Pain Patterns of the Temporomandibular Joint Dysfunction and Implications of Stress-Related Behaviors: A Pilot Study / Patrones de Dolor de la Disfunción de la Articulación Temporomandibular e Implicaciones de los Comportamientos Relacionados con el Estrés: Un Estudio Piloto

SUMMARY: Temporomandibular joint dysfunction interferes with the quality of life and activities of daily living among patients. The symptoms of temporomandibular dysfunction, including pain and clicking and popping sounds, are worsened during stressful events, and patients report increased pain around the temporomandibular joint. Stress-related behaviors, such as teeth clenching and teeth grinding, are commonly reported as increasing during stress. The prevalence of temporomandibular dysfunction and stress-related behaviors is reported differently in the literature. Stress in higher education is common. The purpose of this pilot study was to investigate the prevalence of temporomandibular joint dysfunction and stress-related behaviors among staff members at a local University. The study also sought to explore pain patterns described by people experiencing temporomandibular joint dysfunction and the relationship between stress-related behaviors and pain symptoms experienced. Further, the impact of stress on symptoms experienced by people with temporomandibular dysfunction was investigated in this pilot study.

La disfunción de la articulación temporomandibular interfiere con la calidad de vida y las actividades de la vida diaria entre los pacientes. Los síntomas de la disfunción temporomandibular, incluidos el dolor y los chasquidos, empeoran durante los eventos estresantes, y los pacientes informan un aumento del dolor alrededor de la articulación temporomandibular. Los comportamientos relacionados con el estrés, como apretar y rechinar los dientes, suelen aumentar durante el estrés. La prevalencia de la disfunción temporomandibular y los comportamientos relacionados con el estrés se informa de manera diferente en la literatura. El estrés en la educación superior es común. El propósito de este estudio piloto fue investigar la prevalencia de la disfunción de la articulación temporomandibular y los comportamientos relacionados con el estrés entre los miembros del personal de una universidad local. El objetivo del estudio además fue explorar los patrones de dolor descritos por personas que experimentan disfunción de la articulación temporomandibular y la relación entre los comportamientos relacionados con el estrés y los síntomas de dolor experimentados. Además, en este estudio piloto se investigó el impacto del estrés en los síntomas que experimentan las personas con disfunción temporomandibular.

Effect of esketamine on efficacy of postoperative patient-controlled intravenous analgesia in patients with moderate central sensitization undergoing high tibial osteotomy / 中华麻醉学杂志

Objective:To evaluate the effect of esketamine on the efficacy of postoperative patient-controlled intravenous analgesia (PCIA) in the patients with moderate central sensitization undergoing high tibial osteotomy.Methods:Fifty-four patients of both sexes with moderate central sensitization, aged 45-64 yr, with body mass index of 18.0-32.5 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective high tibial osteotomy, were divided into 2 groups ( n=27 each) using a random number table method: control group (group C) and esketamine group (group ES). Ultrasound-guided femoral nerve block was performed with 0.5% ropivacaine 30 ml on the operated side at 30 min before induction of anesthesia.In C and ES groups, midazolam 0.1 mg/kg, sufentanil 0.2 μg/kg, propofol 1.5 mg/kg, and cisatracurium besilate 0.15 mg/kg were intravenously injected in turn during induction of anesthesia, and in addition esketamine hydrochloride 0.5 mg/kg was injected in ES group, and the equal volume of 0.9% sodium chloride was injected in C group, and then a laryngeal mask airway was placed.Anesthesia was maintained with intravenous infusion of remifentanil 0.1-0.3 μg·kg -1·min -1 and propofol 4-6 mg·kg -1·h -1.Esketamine hydrochloride 0.2 mg/kg was intravenously injected once every 20 min until 30 min before the end of operation in ES group, the equal volume of 0.9% sodium chloride was injected according to the amount of esketamine hydrochloride injected for the same body weight at the same time point in C group, and additional cisatracurium besilate was administered intermittently according to the degree of muscle relaxation.Intraoperative BIS values were maintained at 40-60.Postoperative PCIA was performed, and the patient was admitted to the post-anesthesia care unit.When the efficacy of PCIA was not good, ketorolac tromethamine 30 mg was intravenously injected for rescue analgesia.The intraoperative consumption of remifentanil and propofol and emergence time in the anesthesia recovery room were recorded.The pressing times of PCA and the number of rescue analgesia in each group were recorded within 2 days after operation.The Chinese Richards-Campbell Sleep Questionnaire was used to assess the nighttime sleep quality on the night of surgery and 1 and 2 days after surgery.The Chinese Quality of Recovery was used to assess the early recovery quality at 1 and 2 days after surgery.The first postoperative off-bed time and first walked distance were recorded.The adverse reactions were recorded. Results:Compared with group C, the consumption of remifentanil and propofol was significantly reduced, the emergence time in the anesthesia recovery room was prolonged, the pressing times of PCA and the number of rescue analgesia were decreased within 2 days after operation, the quality of nighttime sleep was improved on the night of surgery and 1 and 2 days after operation, the quality of early recovery on 1 and 2 days after operation was increased, the first postoperative off-bed time was shortened, the first walked distance was prolonged, and the incidence of postoperative adverse effects was decreased in group ES ( P<0.05). Conclusions:Esketamine can enhance the efficacy of postoperative PCIA in the patients with moderate central sensitization undergoing high tibial osteotomy.

The genetic influence of the brain-derived neurotrophic factor Val66Met polymorphism in chronic low back pain

Abstract Background: The Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene is a potential biomarker of vulnerability to pain. Thus, the present study aimed to investigate the association of this polymorphism with clinical and biopsychosocial factors in patients with chronic low back pain (CLBP). Methods: A total of 107 individuals with CLBP answered questionnaires that were validated and adapted for the Brazilian population, including the Brief Inventory of Pain, the Central Sensitization Inventory, the Roland Morris Disability Questionnaire, the Tampa Scale for Kinesiophobia, the Pain Catastrophizing Scale, the Survey of Pain Attitude-Brief, and the Hospital Anxiety and Depression Scale. All of the subjects were genotyped for the BDNF Val66Met polymorphism. Results: The sample showed moderate scores of disability, central sensitization, and kinesiophobia, in addition to mild anxiety, hopelessness, and ruminant thoughts. No significant association was observed between the Val66Met polymorphism and the variables analyzed. Besides, there was no relationship between the BDNF Val66Met polymorphism with CSI, catastrophization, or disabilities that were generated by CLBP. Conclusions: The results showed that the Val66Met polymorphism of the BDNF gene was not associated with clinical and biopsychosocial characteristics of CLBP in the sample studied.

Prokineticin 2 mediates peripheral and central sensitization of somatic pain / 药学实践杂志

Prokineticin 2 (PK2) is a newly discovered chemokine, which participates in various physiological functions of the body by binding to receptors PKR1 and PKR2. PK signaling pathway is a newly discovered important regulatory pathway for the occurrence and maintenance of pain after tissue injury and nerve injury in recent years. It plays a key role in regulating injury-related nociceptive events and is a potential therapeutic target for many diseases. The activation of PKRs can induce pain sensation and participate in the sensitivity of pain receptors to different stimuli. The PK system (PKs and PKRs) is an important link involved in inflammation and pain transmission in immune cells. PK2 is involved in the regulation of pain perception by activating PKR1 and PKR2 on primary sensory neurons. In rat primary sensory neurons, PK2 also enhances gated ion channel current through the PKC signaling pathway, inhibits GABA-activated currents, and sensitizes purine nucleotide P2 receptor (P2X). This paper reviews the research progress of PK2 in physical pain. We hope to find new drugs for the treatment of inflammatory pain that target the PKs signaling pathway in future studies.

Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain

BACKGROUND: To investigate the thalamic neurotransmitters and functional connections in the development of chronic constriction injury (CCI)-induced neuropathic pain. METHODS: The paw withdrawal threshold was measured by mechanical stimulation the right hind paw with the von frey hair in the rats of CCI-induced neuropathic pain. The N-acetylaspartate (NAA) and Glutamate (Glu) in thalamus were detected by magnetic resonance spectrum (MRS) process. The thalamic functional connectivity with other brain regions was scanned by functional magnetic resonance image (fMRI). RESULTS: The paw withdrawal threshold of the ipsilateral side showed a noticeable decline during the pathological process. Increased concentrations of Glu and decreased levels of NAA in the thalamus were significantly correlated with mechanical allodynia in the neuropathic pain states. The thalamic regional homogeneity (ReHo) decreased during the process of neuropathic pain. The functional connectivity among the thalamus with the insula and somatosensory cortex were significantly increased at different time points (7, 14, 21 days) after CCI surgery. CONCLUSION: Our study suggests that dynamic changes in thalamic NAA and Glu levels contribute to the thalamic functional connection hyper-excitation during CCI-induced neuropathic pain. Enhanced thalamus-insula functional connection might have a significant effect on the occurrence of neuropathic pain.

Expression of glycine receptor α3 subunit in neuropathic and inflammatory central pain sensitization

INTRODUCTION: Increasing evidence suggests that changes in the balance of excitatory/inhibitory neurotransmission are involved in the development of the majority of chronic pain forms. In this context, impairment in glycine mediated inhibitory neurotransmission is thought to play a critical role in the disinhibition that accounts for the development and maintenance of central pain hypersensitivity. AIMS: The goal of this study was to evaluate the Glycine Receptor α3 subunit (α3GlyR) expression in neuropathic (Chronic Constriction Injury, CCI) and inflammatory (Zymosan A injected) animal models of chronic pain. RESULTS AND CONCLUSION: RT-qPCR analysis of spinal cord samples showed that glra3 gene expression does not change after 3 days of CCI and 4 hours of Zymosan A injection. However, we found that protein levels evaluated by Western blot increased after inflammatory pain. These data suggest that central sensitization is differentially regulated depending on the type of pain. α3GlyR protein expression plays an important role in the first step of inflammatory pain establishment.

Estenosis de canal lumbar: comorbilidades y análisis morfométrico / Lumbar canal stenosis: comorbidities and morphometric analysis

Introducción: La Estenosis de Canal Lumbar (ECL) refiere al estrechamiento central del canal raquídeo, recesos laterales o agujeros de conjunción. Comúnmente, causa lumbalgia crónica en quienes la padecen afectando gravemente su calidad de vida. Sin embargo, su pronóstico, incidencia sigue siendo incierta en nuestra región. Objetivo: El presente trabajo tiene como propósito, determinar la frecuencia local de la ECL y su relación con distintos parámetros morfométricos, comorbilidades y el cuestionario CSI. Material y Método: Se realizó un estudio prospectivo, analítico, asociativo y de corte transversal de las consultas atendidas por el servicio de Neurocirugía del Hospital Enrique Vera Barros de la ciudad de La Rioja Capital, Argentina durante el período agosto-diciembre 2018. Se aplicó el cuestionario "Central Sensitization Inventory" (CSI). Resultados: La ECL fue diagnosticada en 42.9% de hombres que consultaron por lumbalgia y en el 33.3% en el caso de las mujeres. La media de la edad de los pacientes con ECL fue 57 años. El 100% de pacientes presentaron comorbilidades, siendo la más prevalente la artrosis. La dorsopatía más asociada fue la Hernia de Disco Lumbar (27.3%). La intensidad del dolor y los diámetros antero-posterior (DAP) y laterales (DL), fueron inversamente significativos (DAP= -,813 p=0,09; DL= -,967 p=0,007). El puntaje en el CSI fue significativamente mayor en pacientes con ECL (37 vs. 24,62 pts.) (p=,028). Finalmente, la correlación entre los DAP y DL con el puntaje del CSI mostró una correlación inversa (DAP= -,733 p>0,05; DL= -,639 p>0,05). Conclusión: En nuestro estudio encontramos que la prevalencia de ECL es más alta en hombres de edad media y que presentan comorbilidades asociadas, además el análisis morfométrico del canal raquídeo se asocia con la intensidad del dolor y el puntaje en el CSI. Por lo cual estas variables podrían ser utilidad clínica al momento de decidir el manejo adecuado para pacientes con ECL.

Introduction: Lumbar Spinal Stenosis (LSS) anatomically can involve the central canal, lateral recess, neural foramen or any combination of these locations. Although, LSS has been consider a common cause of chronic low back pain. Only few studies had explored the prevalence, incidence and associated variables in non-Caucasian populations. Therefore, the aim of this study is to determine the local frequency of LSS and its relationship with different morphometric parameters, comorbidities and the Central Sensitization Inventory (CSI). Methods: A prospective, analytical, associative and cross-sectional study of patients With LSS by single academic center was carried out. Diagnoses were done by clinical and MRI assessment. Results: LSS was diagnosed in 42.9% of males and 33.3% of females who consulted for low back pain. The average age of the patients with LSS was 57 years. 100% of LSS patients presented comorbidities, the most prevalent being osteoarthritis. Lumbar Disc Hernia was associated in 27.3% of patients with LSS. Pain intensity was inversely correlated (AP= -,813 p=0,09; L= -,967 p=0,007) with anteroposterior (AP), and lateral (L) diameters. The score in the CSI was significantly higher in patients with LSS (37 vs. 24,62 pts.) (p=,028). Finally, the correlation between the AP and L diameters with the CSI score was inverse (AP= -,733 58 p>0,05; L= -,639 p>0,05). Conclusions: In our study, we found that the prevalence of LSS is higher in middle-aged men with associated comorbidities. In addition, morphometric analysis of the spinal canal is associated with pain intensity and CSI scores. Therefore, these variables could be clinical applicable when deciding the appropriate management for patients with LSS.

TNF-α/TNFR1 Signaling is Required for the Full Expression of Acute and Chronic Itch in Mice via Peripheral and Central Mechanisms / 神经科学通报·英文版

Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha (TNF-α) and its receptors TNF receptor subtype-1 (TNFR1) and TNFR2 in acute and chronic itch in mice. Compared to wild-type (WT) mice, TNFR1-knockout (TNFR1-KO) and TNFR1/R2 double-KO (DKO), but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine (CQ). Application of the TNF-synthesis inhibitor thalidomide and the TNF-α antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia (DRG) and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etanercept and in TNFR1/R2 DKO mice. Dry skin induced TNF-α expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-α/TNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be beneficial for chronic itch treatment.

Síndrome de fatiga / Fatigue syndrome

ResumenEl síndrome de fatiga crónica es una patología que se caracteriza por fatiga intensa de como mínimo seis meses de duración, que se acompaña de otros síntomas y que en ocasiones podría ser tan intenso que causa la disminución de las actividades cotidianas del individuo que lo padece. El comienzo de los síntomas puede ser repentino o también de forma paulatina, muchas veces las personas recuerdan el momento en que comenzó y el principio de estos puede ser un cuadro similar a una gripe. A continuación, se hará una revisión bibliográfica sobre los principales aspectos de esta enfermedad, causa, criterios diagnósticos y tratamiento.

AbstractChronic fatigue syndrome is a pathology characterized by intense fatigue of at least six months duration, which is accompanied by other symptoms and which at times could be so intense that it causes the daily activities of the individual suffering from it to diminish. The onset of symptoms may be sudden or also gradually, many times people remember the time they started and the beginning of these can be a flu-like four. Next, a bibliographic review will be done on the main aspects of this disease, cause, diagnostic criteria and treatment.

Analgesic effect of levo-corydalmine on neuropathic pain in rats and its mechanism / 中国药科大学学报

@#The aim of the present study was to investigate the effects of levo-corydalmine(l-CDL)on chronic constrictive injury(CCI)-induced neuropathic pain and central sensitization in spinal cord. The mechanical withdrawal threshold in rats was assessed by Von-Frey fibers and the thermal withdrawal latency was assessed by thermal stimulus apparatus. The level of phosphorylated N-methyl-D-aspartic acid receptor 1(NR1)in L4-L6 spinal cord was analyzed by immunoblotting and the expression of calcitonin gene related peptide(CGRP)and c-fos in spinal cord dorsal horn were analyzed by immunofluorescence. Results showed that l-CDL(7. 5, 15, 30 mg/kg, ig)inhibited CCI-induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. l-CDL significantly inhibited the up-regulation of p-NR1, c-fos and CGRP in CCI rats without tolerance. In conclusion, l-CDL has a good relieving effect on central sensitization in spinal cord, thus generating outstanding analgesic activity on CCI-induced neuropathic pain.

Content Validity and Test-Retest Reliability of the Gujarati Version of the Central Sensitization Inventory.

Background: Central sensitization (CS) is a state of heightened sensitivity of the central nervous system to both noxious and non-noxious stimuli. The Central Sensitization Inventory (CSI) is a sound screening tool to help clinicians to detect patients with CS. To date, no Gujarati version exists. Objectives: The aim of this study was to translate and cross-culturally adapt the CSI into Gujarati, and to check content validity, face validity, internal consistency, test-retest reliability, agreement and minimum detectable change (MDC) of CSI-G in chronic low back pain (CLBP) patients. Methods: Translation and cross-cultural adaptation of the original English version of the CSI-G was performed according to published guidelines. The content validity was ascertained by 23 healthcare professionals. The internal consistency, test-retest reliability, agreement and MDC was determined on CLBP patients (n=31) with a time interval of 7-days. Results: The content validity and Face validity was found to be excellent. The internal consistency was excellent (Cronbach’s α=0.914) and MDC was found to be 5.092 points. The test-retest reliability showed very high correlation in CLBP patients (ICC = 0.971). Conclusion: The original CSI was translated into Gujarati and did not pose any problems during data acquisition. The CSI-G seems to be reliable instruments to measure CS in Gujarati patients with CLBP. [Bid D NJIRM 2016; 7(5):18-24]

Central Sensitization In Chronic Low Back Pain: A Narrative Review.

Objective: The aim of this narrative review is to examine the available literature related to central sensitization (CS) and altered central pain processing in chronic low back pain (CLBP) patients. Methodology: Literature was searched using many electronic databases. Additionally, reference list of most prominent articles were searched to increase the search accuracy, as much as possible. Studies which are evaluating the concept of CS in conservatively treated CLBP patients were included. Results: Results of studies evaluating the responsiveness to various types of stimuli in CLBP patients are contradictory. Some studies in CLBP patients have showed increased pain responses after sensory stimulation of body parts outside the painful region, when some other studies report no differences between patients and healthy controls. Studies evaluating the integrity of the endogenous pain inhibitory systems describe unchanged activity of this descending inhibitory system. Conversely, studies examining brain structure and function in connection with experimentally induced pain provide initial proof for changed central pain processing in CLBP patients. Also inappropriate beliefs about pain, depression and/or pain catastrophizing, may lead to the development of CS. Conclusion: Most of the literatures suggest that the CNS becomes centrally sensitized in a subgroup of patients with CLBP. However, the significance of this involvement is just starting to become clearer. This could be an active topic of future research. More studies are necessary for providing definite evidence for the clinical importance of CS.

Peripheral and central sensitization / Sensibilização periférica e central

ABSTRACT BACKGROUND AND OBJECTIVES: Central sensitization is an important phenomenon for pain chronicity and is present in neuropathic pain. This study aimed at addressing some pathophysiological aspects of this phenomenon. CONTENTS: Some extra and intracellular aspects responsible for central sensitization genesis, especially phenotypic changes in plasticity of neurons involved in the process are described. CONCLUSION: Pain chronicity may result from changes in central nervous system neurons properties by the central sensitization phenomenon with constant changes in membrane excitability, inhibitory transmission reduction and increase in synaptic efficacy mediated by several convergent and divergent molecular mechanisms over a background of phenotypic and structural changes. Neuroplasticity deeply alters painful sensation, contributing for many clinical painful syndromes and may represent a major target for therapeutic intervention.

RESUMO JUSTIFICATIVA E OBJETIVOS: A sensibilização central é um fenômeno importante na cronificação da dor e presente na dor neuropática. O objetivo deste estudo foi abordar alguns aspectos fisiopatológicos deste fenômeno. CONTEÚDO: São descritos alguns aspectos extra e intracelular responsável pela gênese da sensibilização central, principalmente aspectos de alterações fenotípicas que ocorrem na plasticidade dos neurônios envolvidos no processo. CONCLUSÃO: A cronificação da dor pode surgir como resultado de alterações nas propriedades dos neurônios no sistema nervoso central pelo fenômeno da sensibilização central com constantes mudanças e alterações na excitabilidade da membrana, reduções na transmissão inibitória e aumento da eficácia sináptica, mediada por muitos convergentes e divergentes mecanismos moleculares sobre um fundo de modificações fenotípicas e alterações estruturais. A neuroplasticidade altera profundamente a sensação dolorosa, contribuindo para muitas síndromes clínicas da dor e pode representar um importante alvo para intervenção terapêutica.

Mechanisms of postoperative pain

Good pain control after surgery is important to facilitate overall recovery, improve patient satisfaction, decrease morbidity, and reduce health care cost. However, despite heightened awareness and development of new guidelines in recent decades, we have failed to make major improvements in postoperative pain control. Currently available analgesic therapies have limited efficacy, and pain after surgery continues to be a significant clinical problem. Our goal is to develop more effective and safer clinical strategies that will eliminate or greatly reduce postoperative pain, and a better understanding of the mechanisms of pain induced by surgery would be essential to achieve this goal. Evidence suggests that the pathophysiological mechanisms and optimal treatment of postoperative pain are different from many other painful conditions. Recognizing the necessity and importance of relevant pre-clinical models, we have developed and characterized rodent incision models that have close similarities to postoperative pain in patients. Previous studies have demonstrated the clinical relevance and translatability of these pre-clinical models of postoperative pain. In this review, we describe the rodent incision pain models, and summarized our current understanding of the mechanisms of postoperative pain, highlighting key findings from our previous studies using these models.

Trigeminal neuralgia: peripheral and central mechanisms / Neuralgia trigeminal: mecanismos periféricos e centrais

ABSTRACT BACKGROUND AND OBJECTIVES: Trigeminal neuralgia is one of the most common neuropathic pains that compromise head and neck. It manifests as shock or burning pain normally evoked by non-noxious facial stimulations. Its etiopathology is not totally understood, but it is known that different mechanisms contribute to the establishment and maintenance of pain. This study aimed to address current contexts of epidemiology, diagnosis, management and pathophysiological mechanisms underlying trigeminal neuralgia in peripheral and central nervous systems. CONTENTS: Inflammation and release of inflammatory mediators, neuropeptides and neurotrophic factors, as well as degenerative changes of nervous fibers caused by direct nervous injury are relevant peripheral mechanisms which lead to altered sensitivity of nociceptive neurons, development of spontaneous and exacerbated activity, allodynia and hyperalgesia. Among central mechanisms, exacerbated activation of central nociceptive neurons, neuroplasticity, changes in electrophysiological properties and neuronal hyperexcitability, in addition to changes in modulatory pain controls, lead to pain establishment and maintenance. CONCLUSION: Several mechanisms are involved in neuropathic pains, both in peripheral and central levels, although specific trigeminal neuralgia events are not totally described. Studies concerning its specific neurobiology are needed to understand functional and behavioral changes, which can contribute to trigeminal neuralgia clinical management and treatment.

RESUMO JUSTIFICATIVA E OBJETIVOS: A neuralgia do trigêmeo é uma das dores neuropáticas mais comumente encontradas na região de cabeça e pescoço e manifesta-se como crises de choque ou queimação geralmente desencadeadas por estímulos não dolorosos na região da face. A sua etiopatogenia não é totalmente conhecida, mas sabe-se que diversos mecanismos contribuem para seu estabelecimento. O objetivo deste estudo foi abordar os contextos atuais de epidemiologia, diagnóstico, tratamento e mecanismos fisiopatológicos subjacentes à neuralgia do trigêmeo nos sistemas nervoso periférico e central. CONTEÚDO: A inflamação e a liberação de mediadores inflamatórios, neuropeptídeos e fatores neurotróficos, assim como alterações degenerativas das fibras nervosas decorrentes da lesão nervosa direta são mecanismos periféricos relevantes que, em conjunto ou isoladamente, levam à sensibilidade alterada dos neurônios nociceptivos, com desenvolvimento de atividade espontânea e exacerbada e, consequentemente, dor espontânea e hiperalgesia. Dentre os mecanismos centrais, a ativação exacerbada de neurônios nociceptivos centrais, a neuroplasticidade, as alterações nas propriedades eletrofisiológicas e a hiperexcitabilidade neuronal, além das modificações nos controles modulatórios da dor, são eventos que levam à instalação e à manutenção da dor. CONCLUSÃO: Diversos mecanismos estão envolvidos nas dores neuropáticas, tanto a nível periférico quanto central, apesar dos eventos específicos da neuralgia do trigêmeo não estarem totalmente elucidados. Estudos que abordem a sua neurobiologia específica são necessários para a compreensão das alterações funcionais e comportamentais presentes, com claras repercussões no tratamento e manuseio clínico da neuralgia do trigêmeo.

Reduction of blood nitric oxide levels is associated with clinical improvement of the chronic pelvic pain related to endometriosis

The objective of this prospective study was to determine the plasma levels of nitric oxide (NO) in women with chronic pelvic pain secondary to endometriosis (n=24) and abdominal myofascial pain syndrome (n=16). NO levels were measured in plasma collected before and 1 month after treatment. Pretreatment NO levels (μM) were lower in healthy volunteers (47.0±12.7) than in women with myofascial pain (64.2±5.0, P=0.01) or endometriosis (99.5±12.9, P<0.0001). After treatment, plasma NO levels were reduced only in the endometriosis group (99.5±12.9 vs 61.6±5.9, P=0.002). A correlation between reduction of pain intensity and reduction of NO level was observed in the endometriosis group [correlation = 0.67 (95%CI = 0.35 to 0.85), P<0.0001]. Reduction of NO levels was associated with an increase of pain threshold in this group [correlation = -0.53 (-0.78 to -0.14), P<0.0001]. NO levels appeared elevated in women with chronic pelvic pain diagnosed as secondary to endometriosis, and were directly associated with reduction in pain intensity and increase in pain threshold after treatment. Further studies are needed to investigate the role of NO in the pathophysiology of pain in women with endometriosis and its eventual association with central sensitization.

Progress of pathogenesis of neuropathic pain / 国际儿科学杂志

Neuropathic pain arises as a direct consequence of a lesion or disease affects the somatosensory.Its symptoms include spontaneous,hyperalgesia and allodynia pain.Pain management is not satisfied through merely analgesics.To manage pain effectively is difficult in clinic.The paper is to review the progress of the mechanism of neuropathic pain.

Effect of intraoperative infusion of ketamine on remifentanil-induced hyperalgesia / 대한마취과학회지

BACKGROUND: Opioid induced hyperalgesia (OIH) is related with high opioid dosage, a long duration of opioid administration, and abrupt discontinuation of infused opioids in anesthetic settings. Ketamine is known to attenuate OIH efficiently, but methods of administration and methods to quantify and assess a decrease in OIH vary. We demonstrated the existence of remifentanil-induced hyperalgesia and investigated the ability of ketamine to attenuate OIH. METHODS: Seventy-five patients undergoing laparoscopic gynecologic surgery under remifentanil-based anesthesia were assigned to one of the following groups: (1) group RL (remifentanil 0.05 microg/kg/min), (2) group RH (remifentanil 0.3 microg/kg/min), or (3) group KRH (remifentanil 0.3 microg/kg/min + ketamine 0.5 mg/kg bolus with 5 microg/kg/min infusion intraoperatively). Desflurane was administered for maintenance of anesthesia to target bispectral index scores (40-60) and hemodynamic parameters (heart rate and blood pressure < +/- 20% of baseline values). All parameters related to OIH and its attenuation induced by ketamine were investigated. RESULTS: There was no significant difference among the three groups related to demographic and anesthetic parameters except the end-tidal concentration of desflurane. Additional analgesic consumption, numerical rating scale scores at 6 and 24 h, and cumulative fentanyl dose were significantly higher in group RH than in the other two groups. The value difference of the Touch-Test sensory evaluation was significantly higher negative in group RH than in the other two groups. CONCLUSIONS: Remifentanil-induced hyperalgesia is significantly attenuated by intraoperative bolus and infusion of ketamine. Ketamine also decreased tactile sensitization, as measured by Touch-Test sensory evaluation.

Fibromyalgia and the old dilemma: theory vs. practice

The objective of this article is to review some aspects of the fibromyalgia syndrome and its mechanisms of development. We also discuss how to go from preclinical research to clinical practice. Fibromyalgia is a clinical syndrome whose main features include diffuse musculoskeletal pain, fatigue, sleep disturbances, and cognitive disorders. Russell & Larsson (2009) proposed "pronociceptive" and "antinociceptive" systems under normal conditions. Functional pain states such as fibromyalgia are derived from central disturbances in pain processing. The association with anxiety and depression is a negative prognostic factor. Distress is an important part of its physiopathology. The concomitance of other functional syndromes is a rule. The already known etiopathogenic mechanisms of fibromyalgia can be applied in clinical practice for diagnosis and rational therapeutic approaches. Pharmacological but mainly nonpharmacological measures must be applied. Although much information still needs to be obtained, the clinician presently has sufficient tools for efficiently treating fibromyalgia patients. An important aspect is that such knowledge needs to reach primary care physicians because the prevalence of fibromyalgia does not allow all patients to be treated by specialists.

Changes of the level of phosphorelated ERK1/2 in the spinal trigeminal nucleus of migraine model rats / 中华行为医学与脑科学杂志

Objective To explore the role of ERK1/2 in the central pathogenesis of migraine.Methods Healthy adult male SD rats were randomly divided into five groups:normal group (group C),sham operation group(group C),migraine model group(group M),DMSO group (group D)and PD-98059group (PD group),with 12 rats in each group.The extracellular discharge frequency in the spinal trigeminal nucleus was recorded and ERK1/2 phosphorylation was tested.Results (1) The percentage of extracellular discharge frequency change:Two hours after treatment,the percentage of discharge frequency change was (325.9±47.32)％.The percentage of extracellula discharge frequency change in group M (325.9±47.3)％ was higher than that in group N (100.0± 0.0) ％ and group C(107.3± 16.4)％.There was no significant difference in the percentage of discharge frequency change between group D(319.3±42.5) ％ and group M (325.9±47.3) ％.The percentage of discharge frequency change in group PD(218.5±31.7)％ was lower than that in group M(325.9±47.3)％ and group D(319.3± 42.5)％.(2) ERK1/2 phosphorylation:the ERK1/2 phosphorylation in group M and group D was higher than that in group N and group C.There was no significant difference in ERK1/2 phosphorylation between group D and group M.The ERK1/2 phosphorylation in group PD was lower than the other four groups.Conclusion During the process of central sensitization to migraine,neuronal excitability and ERK1/2 phosphorylation were increased.ERK1/2 inhibitor (PD98059) reduced ERK1/2 phosphorylation and neuronal excitability.These indicated that ERK1/2 may play a role in central sensitization of migraine in rats.