físico Animal , Limiar da Dor/efeitos dos fármacos , Treinamento Resistido , Receptores Opioides/fisiologia , Medição da Dor , Limiar da Dor/fisiologia , Ratos WistarRESUMO
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%, P < 0.05) in the nociceptive threshold was produced immediately after exercise, decreasing to 15% 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.
Assuntos
Analgesia , Limiar da Dor/efeitos dos fármacos , Condicionamento Físico Animal , Receptores Opioides/fisiologia , Treinamento Resistido , Animais , Feminino , Medição da Dor , Limiar da Dor/fisiologia , Ratos , Ratos WistarRESUMO
Davilla elliptica St Hill (Dilleniaceae) is widely used for multiple purposes in Brazil. The aim of this study was to verify the pharmacological support of this folk use and evaluate its use as antinociceptive. The hydroalcoholic extract of the stems (100-1000 mg/kg, p.o.) induced reduction of response in the formalin test inflammatory phase in mice. This antinociceptive effect does not involve the opioidergic pathway since it was not reverted by pre-treatment with naloxone nor due to myorelaxant activity since it did not affect rota-rod and tail-flick performance. Our results indicate a participation of the nitrergic pathway and may be of particular potential importance in clinical medicine, in view of the current interest in the assessment of new medicines originated from plants.