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Neuroscience Bulletin ; (6): 1493-1509, 2021.
Article in English | WPRIM | ID: wpr-922651


The periaqueductal gray (PAG) is a complex mesencephalic structure involved in the integration and execution of active and passive self-protective behaviors against imminent threats, such as immobility or flight from a predator. PAG activity is also associated with the integration of responses against physical discomfort (e.g., anxiety, fear, pain, and disgust) which occurs prior an imminent attack, but also during withdrawal from drugs such as morphine and cocaine. The PAG sends and receives projections to and from other well-documented nuclei linked to the phenomenon of drug addiction including: (i) the ventral tegmental area; (ii) extended amygdala; (iii) medial prefrontal cortex; (iv) pontine nucleus; (v) bed nucleus of the stria terminalis; and (vi) hypothalamus. Preclinical models have suggested that the PAG contributes to the modulation of anxiety, fear, and nociception (all of which may produce physical discomfort) linked with chronic exposure to drugs of abuse. Withdrawal produced by the major pharmacological classes of drugs of abuse is mediated through actions that include participation of the PAG. In support of this, there is evidence of functional, pharmacological, molecular. And/or genetic alterations in the PAG during the impulsive/compulsive intake or withdrawal from a drug. Due to its small size, it is difficult to assess the anatomical participation of the PAG when using classical neuroimaging techniques, so its physiopathology in drug addiction has been underestimated and poorly documented. In this theoretical review, we discuss the involvement of the PAG in drug addiction mainly via its role as an integrator of responses to the physical discomfort associated with drug withdrawal.

Amygdala , Humans , Morphine , Nociception , Periaqueductal Gray , Substance-Related Disorders
Acta sci. vet. (Impr.) ; 49: Pub 1822, 2021. tab
Article in English | LILACS, VETINDEX | ID: biblio-1363835


Many variations of ovariohysterectomy techniques have been described, including the traditional one and minimally invasive procedures. Non-laparoscopic Snook hook technique is an alternative for performing minimally invasive ovariohysterectomy. Few studies have been carried out in order to assess pain in animals submitted to minimally invasive surgeries, especially involving one of the most performed surgical procedures in veterinary practice. The aim of this study was to evaluate surgical duration, intraoperative nociception and acute postoperative pain after traditional ovariohysterectomy or minimally invasive non-laparoscopic technique in dogs using Snook hook. The hypothesis is that non-laparoscopic minimally invasive ovariohysterectomy would be faster and less painful than the conventional technique. Thirty dogs were divided into Traditional Group (TG = 15) and Minimally Invasive Group (MIG = 15). Heart rate, respiratory rate, systolic blood pressure, body temperature, oxyhemoglobin saturation, end-tidal carbon dioxide concentration (ETCO2) and end-tidal isoflurane concentration were evaluated before the surgery begins (M0), during incision (M1), clamping of the first ovarian pedicle (M2), second ovarian pedicle (M3), uterine cervix (M4), abdominal suture (M5) and at the end of surgery (M6). The modified Glasgow Pain Scale was used for acute postoperative pain assessment and Visual Analogue Scale (VAS) was used to assess the sensitivity of surgical wound. The level of significance established for all statistical analysis was 5%. Statistical differences were not observed between groups considering total surgical time and postoperative acute pain intensity (P > 0.05), in spite of MIG having shorter duration of surgery. There was no statistical difference between groups considering all intraoperative parameters except respiratory rate (TG < MIG; P < 0.05) and ETCO2 (MIG < TG; P < 0.05) at the moment of traction of the first ovarian pedicle (M2). Pain assessment by VAS showed statistical difference 24h after the end of surgery (TG < MIG) (P < 0.05). Both procedures were similar regarding intraoperative nociception and acute postoperative pain. It is possible that the sensation of pain in both procedures was blocked by the effectiveness of analgesics, once they might cause an inhibition of painful behaviors limiting a possible difference in pain identification. Higher respiratory stress observed in MIG at M2 and higher pain score by VAS noted in MIG 24 h after the end of surgery can be justified by greater traction of ovarian pedicle, due to limited surgical access of minimally invasive technique. Minimally invasive ovariohysterectomy non-laparoscopic seems to be potentially faster, probably due to the smaller size of the abdominal incision, which takes less time to be closed. In the present study, both techniques were performed by an experienced surgeon, providing safe procedures, nevertheless it is important to emphasize that iatrogenic injury can be caused by surgeons non-proficient in the Snook hook technique, considering the limited visualization of anatomical abdominal structures. Data obtained indicate that traditional ovariohysterectomy and non-laparoscopic Snook hook technique promote similar intraoperative nociception and acute postoperative pain, however minimally invasive procedure is potentially faster with less surgical trauma.(AU)

Animals , Female , Dogs , Pain, Postoperative/veterinary , Ovariectomy/veterinary , Dog Diseases/surgery , Nociception , Hysterectomy/veterinary , Dogs
Braz. j. med. biol. res ; 54(10): e11207, 2021. tab, graf
Article in English | LILACS | ID: biblio-1285643


Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.

Animals , Rats , Neuralgia/drug therapy , Antioxidants , Sciatic Nerve , Spinal Cord , Vitamin D , Vitamins , Reactive Oxygen Species , Rats, Wistar , Nociception , Hydrogen Peroxide , Hyperalgesia/drug therapy
Rev. Ciênc. Méd. Biol. (Impr.) ; 19(3): 507-513, dez 5, 2020. fig
Article in Portuguese | LILACS | ID: biblio-1358030


A dor miofascial orofacial vem sendo tratada com analgésicos, anti-inflamatórios, relaxantes musculares, fisioterapia, laserterapia e placas oclusais. Contudo, muitas vezes, tais condutas falham em amenizar o quadro doloroso, havendo a necessidade de testar outras estratégias de tratamento. Metodologia: Uma opção para avaliação experimental dessas terapias seria o teste de dor induzido pela carragenina, associado ao teste de avaliação do limiar nociceptivo, originalmente desenvolvido para avaliar a ação de drogas nas patas de roedores. Sendo assim, o presente estudo analisou a nocicepção causada pela carragenina em masseteres de ratos, através do teste de Von Frey, correlacionando-a com alterações teciduais produzidas por esta droga. A carragenina foi injetada no músculo masseter de ratos, enquanto o grupo controle recebeu soro fisiológico. O limiar nociceptivo foi mensurado com um analgesímetro digital antes da administração da carragenina e 5 horas, 1, 3 e 7 dias após o seu uso. Decorridos 8 dias da intervenção, os animais foram eutanasiados, sendo seus masseteres encaminhados para processamento histológico e coloração H&E. Resultados: Observou-se uma diminuição do limiar da resposta nociceptiva em todos os períodos no grupo com carragenina, quando comparado com o grupo controle, havendo diferença estatisticamente significante nas 5 horas. A análise histológica do grupo experimental mostrou a presença de espaços perimisial e endomisial alargados e preenchidos por uma matriz com alguns linfócitos, muitos macrófagos e raros mastócitos. Conclusão: Os resultados indicaram que a associação de uma droga inflamatória com o método Von Frey pode ser uma opção para o estudo do efeito de terapias de dor miofascial.

Myofascial orofacial pain has been treated with analgesics, anti-inflammatories, muscle relaxants, physiotherapy, laser therapy and occlusal plaques. However, many times, such behaviors fail to alleviate the painful condition, with the need to test other treatment strategies. Methodology: An option for experimental evaluation of these therapies would be the pain test induced by carrageenan associated with the nociceptive threshold assessment test, originally developed to assess the action of drugs on the rodents' feet. Thus, the present study analyzed the nociception caused by carrageenan in rat masseter using the Von Frey test, correlating it with tissue changes produced by this drug. Carrageenan was injected into the masseter muscle of rats, while the control group received saline. The nociceptive threshold was measured with a digital analgesometer before administration of carrageenan and 5 hours, 1, 3 and 7 days after its use. After 8 days of the intervention, the animals were euthanized, and their masseters were sent for histological processing and H&E staining. Results: There was a decrease in the nociceptive response threshold in all periods in the group treated with carrageenan when compared to the control group, with a statistically significant difference at 5 hours. Histological analysis of the experimental group showed the presence of enlarged perimisial and endomisial spaces, filled by a matrix with some lymphocytes, many macrophages and rare mast cells. Conclusion: Results indicated that the association of an inflammatory drug with the Von Frey method may be an option for studying the effect of therapies on myofascial pain.

Animals , Male , Rats , Rats, Inbred Strains , Carrageenan , Nociception , Myofascial Pain Syndromes , Physical Therapy Modalities , Occlusal Splints , Analgesics , Anti-Inflammatory Agents , Muscle Relaxants, Central
Rev. bras. anestesiol ; 70(6): 678-681, Nov.-Dec. 2020. tab
Article in English, Portuguese | LILACS | ID: biblio-1155781


Abstract Background: Opioid-free anesthesia decreases the incidence of opioid adverse events, but its optimal antinociceptive depth has not been clearly defined. Personalizing intraoperative opioid-free infusions with a nociception monitor may be the solution. Case report: We describe the feasibility and potential limitations of titrating opioid-free antinociception during major abdominal surgery using the Analgesia Nociception Index (Mdoloris, Lille, France) in an obese patient. After stabilizing the patient's nociception-antinociception balance intraoperatively we quickly reversed anesthesia and the patient did not require postoperative opioids. Conclusion: Personalizing opioid-free antinociception with a nociception monitor is feasible. It may optimize intraoperative antinociception and improve postoperative comfort.

Resumo Introdução A anestesia sem opioides diminui a incidência de eventos adversos associados aos opioides, mas a profundidade antinociceptiva ideal dessa abordagem não está claramente definida. Personalizar a infusão intraoperatória sem opioides com o uso de monitor de nocicepção pode ser a solução. Relato de caso Descrevemos a viabilidade e as eventuais limitações da titulação da antinocicepção sem opioides por meio do uso do Índice de Analgesia/Nocicepção (Mdoloris, Lille, França) durante cirurgia abdominal de grande porte em paciente com obesidade. Depois de estabilizar o equilíbrio nocicepção-antinocicepção da paciente no intraoperatório, revertemos rapidamente a anestesia e a paciente não precisou de opioides no pós-operatório. Conclusão A personalização da antinocicepção sem opioides por meio do emprego de monitor de nocicepção é factível. A abordagem pode otimizar a antinocicepção intraoperatória e melhorar o conforto pós-operatório.

Humans , Female , Urinary Incontinence/surgery , Vesicovaginal Fistula/surgery , Precision Medicine/methods , Nociception , Anesthesia, Inhalation , Anesthesia, Intravenous , Urinary Incontinence/etiology , Obesity, Morbid/complications , Vesicovaginal Fistula/complications , Electroencephalography , Analgesia/instrumentation , Analgesia/methods , Analgesics, Opioid/adverse effects , Middle Aged
Rev. bras. anestesiol ; 69(4): 396-402, July-Aug. 2019. tab, graf
Article in English | LILACS | ID: biblio-1041998


Abstract Background and objectives Patient self-rating based scales such as Numerical Rating Scale, Visual Analog Scale that is used for postoperative pain assessment may be problematic in geriatric or critically ill patients with communication problems. A method capable of the assessment of pain in objective manner has been searched for years. Analgesia nociception index, which is based on electrocardiographic data reflecting parasympathetic activity, has been proposed for this. In this study we aimed to investigate the effectiveness of analgesia nociception index as a tool for acute postoperative pain assessment. Our hypothesis was that analgesia nociception index may have good correlation with Numerical Rating Scale values. Methods A total of 120 patients of American Society of Anesthesiologists (ASA) physical status I and II undergoing any surgical procedure under halogenated-based anesthesia with fentanyl or remifentanil were enrolled for the study. At the 15th minute of arrival to the Postoperative Care Unit the patients' pain was rated on a 0-10 point Numerical Rating Scale. The patients' heart rate, blood pressure, and analgesia nociception index scores were simultaneously measured at that time. The correlation between analgesia nociception index, heart rate, blood pressure and Numerical Rating Scale was examined. Results The study was completed with 107 patients, of which 46 were males (43%). Mean (SD) analgesia nociception index values were significantly higher in patients with initial Numerical Rating Scale ≤3, compared with Numerical Rating Scale >3 (69.1 [13.4] vs. 58.1 [12.9] respectively, p < 0.001). A significant negative linear relationship (r 2 = -0.312, p = 0.001) was observed between analgesia nociception index and Numerical Rating Scale. Conclusion Analgesia nociception index measurements at postoperative period after volatile agent and opioid-based anesthesia correlate well with subjective Numerical Rating Scale scores.

Resumo Justificativa e objetivo As escalas baseadas na autoavaliação de pacientes, como a Escala Visual Numérica e a Escala Visual Analógica, que são usadas para avaliar a dor pós-operatória podem ser problemáticas em pacientes geriátricos ou em estado crítico com problemas de comunicação. Portanto, um método capaz de avaliar a dor de maneira objetiva vem sendo pesquisado há anos. O índice de analgesia/nocicepção, baseado em dados eletrocardiográficos que refletem a atividade parassimpática, tem sido proposto para tal avaliação. Neste estudo, objetivamos investigar a eficácia do índice de analgesia/nocicepção como uma ferramenta para a avaliação da dor pós-operatória aguda. Nossa hipótese foi que o índice de analgesia/nocicepção pode ter boa correlação com os valores da Escala de Classificação Numérica. Métodos Um total de 120 pacientes com estado físico ASA I e II, submetidos a qualquer procedimento cirúrgico com o uso de anestésicos halogenados associados a fentanil ou remifentanil, foi incluído no estudo. No 15º minuto após a chegada à sala de recuperação pós-anestesia, a dor dos pacientes foi avaliada em uma escala numérica de 0-10 pontos. Os escores de frequência cardíaca, pressão arterial e o índice de analgesia/nocicepção dos pacientes foram medidos simultaneamente naquele momento. A correlação entre o índice de analgesia/nocicepção, frequência cardíaca, pressão arterial e a Escala Visual Numérica foi avaliada. Resultados O estudo foi concluído com 107 pacientes, dos quais 46 eram do sexo masculino (43%). Os valores da média (DP) do índice de analgesia/nocicepção foram significativamente maiores nos pacientes com valor inicial na Escala Visual Numérica ≤ 3, em comparação com valor na mesma escala > 3 (69,1 [13,4] vs. 58,1 [12,9], respectivamente, p < 0,001). Uma relação linear negativa significativa (r2 = -0,312, p = 0,001) foi observada entre o índice de analgesia/nocicepção e a Escala Visual Numérica. Conclusão As mensurações do índice de analgesia/nocicepção no pós-operatório após anestesia com agentes halogenados e opioides mostraram boa correlação com os escores subjetivos da Escala Visual Numérica.

Humans , Male , Female , Adult , Young Adult , Pain Measurement/methods , Acute Pain/diagnosis , Nociception/drug effects , Analgesia/methods , Pain, Postoperative/diagnosis , Pain, Postoperative/prevention & control , Fentanyl/administration & dosage , Prospective Studies , Acute Pain/prevention & control , Remifentanil/administration & dosage , Analgesics, Opioid/administration & dosage , Middle Aged
S. Afr. fam. pract. (2004, Online) ; 61(1): 6-12, 2019. ilus
Article in English | AIM, AIM | ID: biblio-1270074


Pain is a complex and unique experience. It encompasses several pathways, involving nociceptive signal generation (transduction) and propagation (transmission), as well as perception and modulation of the nociceptive stimuli. Nonsteroidal anti-inflammatory drugs (NSAIDs) primarily exert their analgesic effects through inhibition of cyclooxygenase (COX) enzymes, thereby attenuating prostaglandin synthesis. The COX-2 selective NSAIDs (coxibs) and aspirin have also been shown to reduce colorectal cancers,presumably by prostaglandin-inhibition mechanisms. Paracetamol appears to have both peripheral and central effects. The postulated mechanism for its peripheral effects is indirect COX inhibition, while the central effects are thought to be mediated by modulation of descending pain inhibition pathways. Topical analgesics are available in various formulations. The topical NSAIDs have the same mechanism of action as the systemic formulations, but with less systemic absorption and effects. The local anaesthetics provide a dense sensory block via inhibition of nerve impulse transmission, and are available in percutaneous and transdermal preparations. Capsicum is effective forneuropathic pain, and acts by stimulating and then desensitising peripheral sensory nerves

Acetaminophen , Analgesia , Anti-Inflammatory Agents, Non-Steroidal , Bread , Nociception , South Africa
Article in English | WPRIM | ID: wpr-765949


BACKGROUND/AIMS: Abdominal pain can be evoked or exacerbated after gastrointestinal cold stimulation in some patients with diarrhea-predominant irritable bowel syndrome (IBS-D), indicating a low temperature-induced sensitization of visceral perception. We investigated the role of vagal transient receptor potential ankyrin 1 (TRPA1, a cold-sensing ion channel) in cold-aggravated visceral mechanonociception in a stress-induced IBS animal model. METHODS: TRPA1 expression was examined in antral biopsies of healthy controls and IBS-D patients. Abdominal symptoms were assessed before and after warm or cold water intake. The visceromotor response (VMR) to colorectal distention (CRD) following intra-antral infusion of cold saline was measured in animals undergoing sham or chronic water avoidance stress. TRPA1 expression, extracellular signal-regulated protein kinase 1/2 (ERK1/2) phosphorylation, and neuronal calcium influx in vagal afferents were assessed. RESULTS: Compared to healthy controls, IBS-D patients displayed elevated antral TRPA1 expression, which was associated with symptom scores after cold (4°C) water intake. Intra-antral infusion of cold saline increased VMR to CRD in naive rats, an effect dependent on vagal afferents. In stressed rats, this effect was greatly enhanced. Functional blockade and gene deletion of TRPA1 abolished the cold effect on visceral nociception. TRPA1 expression in vagal (but not spinal) afferents increased after stress. Moreover, the cold-induced, TRPA1-dependent ERK1/2 activation and calcium influx in nodose neurons were more robust in stressed rats. CONCLUSIONS: Stress-exaggerated visceral mechanonociception after antral cold exposure may involve up-regulation of TRPA1 expression and function on vagal afferents. Our findings reveal a novel mechanism for abnormal gastrointestinal cold sensing in IBS.

Abdominal Pain , Animals , Ankyrins , Biopsy , Calcium , Cold Temperature , Drinking , Gene Deletion , Humans , Irritable Bowel Syndrome , Models, Animal , Neurons , Nociception , Phosphorylation , Protein Kinases , Rats , Stress, Psychological , Up-Regulation , Vagus Nerve , Visceral Pain , Water
Article in English | WPRIM | ID: wpr-763039


The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.

Capsaicin , Ligands , Nociception
The Korean Journal of Pain ; : 168-177, 2019.
Article in English | WPRIM | ID: wpr-761701


BACKGROUND: Brennan’s rodent paw incision model has been extensively used for understanding mechanisms underlying postoperative pain in humans. However, alterations of physiological parameters like blood pressure and heart rate, or even feeding and drinking patterns after the incision have not been documented as yet. Moreover, though eicosanoids like prostaglandins and leukotrienes contribute to inflammation, tissue levels of these inflammatory mediators have never been studied. This work further investigates the antinociceptive effect of protein C after intra-wound administration. METHODS: Separate groups of Sprague–Dawley rats were used for quantitation of cyclooxygenase (COX) activity and leukotriene B4 level by enzyme-linked immunosorbent assay, as well as estimation of cardiovascular parameters and feeding and drinking behavior after paw incision. In the next part, rats were subjected to incision and 10 μg of protein C was locally administered by a micropipette. Both evoked and non-evoked pain parameters were then estimated. RESULTS: COX, particularly COX-2 activity and leukotriene B4 levels increased after incision. Hemodynamic parameters were normal. Feeding and drinking were affected on days 1 and 3, and on day 1, respectively. Protein C attenuated non-evoked pain behavior alone up to day 2. CONCLUSIONS: Based upon current observations, Brennan’s rodent paw incision model appears to exhibit a prolonged period of nociception similar to that after surgery, with minimal interference of physiological parameters. Protein C, which is likely converted to activated protein C in the wound, attenuated the guarding score, which probably represents pain at rest after surgery in humans.

Animals , Blood Pressure , Drinking , Drinking Behavior , Eicosanoids , Enzyme-Linked Immunosorbent Assay , Heart Rate , Hemodynamics , Humans , Inflammation , Leukotriene B4 , Leukotrienes , Nociception , Pain, Postoperative , Prostaglandin-Endoperoxide Synthases , Prostaglandins , Protein C , Rats , Rodentia , Wounds and Injuries
Article in English | WPRIM | ID: wpr-785372


Nociception monitoring devices using changes in autonomic nervous system activity have been developed in numerous ways. Although there have been few studies conducted on children, compared to the relatively higher number of studies on adults, most of the nociception monitors in children, as in adults, appear to be more useful than the standard clinical practice that uses hemodynamic parameters in the evaluation and treatment of intraoperative nociception (pain) during general anesthesia. Particularly, when monitoring the surgical pleth index (SPI) in anesthetized children, the application of a new target range of SPI values (≤ 40) to the SPI monitoring criteria seems to be necessary for providing a more proper intraoperative analgesia. The analgesia nociception index (ANI) shows promising results in anesthetized adults, and recently, positive results along with cardiorespiratory coherence have been reported in pediatric patients. Newborn infant parasympathetic evaluation (NIPE) could be useful for providing adequate analgesia in newborns, infants, and children under 2 years of age in anesthetized or awake states. In cases of skin conductance and pupillometry, further studies are needed. Understanding the pros, cons, and limitations of these nociception monitoring tools will provide more effective and safe intraoperative analgesia to pediatric patients undergoing general anesthesia, and it may also help to plan and conduct promising research on the use of perioperative nociception monitoring in pediatric patients in the future.

Adult , Analgesia , Anesthesia, General , Autonomic Nervous System , Child , Hemodynamics , Humans , Infant , Infant, Newborn , Monitoring, Intraoperative , Nociception , Pain Measurement , Skin
Article in English | WPRIM | ID: wpr-741642


The present study was conducted to investigate anti-nociceptive and anti-inflammatory effects of the leaves of Ilex latifolia Thunb (I. latifolia) in in vivo and in vitro. Writhing responses induced by acetic acid and formalin- and thermal stimuli (tail flick and hot plate tests)-induced pain responses for nociception were evaluated in mice. I. latifolia (50 – 200 mg/kg, p.o.) and ibuprofen (100 mg/kg, p.o.), a positive non-steroidal anti-inflammatory drug (NSAID), inhibited the acetic acid-induced writhing response and the second phase response (peripheral inflammatory response) in the formalin test, but did not protect against thermal nociception and the first phase response (central response) in the formalin test. These results show that I. latifolia has a significant anti-nociceptive effect that appears to be peripheral, but not central. Additionally, I. latifolia (50 and 100 µg/mL) and 3,5-di-caffeoyl quinic acid methyl ester (5 µM) isolated from I. latifolia as an active compound significantly inhibited LPS-induced NO production and mRNA expression of the pro-inflammatory mediators, iNOS and COX-2, and the pro-inflammatory cytokines, IL-6 and IL-1β, in RAW 264.7 macrophages. These results suggest that I. latifolia can produce antinociceptive effects peripherally, but not centrally, via anti-inflammatory activity and supports a possible use of I. latifolia to treat pain and inflammation.

Acetic Acid , Animals , Cyclooxygenase 2 , Cytokines , Ibuprofen , Ilex , In Vitro Techniques , Inflammation , Interleukin-6 , Macrophages , Mice , Nitric Oxide , Nociception , Pain Measurement , Quinic Acid , RNA, Messenger
Article in English | WPRIM | ID: wpr-739661


Dysregulation of excitatory neurotransmission has been implicated in the pathogenesis of neuropsychiatric disorders. Pharmacological inhibition of N-methyl-D-aspartate (NMDA) receptors is widely used to model neurobehavioral pathologies and underlying mechanisms. There is ample evidence that overstimulation of NMDA-dependent neurotransmission may induce neurobehavioral abnormalities, such as repetitive behaviors and hypersensitization to nociception and cognitive disruption, pharmacological modeling using NMDA has been limited due to the induction of neurotoxicity and blood brain barrier breakdown, especially in young animals. In this study, we examined the effects of intraperitoneal NMDA-administration on nociceptive and repetitive behaviors in ICR mice. Intraperitoneal injection of NMDA induced repetitive grooming and tail biting/licking behaviors in a dose- and age-dependent manner. Nociceptive and repetitive behaviors were more prominent in juvenile mice than adult mice. We did not observe extensive blood brain barrier breakdown or neuronal cell death after peritoneal injection of NMDA, indicating limited neurotoxic effects despite a significant increase in NMDA concentration in the cerebrospinal fluid. These findings suggest that the observed behavioral changes were not mediated by general NMDA toxicity. In the hot plate test, we found that the latency of paw licking and jumping decreased in the NMDA-exposed mice especially in the 75 mg/kg group, suggesting increased nociceptive sensitivity in NMDA-treated animals. Repetitive behaviors and increased pain sensitivity are often comorbid in psychiatric disorders (e.g., autism spectrum disorder). Therefore, the behavioral characteristics of intraperitoneal NMDA-administered mice described herein may be valuable for studying the mechanisms underlying relevant disorders and screening candidate therapeutic molecules.

Adult , Animals , Autistic Disorder , Blood-Brain Barrier , Cell Death , Cerebrospinal Fluid , Grooming , Humans , Injections, Intraperitoneal , Mass Screening , Mice , Mice, Inbred ICR , N-Methylaspartate , Neurons , Nociception , Pathology , Synaptic Transmission , Tail
Article in English | WPRIM | ID: wpr-761789


The lamina II, also called the substantia gelatinosa (SG), of the trigeminal subnucleus caudalis (Vc), is thought to play an essential role in the control of orofacial nociception. Glycine and serotonin (5-hydroxytryptamine, 5-HT) are the important neurotransmitters that have the individual parts on the modulation of nociceptive transmission. However, the electrophysiological effects of 5-HT on the glycine receptors on SG neurons of the Vc have not been well studied yet. For this reason, we applied the whole-cell patch clamp technique to explore the interaction of intracellular signal transduction between 5-HT and the glycine receptors on SG neurons of the Vc in mice. In nine of 13 neurons tested (69.2%), pretreatment with 5-HT potentiated glycine-induced current (I(Gly)). Firstly, we examined with a 5-HT₁ receptor agonist (8-OH-DPAT, 5-HT(1/7) agonist, co-applied with SB-269970, 5-HT₇ antagonist) and antagonist (WAY-100635), but 5-HT₁ receptor agonist did not increase IGly and in the presence of 5-HT₁ antagonist, the potentiation of 5-HT on I(Gly) still happened. However, an agonist (α-methyl-5-HT) and antagonist (ketanserin) of the 5-HT₂ receptor mimicked and inhibited the enhancing effect of 5-HT on I(Gly) in the SG neurons, respectively. We also verified the role of the 5-HT₇ receptor by using a 5-HT₇ antagonist (SB-269970) but it also did not block the enhancement of 5-HT on I(Gly). Our study demonstrated that 5-HT facilitated I(Gly) in the SG neurons of the Vc through the 5-HT₂ receptor. The interaction between 5-HT and glycine appears to have a significant role in modulating the transmission of the nociceptive pathway.

Animals , Glycine , Mice , Neurons , Neurotransmitter Agents , Nociception , Patch-Clamp Techniques , Receptors, Glycine , Serotonin , Signal Transduction , Substantia Gelatinosa
Rev. habanera cienc. méd ; 17(3): 386-395, mayo.-jun. 2018. graf
Article in Spanish | LILACS, CUMED | ID: biblio-978538


Introducción: Entre el lugar del daño tisular y la percepción del dolor, ocurre una serie de eventos electroquímicos que se conocen como nocicepción y comprenden cuatro procesos neurofisiológicos conocidos como: transducción, transmisión, modulación y percepción. Objetivo: Aportar información actualizada sobre las regiones del encéfalo vinculadas a la interpretación del dolor. Material y Método: Se realizó una revisión bibliográfica, con vistas a esclarecer la interpretación de la señal nociceptiva. Se consultaron treinta y cinco artículos científicos, se determinó escoger un total de veintinueve por su relación directa con el propósito de la búsqueda, veintitrés de los cuales corresponden a los últimos 5 años publicados en revistas internacionales y nacionales. Desarrollo: Los axones nociceptivos se clasifican como A δ; y C, participan en la conducción de los potenciales de acción de la periferia al sistema nervioso central. La transmisión de la señal en forma de potenciales de acción se descodifica en áreas relacionadas con aspectos cognoscitivos, afectivo, emocional y conductual del dolor. Este disímil conjunto de estructuras se reconoce en la actualidad como matriz encefálica del dolor. Conclusiones: La matriz del dolor, corresponde a áreas encefálicas como las cortezas somestésicas SI y SII, implicadas en el aspecto discriminativo del dolor. La corteza cingulada anterior y la corteza insular están asociadas al componente afectivo emocional del dolor(AU)

Introduction: A series of electrochemical events called nociception occur between the tissue damage and the perception of pain. They include four neurophysiological processes known as: transduction, transmission, perception, and modulation. Objective: To provide up-to-date information about the regions of the brain involved with the interpretation of pain. Material and Method: A bibliographic review was carried out with the aim of clarifying the interpretation of the nociceptive signal. Thirty-five scientific articles were consulted, and a total of twenty-nine were chosen due to their direct relationship with the aim of the search, twenty-three of which correspond to the last five years of publication in national and international journals. Development: Nociceptive axons are classified as Aδ; and C, and participate in the conduction of action potential of the peripheral nervous system (PNS). The transmission of the signal in the form of action potential is decoded in areas related to cognoscitive, affective, and emotional aspects, and the behavioral area of pain. This dissimilar group of structures is recognized at present as the brain matrix of pain. Conclusions: The pain matrix corresponds to brain areas such as SI and SII somatosensory cortices, implied in the discriminative aspect of pain. Both the anterior cingulate cortex (ACC) and the anterior insular cortex (AIC) are associated with the emotional and affective component of pain(AU)

Humans , Male , Female , Pain , Brain , Pain Perception/physiology , Nociception/physiology
Neuroscience Bulletin ; (6): 321-329, 2018.
Article in English | WPRIM | ID: wpr-777054


Accumulating evidence suggests that obesity is associated with chronic pain. However, whether obesity is associated with acute inflammatory pain is unknown. Using a well-established obese mouse model induced by a high-fat diet, we found that: (1) the acute thermal pain sensory threshold did not change in obese mice; (2) the model obese mice had fewer nociceptive responses in formalin-induced inflammatory pain tests; restoring the obese mice to a chow diet for three weeks partly recovered their pain sensation; (3) leptin injection induced significant phosphorylation of STAT3 in control mice but not in obese mice, indicating the dysmodulation of topical leptin-leptin receptor signaling in these mice; and (4) leptin-leptin receptor signaling-deficient mice (ob/ob and db/db) or leptin-leptin receptor pathway blockade with a leptin receptor antagonist and the JAK2 inhibitor AG 490 in wild-type mice reduced their nociceptive responses in formalin tests. These results indicate that leptin plays a role in nociception induced by acute inflammation and that interference in the leptin-leptin receptor pathway could be a peripheral target against acute inflammatory pain.

Animals , Diet, High-Fat , Inflammation , Metabolism , Leptin , Metabolism , Pharmacology , Male , Mice , Mice, Inbred C57BL , Nociception , Physiology , Nociceptive Pain , Metabolism , Obesity , Metabolism , Pain Measurement , Pain Threshold , Physiology , Receptors, Leptin , Metabolism , Signal Transduction , Physiology
Article in English | WPRIM | ID: wpr-739425


BACKGROUND: Curcumin is traditionally used as an herbal medicine. We explored the efficacy of intrathecal curcumin in relieving both postoperative and inflammatory pain and elucidated the mechanisms of action of curcumin interacting with γ-aminobutyric acid (GABA) and opioid receptors at the spinal level. METHODS: Experimental pain was induced in male Sprague-Dawley rats via paw incision or injection of intraplantar carrageenan. After examination of the effects of intrathecal curcumin on the pain, GABA and opioid receptor antagonists were intrathecally administered to explore the involvement of GABA or opioid receptors on the effect of curcumin. Additionally, the expression levels of the GABA and opioid receptors were assessed. RESULTS: Intrathecal curcumin reduced the withdrawal threshold of both incisional surgery- and carrageenan injection-induced nociception. Intrathecal GABA and opioid receptor antagonists reversed the curcumin-mediated antinociception. Incisional surgery decreased the levels of the GABA receptors mRNA, but little changed the levels of the opioid receptors mRNA. Carrageenan injection increased the levels of the opioid receptors mRNA, but not the GABA receptors mRNA levels. Intrathecal curcumin increased or decreased the levels of GABA receptors mRNA and opioid receptors mRNA in the spinal cords of incised or carrageenan-injected rats, respectively. CONCLUSIONS: Intrathecal curcumin was effective to postoperative and inflammatory pain and such antinociception of curcumin was antagonized by both GABA and opioid receptor antagonists. Also, intrathecal curcumin altered the levels of GABA and opioid receptors. Thus, spinal GABA and opioid receptors may, respectively, be directly or indirectly involved when curcumin alleviates postoperative and inflammatory pain.

Animals , Carrageenan , Curcumin , gamma-Aminobutyric Acid , Herbal Medicine , Humans , Male , Narcotic Antagonists , Nociception , Rats , Rats, Sprague-Dawley , Receptors, GABA , Receptors, Opioid , RNA, Messenger , Spinal Cord
Braz. j. med. biol. res ; 51(11): e7356, 2018. tab, graf
Article in English | LILACS | ID: biblio-951728


Essential oils (EO) are volatile liquids responsible for the aroma of plants. Pterodon polygalaeflorus seeds have received widespread use in folk medicine for the treatment of inflammatory diseases. For this reason and because Pterodon polygalaeflorus seeds have great EO content, which is frequently pharmacologically active, the present study aimed to evaluate the antinociceptive effect of EO from Pterodon polygalaeflorus (EOPPgfl) and its acute toxic effects. The EEOPPgfl sample, which was extracted by steam distillation of the seeds, had a yield of 2.4% of the seeds weight and had, as major constituents, beta-elemene (48.19%), trans-caryophyllene (19.51%), and epi-bicyclosesquiphellandrene (12.24%). The EOPPgfl sample showed mild acute toxicity and its calculated median lethal dose (LD50) was 3.38 g/kg. EOPPgfl (20-60 mg/kg) showed antinociceptive activity as evidenced by several tests and inhibited writhing induced by acetic acid. The maximum effect was obtained with the 30 mg/kg dose and at 60 min after its administration. EOPPgfl also decreased formalin-induced nociception, as verified by the inhibition of the first and second phase of the formalin test. At 30 mg/kg, EOPPgfl also decreased thermally stimulated nociception. Nociception may be related to inflammatory and antiedematogenic activity and at doses ranging 10-100 mg/kg, EOPPgfl blocked dextran- and carrageenan-induced edema. The results demonstrated that EOPPgfl presented, at doses approximately 100 times smaller than LD50, an antinociceptive effect that probably was due to anti-inflammatory activities.

Animals , Rabbits , Plant Oils/pharmacology , Oils, Volatile/pharmacology , Plant Extracts/pharmacology , Nociception/drug effects , Analgesics/pharmacology , Fabaceae/chemistry , Seeds/chemistry , Time Factors , Pain Measurement , Random Allocation , Reproducibility of Results , Treatment Outcome , Anti-Inflammatory Agents/pharmacology
Pesqui. vet. bras ; 37(8): 835-839, Aug. 2017. tab, graf
Article in Portuguese | LILACS, VETINDEX | ID: biblio-895502


O objetivo deste estudo foi identificar cães com doença do disco intervertebral toracolombar (Hansen tipo I) submetidos ao tratamento cirúrgico em um serviço de rotina em neurologia de um hospital veterinário universitário no período de 2006 a 2014, e obter informações a respeito da idade, do sexo, da raça, local da extrusão, interpretação da mielografia, avaliação dos graus de disfunção neurológica, recuperação funcional desses cães e observar a ocorrência de recidiva dos sinais clínicos da doença. A raça mais frequente foi Dachshund (69%), seguida dos cães sem raça definida (14,5%). Os locais mais afetados foram entre T12-T13 (31,9%) e L1-L2 (19,1%). Dos 110 cães, 74 (67,3%) tiveram melhora dos sinais clínicos após o procedimento cirúrgico, sendo 54 (49,1%) considerados satisfatórios e 20 (18,2%), parcialmente satisfatórios. Destes cães, seis (8,1%) cães estavam em grau II, 19 (25,7%) em grau III, 35 (47,3%) em grau IV e 14 (18,9%) em grau V. Pode-se concluir que o tratamento cirúrgico promove recuperação funcional satisfatória na maioria dos cães com extrusão de disco toracolombar. O prognóstico para recuperação funcional após o tratamento cirúrgico é tanto melhor quanto menor for o grau de disfunção neurológica e o percentual de recidiva é baixo em animais submetidos a este tipo de terapia.(AU)

The aim of this study was to identify dogs with thoracolumbar intervertebral disc disease (Hansen type I) submitted for surgical treatment on a routine service in neurology in a university veterinary hospital in 2006-2014, and to get information about age, sex, breed, site of extrusion, interpretation of myelography, evaluation of the degree of neurological dysfunction, functional recovery of these dogs, and to verify the recurrence of clinical signs of disease. The most common breed was Dachshund (69%), followed by mixed breed (14.5%). The most affected sites were between T12-T13 (31.9%) and L1-L2 (19.1%). Of the 110 dogs, 74 (67.3%) improved clinical signs after surgery, 54 (49.1%) satisfactory and 20 (18.2%), in part satisfactory. From these dogs, six (8.1%) dogs were in grade II, 19 (25.7%) in grade III, 35 (47.3%) in grade IV, and 14 (18.9%) in grade V. It can be concluded that satisfactory surgical treatment promotes functional recovery in most dogs with thoracolumbar disk extrusion. The prognosis for functional recovery after surgical treatment is better the lower the degree of neurological dysfunction and the recurrence percentage is lower in dogs subjected to this type of therapy.(AU)

Animals , Dogs , Decompression, Surgical/veterinary , Intervertebral Disc Degeneration/veterinary , Nociception , Intervertebral Disc/surgery , Spinal Cord Diseases/veterinary , Hernia/veterinary
Pesqui. vet. bras ; 37(8): 853-858, Aug. 2017. tab
Article in Portuguese | LILACS, VETINDEX | ID: biblio-895505


Fraturas e luxações vertebrais (FLV) toracolombares estão dentre as afecções neurológicas mais frequentes na neurologia veterinária. São um dos distúrbios mais graves e desafiadores, devido ao elevado risco de paralisia permanente, levando muitos animais a serem submetidos à eutanásia, devido ao prognóstico desfavorável nos animais que perderam a nocicepção. Objetivou-se descrever as bases neurofisiológicas responsáveis pelo desenvolvimento do caminhar espinal e analisar, em 37 cães acometidos por FLV toracolombares, os dados referentes à taxa de recuperação dos animais com e sem nocicepção. Naqueles sem nocicepção, analisou-se ainda a frequência dos animais que desenvolveram caminhar espinal e o período médio para seu aparecimento. Em relação ao grau da lesão a as taxas de recuperação, 14/37 animais (37,8%) possuíam nocicepção, no qual a taxa de recuperação da deambulação voluntaria e das funções viscerais foi de 100%. Enquanto que 23/37 animais (62,1%) perderam a nocicepção, no qual nenhum recuperou a deambulação voluntária, ocorrendo morte por causas diversas em sete destes. Dos 16 animais sem nocicepção sobreviventes e que foram submetidos ao tratamento conservativo ou cirúrgico, cinco (31,25%) readquiriram a capacidade de caminhar (tempo médio de 115 dias) sem recuperar a nocicepção, sendo esta deambulação involuntária atribuída ao caminhar espinal. De acordo com os resultados desta pesquisa, o parâmetro isolado da perda da nocicepção não deve desencorajar a realização da terapia, pois em cães paraplégicos com FLV toracolombares, há possibilidade de ocorrer desenvolvimento de deambulação involuntária.(AU)

Thoracolumbar vertebral fractures and luxations (VFL) are one of the most common neurological disorders in veterinary neurology and one of the most serious and challenging disorders due to the high risk of permanent paralysis, leading many dogs to be euthanized without treatment due to the reports of unfavorable prognosis about ambulation in animals that lost nociception. This study aimed to describe the neurophysiologic bases responsible for the development of the spinal walking and examine in 37 dogs affected with thoracolumbar VFL, data relating to the recovery rate of animals with and without nociceptionIn those without nociception was analyzed the frequency of the spinal walking animals that developed for its appearance, and the average period was established. Regarding the degree of injury to recovery rates, 14/37 dogs (37.8%) had nociception, in which the rate of recovery of voluntary ambulation was 100%. While 23/37 dogs (62.1%) lost the nociception, where no voluntary ambulation was regained ambulation, occurred death from various causes in seven of these. From 16 dogs without nociception and survivors who underwent conservative or surgical treatment, five (31.25%) regained the ability to walk without regaining nociception; this was attributed to spinal walking, where the average time for their development was 115 days. According to the results of this study, the single parameter of loss of the nociception should not discourage the therapy, as paraplegic dogs with thoracolumbar VFL can develop involuntary ambulation.(AU)

Animals , Dogs , Paraplegia/veterinary , Spinal Fractures/therapy , Spinal Fractures/veterinary , Nociception , /veterinary , Thoracic Injuries/veterinary