The glossopharyngeal nerve (IX cranial nerve pair): anatomical considerations and neuralgia: literature review / O nervo glossofaringeo (IX par de nervo craniano): considerações anatômicas e neuralgia: revisão da literatura

The glossopharyngeal nerve (IX cranial nerve) is a mixed nerve, with both motor and sensory function. This relates to the tongue and pharynx. Glossopharyngeal neuralgia is a rare nervous neuropathy, with poristic, lancinating and paritary crises, usually unilateral. The aim of the study was to review the literature on glossopharyngeal neuralgia of the nerve (IX cranial nerve), highlighting the anatomical aspects of this nerve and the possible causes and complications of neuralgia as well as forms of treatment. A literature review was carried out in the international Pubmed database. The literature review included 72 articles from 2015 to 2021. The keywords used were: "anatomy of glossopharyngeal neuralgia". Of the 72 articles, 7 were used for this literature review. Uncommon as nervous/glossophingeal etiologies and pathologies are neurological abnormalities/neurovarises and pathologies are neurovascular/neurovariseal lesions. Pharmacological treatment approaches mentioned in the literature were therapy with antiepileptics and antidepressants such as carbamazepine and gabapentin; a microvascular decompression; and gamma knife radiosurgery(AU)

O nervo glossofaríngeo (IX par de nervo craniano) é um nervo misto, contendo função tanto motora como sensitiva. Este nervo relaciona-se com a língua e com a faringe. A neuralgia do nervo glossofaríngeo é uma neurapatia rara, sendo caracterizada por crises dolorosas, lancinantes e paroxísticas, geralmente unilaterais. O objetivo do estudo foi realizar uma revisão de literatura sobre a neuralgia do nervo glossofaríngeo (IX par de nervo craniano), destacando os aspectos anatômicos deste nervo e as possíveis causas e complicações da neuralgia bem como formas de tratamento. Foi realizada uma revisão da literatura na base de dados internacional Pubmed. A revisão da literatura incluiu 72 artigos no período de 2015 a 2021. As palavras-chave utilizadas foram: "anatomia da neuralgia do glossofaríngeo". Dos 72 artigos, 7 foram utilizados para esta revisão de literatura. Verificouse que a neuralgia do nervo glossofaríngeo é incomum e as etiologias mais encontradas foram compressão neurovascular/variações vasculares, patologias e traumas. As abordagens dos tratamentos mencionadas na literatura foram a terapia farmacológica da área com antiepilépticos e antidepressivos, como carbamazepina e gabapentina; a descompressão microvascular; e radiocirurgia com faca gama(AU)

A-waves associated are with neuropathic pain in leprosy

Introduction/Aims:The A-wave is a late response related either to demyelination or early axonal regeneration. It may be helpful in the evaluation of some peripheral neuropathies. In leprosy, previous studies suggested that A-waves could be a neurophysiological marker of pain in patients during reactions. Herein we have attempted to further assess the profile and clinical correlates of A-waves by exploring a large leprosy cohort. Methods: Between 2015 and 2018, 63 patients with leprosy (47 men and 16 women) had A-waves in nerve conduction studies and were included in this study. We included patients regardless of whether they were experiencing leprosy reactions ornot. We then compared clinical features in nerves with and without A-waves. Results:The mean age of study participants was 46.5 ± 12.3 years and most had borderline leprosy. From this cohort, we assessed separately 83 motor nerves that demonstrated A-waves (group A+) and 29 motor nerves that did not demonstrate A-waves (group A-). Neuropathic pain (NP) was found in 66 of 83 nerves in group A+,but only 5 of 29 in group A-(79.5 vs 17.2%,P< .001). In contrast, no significant between-group difference emerged regarding presence of reactions, sensory function (based on Semmes-Weinstein evaluations), or muscle strength. A-waves were found in nerves with neuropathic pain experiencing (39 of 66=59%) or not experiencing (27 of 66=41%) leprosy reactions. Discussion: These results show that A-waves are associated with neuropathic pain in leprosy patients, regardless of the nerves affected and the immune status (in reaction or not).

Dolor neuropático localizado / Localized neuropathic pain

Resumen El dolor neuropático localizado (DNL) es de origen periférico y se caracteriza por áreas circunscritas de dolor con sensibilidad anormal de la piel o síntomas espontáneos característicos de dolor neuropático, por ejemplo, dolor urente. Se debe resaltar que el DNL está confinado a un área específica no mayor a una hoja de papel tamaño carta. El DNL representa 60 % de las condiciones de dolor neuropático. No existe una única etiología. El abordaje diagnóstico es similar al de otros síndromes dolorosos neuropáticos. Se utilizan herramientas diagnósticas generales para evaluar las características clínicas. En la actualidad no existen guías específicas de manejo del DNL, por lo que se utilizan las guías para dolor neuropático en general. En las guías de la Sociedad Canadiense de Dolor se incluyen los tratamientos tópicos como parte de las estrategias de segunda línea. Pese a la falta de guías, los parches de lidocaína a 5 % y los parches de capsaicina a 8 % han demostrado ser efectivos en modelos de DNL.

Abstract Localized neuropathic pain (LNP) is of peripheral origin and is characterized by circumscribed areas of pain with abnormal skin sensitivity or spontaneous symptoms that are characteristic of neuropathic pain, e.g. burning pain. It should be noted that LNP is confined to a specific area no larger than a letter size sheet of paper. LNP accounts for 60 % of neuropathic pain conditions. There is no single etiology of LNP. The diagnostic approach is similar to that for other neuropathic pain syndromes. General diagnostic tools are used to assess clinical features. So far, there are no specific guidelines for the management of LNP; for this reason, guidelines for general neuropathic pain are used. Topical treatments are included as part of second-line strategies in the Canadian Pain Society guidelines. Despite the lack of guidelines, 5 % lidocaine patches and 8 % capsaicin patches have been proven effective in LNP models.

Tropomyosin receptor kinase B-mediated signaling in integration of neuropathic pain and obesity in diabetic polyneuropathy / Sinalização mediada pelo receptor de tropomiosina quinase tipo B na integração de dor neuropática e obesidade na polineuropatia diabética

ABSTRACT Objective: To assess the quantitative serum levels of tropomyosin receptor kinase receptor B, and to estimate its association with serum concentration of brain-derived neurotrophic factor and obesity in patients with painful and painless forms of diabetic polyneuropathy. Methods: We examined 70 patients with diabetic polyneuropathy with confirming peripheral nerve dysfunction by electroneuromyography and measuring of serum levels tropomyosin receptor kinase receptor B and brain-derived neurotrophic factor by enzyme immunoassay. Diabetic polyneuropathy was diagnosed using the modified Toronto Consensus (2011) criteria, while neuropathic pain was assessed using an 11-point Numerical Pain Rating Scale. The patients were divided into two groups according to presence or absence of neuropathic pain. Control Group consisted of 14 healthy persons. Results: The serum levels of tropomyosin receptor kinase receptor B and brain-derived neurotrophic factor in patients with diabetic polyneuropathy are significantly higher than healthy controls (p=0.000). Hyperexpression of brain-derived neurotrophic factor in serum was associated with painful form of diabetic polyneuropathy (R=0.392, p=0.012) and obesity (R=0.412, p=0.001). On the contrary high concentration of tropomyosin receptor kinase receptor B in serum associated with painless diabetic polyneuropathy by Pain DETECT (R=-0.354, p=0.015), low body weight (R=-0.354, p=0.015) and severe demyelization of nerve fibers (R=-0.574, p=0.001), indicated "non-working" receptor detected in serum. Conclusion: Tropomyosin receptor kinase receptor B signaling is involved in the modulation of neuropathic pain and obesity in diabetic polyneuropathy.

RESUMO Objetivo: Avaliar os níveis séricos quantitativos do receptor da tropomiosina quinase B, e estimar sua associação com os níveis séricos do fator neurotrófico derivado do cérebro e a obesidade, em pacientes com formas dolorosas e indolores de polineuropatia. Métodos: Examinamos 70 pacientes com polineuropatia diabética, com disfunção de nervo periférico confirmada por eletroneuromiografia e medida de níveis séricos do receptor da tropomiosina quinase B e do fator neurotrófico derivado do cérebro, por imunoensaio enzimático. Polineuropatia diabética foi diagnosticada através dos critérios modificados do Consenso de Toronto (2011), e a dor neuropática foi avaliada pela escala Numerical Pain Rating com 11 pontos. Os pacientes foram divididos em dois grupos, conforme presença ou ausência de dor neuropática. O Grupo Controle tinha 14 indivíduos saudáveis. Resultados: Os níveis séricos do receptor da tropomiosina quinase B e do fator neurotrófico derivado do cérebro em pacientes com polineuropatia diabética são significativamente mais elevados do que controles saudáveis (p=0,000). Hiperexpresssão do fator neurotrófico derivado do cérebro no soro foi associada à forma dolorosa da polineuropatia diabética (R=0,392, p=0,012) e obesidade (R=0,412, p=0,001). Por outro lado, alta concentração sérica de receptor da tropomiosina quinase B, associada à polineuropatia diabética indolor por PainDETECT (R=-0,354, p=0,015), baixo peso corporal (R=-0,354, p=0,015) e grave desmielização de fibras nervosas (R=-0,574, p=0,001), indicaram receptor "não funcionante" detectado no soro. Conclusão: A sinalização do receptor da tropomiosina quinase B está envolvida na modulação da dor neuropática e obesidade na polineuropatia diabética.

Neurectomy of C2 for the Treatment of Occipital Neuralgia: Case Report

Occipital neuralgia (ON) is an uncommon cause of headache, and it is characterized by a stabbing paroxysmal pain that radiates to the occipital region. The present study includes a review of the literature and a case report. The etiology of this pathology can vary from traumas, infections, compressions of nerves or vertebrae, skull base surgeries, to degenerative changes and congenital anomalies. However, most of the time, the etiology is considered idiopathic. The diagnosis is essentially clinical. However, it is crucial that other types of primary headache are excluded. The treatment for ON may be based on nerve blocks, medications or surgeries. Neurectomy of the second spinal nerve is among the surgical techniques available.

Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury

The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P<0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP.

Calcitonin as an analgesic agent: review of mechanisms of action and clinical applications / Calcitonina como agente analgésico: revisão dos mecanismos de ação e das aplicações clínicas

Abstract Background and objectives: Calcitonin is a polypeptide hormone regulating the metabolism of calcium in the body. For many years calcitonin has been used to maintain and improve bone mineral density and to reduce the fracture rate. Many studies showed that calcitonin had analgesic role in several painful circumstances. This pain-ameliorating effect is irrelevant to its osteoclastic inhibitory effect and mechanisms like altering Na+ channel and serotonin receptor expression or hypothesis including the endorphin-mediated mechanism were used to explain this effect. In this study we performed a thorough review on the role of calcitonin as an analgesic agent in different scenarios and investigated the fact that calcitonin can be a feasible medication to relieve pain. Method: Many studies focused on the analgesic effect of calcitonin in several painful circumstances, including acute pains related to vertebral fractures, metastasis, migraine and reflex sympathetic dystrophy as well as neuropathic pains related to spinal injuries or diabetes, and phantom pain. Also, calcitonin was showed to be a useful additive to local anesthesia in the case of controlling postoperative pain or trigeminal neuralgia more effectively. However we faced some contradictory data for conditions like lumbar canal stenosis, complex regional pain syndrome, phantom pain and malignancies. Conclusion: This study showed that calcitonin could be helpful analgesic agent in different painful situations. Calcitonin can be considered an eligible treatment for acute pains related to vertebral fractures and a feasible alternative for the treatment of the acute and chronic neuropathic pains where other medications might fail.

Resumo Justificativa e objetivos: A calcitonina é um hormônio polipeptídico que regula o metabolismo do cálcio no organismo. Por muitos anos a calcitonina tem sido usada para manter e melhorar a densidade mineral óssea e reduzir a incidência de fraturas. Muitos estudos mostraram que a calcitonina teve efeito analgésico em várias condições físicas de dor. Esse efeito de melhoria da dor é irrelevante diante de seu efeito inibidor osteoclástico e de mecanismos, tais como a alteração do canal de Na+ e da expressão do receptor de serotonina, inclusive a hipótese do mecanismo mediado pela endorfina, que foram usados para explicar esse efeito. Neste estudo, fizemos uma revisão completa sobre o papel da calcitonina como agente analgésico em diferentes cenários e investigamos o fato de que a calcitonina pode ser uma medicação viável para aliviar a dor. Método: Muitos estudos centraram no efeito analgésico da calcitonina em várias condições de dor, inclusive dores agudas relacionadas a fraturas vertebrais, metástases, enxaqueca e distrofia simpática reflexa, bem como dores neuropáticas relacionadas a lesões medulares ou ao diabetes e dor fantasma. Além disso, a calcitonina mostrou ser um aditivo útil à anestesia local para o controle mais efecaz da dor pós-operatória ou neuralgia do trigêmeo. Porém, nos deparamos com alguns dados contraditórios em condições como estenose do canal lombar, síndrome complexa da dor regional, dor fantasma e malignidades. Conclusão: Este estudo mostrou que a calcitonina pode ser um analgésico útil em diferentes condições de dor. A calcitonina pode ser considerada um tratamento elegível para as dores agudas relacionadas a fraturas vertebrais e uma opção viável para o tratamento das dores neuropáticas agudas e crônicas em que outros medicamentos podem falhar.

Síntomas subagudos y crónicos de la fiebre de chikungunya en un grupo de personas adultas en Ibagué, Colombia / Subacute and chronic symptoms of chikungunya fever in a group of adults in Colombia

Resumen Introducción. La fiebre de chikungunya en Colombia ocasiona una alerta en salud pública que se extiende en el tiempo, dadas las características subagudas y crónicas de la enfermedad. Objetivo. Describir los síntomas subagudos y crónicos en personas mayores de 18 años con fiebre de chikungunya en Ibagué, Colombia. Materiales y métodos. Se hizo un estudio descriptivo con muestreo en bola de nieve de 368 adultos de todas las comunas de Ibagué que presentaban síntomas de la fiebre de chikungunya de más de 12 días de duración. Resultados. Las articulaciones que presentaban dolor en la fase subaguda y crónica de la enfermedad fueron las de manos (84,2 %), rodillas (72,8 %) y tobillos (69,3 %); además de las articulaciones, la planta de los pies fue el sitio en que más frecuentemente se presentó dolor (48,8 %). El dolor articular en manos (p=0,017) y tobillos (p=0,001) y el dolor en la planta de los pies (p=0,002) fueron significativos en las mujeres. La fatiga o el cansancio generalizado se presentaron en el 58,9 % de las personas y se prolongó por más de un año en el 2,4 % de ellas. Conclusiones. Los síntomas de la fase subaguda y crónica de la fiebre de chikungunya coincidieron con los descritos en la literatura médica, su duración se extendió hasta por un año o más en algunos de los casos y su intensidad disminuyó con el tiempo. Los síntomas referidos fueron más comunes en las mujeres que en los hombres.

Abstract Introduction: In Colombia, chikungunya fever creates a warning in public health that extends over time given the subacute and chronic characteristics of the disease. Objective: To describe subacute and chronic symptoms in adult people who suffered chikungunya fever in the city of Ibagué, Colombia. Materials and methods: We conducted a descriptive study with snowball sampling in 368 adults from all the communes of Ibagué, Colombia, who had symptoms of chikungunya fever spanning for more than 12 days. Results: The joints that showed the greatest pain in the subacute and chronic phase of the disease were the hands with 84.2%, knees with 72.8%, and ankles with 69.3%. The soles of the feet were the non-articular areas with greater frequency of pain (48.8%). Joint pain in the hands (p=0.017) and ankles (p=0.001) and pain in the soles of the feet (p=0.002) were significant in women. General fatigue occurred in 58.9% of the subjects and in 2.4% of the population, it lasted for more than a year. Conclusions: The symptoms of the subacute and chronic phase of chikungunya fever were the same reported in the literature, they lasted up to a year or more, and decreased in intensity over time. The referred symptoms were more common in women than in men.

NF-kB mediated CX3CL1 activation in the dorsal root ganglion contributes to the maintenance of neuropathic pain induced in adult male Sprague Dawley rats

Abstract Purpose: To evaluate the role of CX3CL1 and NF-κB in the lumbar disc herniation induced neuropathic pain. Methods: After LDH induced by implantation of autologous nucleus pulposus (NP) on the left L5 nerve root was established, mechanical thresholds and thermal hyperalgesia were tested at relevant time points during an observation period of 28 days. Expression of CX3CL1 and NF-κBin the dorsal root ganglion (DRG) were performed by using Western blotting and RT-PCR. Results: Implantation of autologous nucleus pulposus (NP) induced neuropathic pain, associated with increased mRNA and protein expression of CX3CL1 in the DRG. Moreover, intrathecal injection of neutralizing antibody against CX3CL1 could attenuates LDH-induced persistent pain hypersensitivity. Interestingly, NF-κB activation in the DRGs were found in LDH-induced neuropathic pain. Furthermore, NF-κB downregulation by p65 inhibitor PDTC markedly alleviated LDH-induced mechanical allodynia and thermal hyperalgesia in rat. Importantly, CX3CL1 neutralizing antibody (10 μg/10 μl, i.t.) reduces p-p65 protein level in DRG Conclusions: CX3XL1 could regulate LDH-induced neuropathic pain through NF-κB pathway. Targeting CX3CL1 and NF-κB may represent a potential treatment for neuropathic pain caused by LDH.

Neuropathic pain in leprosy: symptom profile characterization and comparison with neuropathic pain of other etiologies

Introduction: Previous studies reported a high prevalence of neuropathic pain in leprosy, being especially present in "pharmacologically cured" patients. The presence of neuropathic pain in leprosy poses a supplementary burden in patient's quality of life, daily activities, and mood.Objectives: The aim of this study was to assess whether neuropathic pain in leprosy has similar symptom profile as neuropathic pain of other etiologies and to retrospectively assess the efficacy of neuropathic pain medications regularly prescribed to leprosy. Methods: Leprosy and nonleprosy patients had their neuropathic pain characterized by the neuropathic pain symptom inventory (NPSI, ranges from 0 to 100, with 100 being the maximal neuropathic pain intensity) in a first visit. In a second visit, leprosy patients who had significant pain and received pharmacological treatment in the first evaluation were reassessed (NPSI) and had their pain profile and treatment response further characterized, including information on drugs prescribed for neuropathic pain and their respective pain relief. Results: The pain characteristics based on NPSI did not significantly differ between leprosy and nonleprosy neuropathic pain patients in visit 1 after correction for multiple analyses, and cluster analyses confirmed these findings (ie, no discrimination between leprosy and nonleprosy groups; Pearson x2 5 0.072, P 5 0.788). The assessment of pain relief response and the drugs taken by each patient, linear regression analysis showed that amitriptyline, when effective, had the highest percentage of analgesic relief. Conclusions: Neuropathic pain in leprosy is as heterogeneous as neuropathic pain of other etiologies, further supporting the concept that neuropathic pain is a transetiological entity. Neuropathic pain in leprosy may respond to drugs usually used to control pain of neuropathic profile in general, and amitriptiline may constitute a potential candidate drug for future formal clinical trials aimed at controlling neuropathic pain in leprosy.

Herpes zoster en adultos mayores en un hospital privado de la ciudad de Buenos Aires, junio 2013 - mayo 2014 / Herpes zoster in elderly adults in a community hospital in Buenos Aires. June 2013-May 2014

El herpes zoster (HZ) se produce por reactivación del virus varicela zoster. Sus principales factores de riesgo son edad avanzada y presencia de comorbilidades (diabetes, inmunodepresión). Existen escasos datos de HZ en Sudamérica, y especialmente en adultos mayores. Analizamos retrospectivamente las características epidemiológicas y clínicas de 340 pacientes mayores de 60 años atendidos por HZ, entre junio 2013 y mayo 2014. La edad promedio de consulta fue de 74 años (60-100), localización torácica 210 (62%); el 75% (255) de las consultas iniciales se realizaron en guardias. El 68%, 143, presentaron dolor y vesículas, y 4% (14) solo dolor al inicio; el dolor persistió luego de finalizar el episodio en el 41% (139) de los pacientes. El diagnóstico se realizó entre 1 y 3 días de iniciado el cuadro en el 53% (180). El promedio de consultas por episodio fue de 3.6 (1-24). Tratamiento antiviral se indicó en 91% (309) de los pacientes [en 49% (167) fue inadecuado en tiempo o dosis], y tratamiento para el dolor en el 66% (224) de los casos: drogas más usadas (solas o en combinación) AINES (43%, 146), pregabalina (30%, 102), opiáceos (24%, 82), y corticoides (12%, 41). Solo el 9% (31) presentó comorbilidades y el 27% (126) dolor post episodio (duración promedio: 138.7 días). El diagnóstico fue tardío, dificultando el uso correcto de antivirales. El dolor post episodio fue más frecuente que en la literatura consultada; sin embargo, son pocos los datos en este grupo etario.

Herpes zoster (HZ) is caused by reactivation of the varicella zoster virus. Its main risk factor is increasing age and comorbidities. There are limited data on the characteristics of HZ in South America, especially in the elderly. We analyzed epidemiological and clinical characteristics of 340 patients over 60 years assisted for HZ, between June 2013 and May 2014. The average age was 74 years (60-100), 62% (210) had thoracic location; 75% (255) of the initial consultations were held in guards; 68% (143) had pain and vesicles, and 4% (14) only pain at baseline. Pain persisted after finishing the episode in 41% (139). The diagnosis was made between 1 and 3 days from the beginning of the episode in 53% (180 patients). Average number of visits per episode was 3.6 (1-24). Antiviral treatment was supplied to 91% (309); however it was inadequate in dose or time in 49.1% (167 cases). Pain treatment was indicated in 66% (224). Most frequently used drugs (alone or in combination) were non-steroidal painkillers (43%, 146), pregabalin (30%, 102), opiates (24%, 82), and steroids (12%, 41); 9% (31) presented comorbidities; 27% (126) experienced pain after the ending of the episode, with an average duration of 138.7 days. In general, diagnosis was done late, making it difficult to use antivirals correctly. The presence of pain was more frequent than reported in other publications, however there are few data in this age group.

Exogenous neuregulin-1 attenuates STZ-induced diabetic peripheral neuropathic pain in rats

Abstract Purpose: To investigate whether modulating NRG1 could attenuate diabetic neuropathic pain and analyze the underlying mechanism. Methods: Male SD rats were randomly divided into control group, diabetic group, NRG1 intervention group. After STZ-induced 2 weeks, NRG1 intervention daily for consecutive 7 days. 4 weeks after NRG1 intervention, both the mechanical withdrawal threshold and the morphological changes of the dorsal root ganglion and sural nerve were observed. Meanwhile, the expression of NGF, IL-1β, TNF-α in spinal cord were determined. Results: Compared with the diabetic group, NRG1 treatment improved the mechanical withdrawal threshold in diabetic rats, pathological changes of dorsal root ganglion and sural nerve were alleviated by NRG1 treatment with electron microscopy imagine. Moreover, compared with the control group, the expression of NGF was significantly decreased and the production of IL-1β, TNF-α were markedly induced in diabetic group. Furthermore, NRG1 treatment could normalized the above effect as compared to diabetic group. Conclusion: NRG1 exerted positive effects on the behavioral and pathological changes of rats with STZ-induced diabetic neuropathic pain, the underlying mechanism might be related to the promotion of NGF excretion and the inhibition of inflammatory cytokines excretion.

N-acetylcysteine downregulates phosphorylated p-38 expression but does not reverse the increased superoxide anion levels in the spinal cord of rats with neuropathic pain

We determined the effect of N-acetylcysteine (NAC) on the expression of the phosphorylated p38 (p-p38) protein and superoxide anion generation (SAG), two important players in the processing of neuropathic pain, in the lumbosacral spinal cord of rats with chronic constriction injury (CCI)-induced neuropathic pain. The sciatic functional index (SFI) was also measured to assess the functional recovery post-nerve lesion. Thirty-six male Wistar rats were divided equally into the following groups: Naive (rats did not undergo surgical manipulation); Sham (rats in which all surgical procedures involved in CCI were used except the ligature), and CCI (rats in which four ligatures were tied loosely around the right common sciatic nerve), which received 2, 4, or 8 intraperitoneal injections of NAC (150 mg·kg-1·day-1) or saline beginning 4 h after CCI. Rats were sacrificed 1, 3, and 7 days after CCI. The SFI was measured on these days and the lumbosacral spinal cord was used for analysis of p-p38 expression and SAG. CCI induced a decrease in SFI as well as an increase in p-p38 expression and SAG in the spinal cord. The SFI showed a partial recovery at day 7 in saline-treated CCI rats, but recovery was improved in NAC-treated CCI rats. NAC induced a downregulation in p-p38 expression at all time-points evaluated, but did not reverse the increased SAG induced by CCI. Since p-p38 is a mediator in neuropathic pain and/or nerve regeneration, modulation of this protein may play a role in NAC-induced effects in CCI rats.

High prevalence of neuropathic pain in the hand of patients with traumatic brachial plexus injury: a cross-sectional study / Alta prevalência de dor neuropática em sujeitos com lesão traumática do plexo braquial: um estudo de corte transversal

ABSTRACT Objective To describe the pain profile of patients with traumatic brachial plexus injury. Methods We enrolled 65 patients with traumatic brachial plexus injury. The Douleur Neuropathique 4 questionnaire was used to classify pain and the SF-36 was used to evaluate quality of life. Results The patients with traumatic brachial plexus injury were predominantly young male victims of motorcycle accidents. Pain was present in 75.4% of the individuals and 79% presented with neuropathic pain, mostly located in the hands (30.41%). The use of auxiliary devices (p = 0.05) and marital status (p = 0.03) were both independent predictors of pain. Pain also impacted negatively on the quality of life (p = 0.001). Conclusions Pain is frequent in patients with traumatic brachial plexus injury. Despite the peripheral nervous system injury, nociceptive pain is not unusual. Pain evaluation, including validated instruments, is essential to guide optimal clinical management of patients with the condition.

RESUMO Objetivo Descrever o perfil de dor de sujeitos com lesão traumática do plexo braquial. Métodos Nós incluímos 65 indivíduos com lesão traumática do plexo braquial. O Douleur Neuropathique 4 foi usado para classificar a dor e o SF-36 foi usado para avaliar a qualidade de vida. Resultados Sujeitos com lesão traumática do plexo braquial eram em sua maioria homens jovens, vítimas de acidentes motociclísticos. A dor esteve presete em 75.4% dos indivíduos e 79% deles apresentaram dor neuropática, mais frequentemente localizada nas mãos (30.41%). O uso de dispositivos auxiliares (p = 0.05) e o estado civil foram, ambos, preditores independentes de dor. A dor ainda impactou negativamente da qualidade de vida (p = 0.001). Conclusões A dor é frequente em sujeitos com lesão traumática do plexo braquial. Apesar de envolver uma lesão do sistema nervoso a dor nociceptiva não é infrequente. A avaliação da dor, incluindo instrumentos validados, é essencial para direcionar as condutas clínicas de sujeitos com esta condição.

Paravertebral block for management of acute postoperative pain and intercostobrachial neuralgia in major breast surgery / Bloqueio paravertebral no controle da dor aguda pós-operatória e dor neuropática do nervo intercostobraquial em cirurgia mamária de grande porte

Abstract Background: Several locoregional techniques have been described for the management of acute and chronic pain after breast surgery. The optimal technique should be easy to perform, reproducible, with little discomfort to the patient, little complications, allowing good control of acute pain and a decreased incidence of chronic pain, namely intercostobrachial neuralgia for being the most frequent entity. Objectives: The aim of this study was to evaluate the paravertebral block with preoperative single needle prick for major breast surgery and assess initially the control of postoperative nausea and vomiting (PONV) and acute pain in the first 24 h and secondly the incidence of neuropathic pain in the intercostobrachial nerve region six months after surgery. Methods: The study included 80 female patients, ASA I-II, aged 18-70 years, undergoing major breast surgery, under general anesthesia, stratified into 2 groups: general anesthesia (inhalation anesthesia with opioids, according to hemodynamic response) and paravertebral (paravertebral block with single needle prick in T4 with 0.5% ropivacaine + adrenaline 3 µg mL−1 with a volume of 0.3 mL kg−1 preoperatively and subsequent induction and maintenance with general inhalational anesthesia). In the early postoperative period, patient-controlled analgesia (PCA) was placed with morphine set for bolus on demand for 24 h. Intraoperative fentanyl, postoperative morphine consumption, technique-related complications, pain at rest and during movement were recorded at 0 h, 1 h, 6 h and 24 h, as well as episodes of PONV. All variables identified as factors contributing to pain chronicity age, type of surgery, anxiety according to the Hospital Anxiety and Depression Scale (HADS), preoperative pain, monitoring at home; body mass index (BMI) and adjuvant chemotherapy/radiation therapy were analyzed, checking the homogeneity of the samples. Six months after surgery, the incidence of neuropathic pain in the intercostobrachial nerve was assessed using the DN4 scale. Results: The Visual Analog Scale (VAS) values of paravertebral group at rest were lower throughout the 24 h of study 0 h 1.90 (±2.59) versus 0.88 (±1.5) 1 h 2.23 (±2.2) versus 1.53 (±1.8) 6 h 1.15 (±1.3) versus 0.35 (±0.8); 24 h 0.55 (±0.9) versus 0.25 (±0.8) with statistical significance at 0 h and 6 h. Regarding movement, paravertebral group had VAS values lower and statistically significant in all four time points: 0 h 2.95 (±3.1) versus 1.55 (±2.1); 1 h 3.90 (±2.7) versus 2.43 (±1.9) 6 h 2.75 (±2.2) versus 1.68 (±1.5); 24 h 2.43 (±2.4) versus 1.00 (±1.4). The paravertebral group consumed less postoperative fentanyl (2.38 ± 0.81 µg kg−1 versus 3.51 ± 0.81 µg kg−1) and morphine (3.5 mg ± 3.4 versus 7 mg ± 6.4) with statistically significant difference. Chronic pain evaluation of at 6 months of paravertebral group found fewer cases of neuropathic pain in the intercostobrachial nerve region (3 cases versus 7 cases), although not statistically significant. Conclusions: Single-injection paravertebral block allows proper control of acute pain with less intraoperative and postoperative consumption of opioids but apparently it cannot prevent pain chronicity. Further studies are needed to clarify the role of paravertebral block in pain chronicity in major breast surgery.

Resumo Justificativa: Estão descritas várias técnicas locorregionais para a abordagem da dor aguda e dor crônica após cirurgia de mama. O ideal seria uma técnica fácil de fazer, reprodutível, com pouco desconforto para as doentes, com poucas complicações e que permitirá um bom controle da dor aguda e uma diminuição da incidência de dor crônica, notadamente dor neuropática do intercostobraquial, por ser a entidade mais frequente. Objetivos: Estudar a aplicação de bloqueio paravertebral com picada única no pré-operatório de cirurgia mamária de grande porte. Avaliar numa primeira fase o controle de dor aguda e náuseas-vômitos no pós-operatório (NVPO) nas primeiras 24 horas e numa segunda fase a incidência de dor neuropática na região do nervo intercostobraquial seis meses após a cirurgia. Métodos: Foram incluídas 80 doentes do sexo feminino, ASA I-II, entre 18 e 70 anos, submetidas a cirurgia mamária de grande porte sob anestesia geral, estratificadas em dois grupos: anestesia geral (anestesia geral inalatória com opioides segundo resposta hemodinâmica) e paravertebral (bloqueio paravertebral com picada única em T4 com ropivacaína 0,5% + adrenalina 3 µg/mL com um volume de 0,3 mL/kg pré-operatoriamente e posterior indução e manutenção com anestesia geral inalatória). No pós-operatório imediato foi colocada PCA (Patient-controlled analgesia) de morfina programada com bolus a demanda durante 24 horas. Foram registados fentanil intraoperatório, consumo de morfina pós-operatória, complicações relacionadas com as técnicas, dor em repouso e ao movimento a 0, 1 h, 6 h e 24 h, assim como os episódios de NVPO. Foram analisadas todas as variáveis identificadas como fatores de cronificação da dor idade, tipo de cirurgia, ansiedade segundo escala de HADS (Hospital Anxiety and Depression scale), dor pré-operatória; acompanhamento no domicílio; índice de massa corporal (IMC), tratamentos adjuvantes de quimioterapia/radioterapia e foi verificada a homogeneidade das amostras. Aos seis meses da cirurgia foi avaliada, segundo escala DN4, a incidência de dor neuropática na área do nervo intercostobraquial. Resultados: O grupo paravertebral teve valores de VAS (Escala Visual Analógica) em repouso mais baixos ao longo das 24 horas de estudo 0 h 1,90 (± 2,59) versus 0,88 (± 1,5); 1 h 2,23 (± 2,2) versus 1,53 (± 1,8); 6 h 1,15 (± 1,3) versus 0,35 (± 0,8); 24 h 0,55 (± 0,9) versus 0,25 (± 0,8) com significado estatístico às 0 e às 6 horas. Em relação ao movimento o grupo paravertebral teve valores de VAS mais baixos e com significância estatística nos quatro momentos de avaliação: 0 h 2,95 (± 3,1) versus 1,55 (± 2,1); 1 h 3,90 (± 2,7) versus 2,43 (± 1,9) 6 h 2,75 (± 2,2) versus 1,68 (± 1,5); 24 h 2,43 (± 2,4) versus 1,00 (± 1,4). O grupo paravertebral consumiu menos fentanil (2,38 ± 0,81 µg/Kg versus 3,51 ± 0,81 µg/Kg) e menos morfina no pós-operatório (3,5 mg ± 3,4 versus 7 mg ± 6,4), com diferença estatisticamente significativa. Na avaliação de dor crônica aos seis meses no grupo paravertebral houve menos casos de dor neuropática na região do nervo intercostobraquial (três versus sete) embora sem significância estatística. Conclusões: O bloqueio paravertebral com picada única permite um adequado controle da dor aguda com menor consumo de opioides intraopreatórios e pós-operatórios, mas aparentemente não consegue evitar a cronificação da dor. Mais estudos são necessários para esclarecer o papel do bloqueio paravertebral na cronificação da dor em cirurgia mamária de grande porte.

Translation and transcultural adaptation of Pain Quality Assessment Scale (PQAS) to brazilian version / Tradução e adaptação transcultural da Pain Quality Assessment Scale (PQAS) para a versão brasileira

INTRODUCTION: Most cancer patients are treated with chemotherapy, and peripheral neuropathy is a serious and common clinical problem affecting patients undergoing cancer treatment. However, the symptoms are subjective and underdiagnosed by health professionals. Thus, it becomes necessary to develop self-report instruments to overcome this limitation and improve the patient's perception about his medical condition or treatment. OBJECTIVE: Translate and culturally adapt the Brazilian version of the Pain Quality Assessment Scale, constituting a useful tool for assessing the quality of neuropathic pain in cancer patients. METHOD: The procedure followed the steps of translation, back translation, analysis of Portuguese and English versions by a committee of judges, and pretest. Pretest was conducted with 30 cancer patients undergoing chemotherapy following internationally recommended standards, and the final versions were compared and evaluated by a committee of researchers from Brazil and MAPI Research Trust, the scale's creators. RESULTS: Versions one and two showed 100% semantic equivalence with the original version. Back-translation showed difference between the linguistic translation and the original version. After evaluation by the committee of judges, a flaw was found in the empirical equivalence and idiomatic equivalence. In pretest, two people did not understand the item 12 of the scale, without interfering in the final elaboration. CONCLUSION: The translated and culturally adapted instrument is now presented in this publication, and currently it is in the process of clinical validation in Brazil.

INTRODUÇÃO: a maioria dos pacientes com câncer são tratados com quimioterápicos e a neuropatia periférica é um problema clínico sério e comum que afeta os pacientes em tratamento oncológico. Entretanto, tais sintomas são subjetivos sendo subdiagnosticado pelos profissionais de saúde. Assim, torna-se necessário o desenvolvimento de instrumentos de autorrelato para superar essa limitação e melhorar a percepção do paciente sobre o seu tratamento ou condição clínica. OBJETIVO: traduzir e adaptar transculturalmente a versão brasileira do Pain Quality Assessment Scale (PQAS), constituindo em um instrumento útil de avaliação da qualidade da dor neuropática em pacientes com câncer. MÉTODO: o procedimento seguiu as etapas de tradução, retrotradução, análise das versões português e inglês por um comitê de juízes e pré-teste. O pré-teste foi realizado em 30 pacientes com câncer em tratamento quimioterápico seguindo normas internacionalmente recomendadas, sendo as versões finais comparadas e avaliadas por comitê de pesquisadores brasileiros e da MAPI Research Trust, originadores da escala. RESULTADOS: as versões um e dois apresentaram 100% de equivalência semântica com a versão original. Na retrotradução houve diferenças na tradução linguística com a versão original. Após a avaliação do Comitê de Juízes, foi encontrada uma falha na equivalência empírica e na equivalência idiomática. No pré-teste, duas pessoas não entenderam o item 12 da escala, sem interferir na elaboração final da mesma. CONCLUSÃO: o instrumento agora traduzido e adaptado transculturalmente é apresentado nessa publicação e, atualmente, encontra-se em processo de validação clínica no Brasil.

Clinical and neurophysiological features of the hereditary neuropathy with liability to pressure palsy due to the 17p11. 2 deletion / Aspectos clínicos e neurofisiológicos de pacientes com a neuropatia hereditária com a susceptibilidade à pressão associada à deleção 17p11. 2

ABSTRACT The hereditary neuropathy with liability to pressure palsies (HNPP) is an autossomal dominant disorder manifesting recurrent mononeuropathies. Objective Evaluate its clinical and nerve conduction studies (NCS) characteristics, searching for diagnostic particularities. Method We reviewed the neurological manifestations of 39 and the NCS of 33 patients. Results Family history was absent in 16/39 (41%). The onset complaints were weakness in 24, pain in 6, sensory deficit in 5 and paresthesias in 4. Pain was seen in 3 other patients. The following neuropathy patterns were found: multiple mononeuropathy (26), mononeuropathy (7), chronic sensorimotor polyneuropathy (4), chronic sensory polyneuropathy (1) and unilateral brachial plexopathy (1). NCS showed a sensorimotor neuropathy with focal conduction slowing in 31, two had mononeuropathy and another brachial plexopathy. Conclusion HNPP presentation is variable and may include pain. The most frequent pattern is of an asymmetrical sensory and motor neuropathy with focal slowing at specific topographies on NCS.

RESUMO A neuropatia hereditária com susceptibilidade à pressão (HNPP) é uma doença autossômica dominante que manifesta mononeuropatias recorrentes. Objetivo Avaliar as características clínicas e os estudos da condução nervosa (ECN) procurando particularidades diagnósticas. Método Revisamos as características clínicas de 39 e os ECN de 33 pacientes. Resultados História familiar ausente em 16/39 (41%). As manifestações iniciais foram: fraqueza em 24, dor em 6, déficit sensitivo em 5 e parestesias em 4. Dor foi referida por outros 3 pacientes. Os seguintes padrões de neuropatia foram observados: mononeuropatia múltipla (26), mononeuropatia (6), polineuropatia sensitivo-motora (4), polineuropatia sensitiva (1) e plexopatia braquial unilateral (1). Os ECN mostraram uma neuropatia sensitivo-motora com redução focal da velocidade de condução em 31, dois tinham mononeuropatia e outro plexopatia braquial. Conclusão A apresentação da HNPP é variável e pode incluir dor. O padrão mais frequente é o de uma neuropatia sensitivo-motora assimétrica com alentecimentos focais da condução em topografias específicas nos ECN.

Dor neuropática em pacientes com HIV/AIDS em uso de terapia antirretroviral / Neuropathic pain in HIV/AIDS patients using antiretroviral therapy

A infecção pelo vírus da imunodeficiência humana (HIV) representa um dos maiores problemas de saúde da atualidade em virtude de seu caráter pandêmico e gravidade. O uso da terapia antirretroviral está associado ao desenvolvimento de diferentes tipos de dor, sendo a dor neuropática uma delas. A dor neuropática ocorre pela lesão do sistema nociceptivo, que envolve mudanças moleculares, fisiológicas e anatômicas. Considerando que a infecção por HIV gera custos elevados para o sistema de saúde, e que suas comorbidades elevam ainda mais esses custos, a compreensão dos mecanismos da dor nessa população possibilita uma melhor assistência e uma redução da carga para o sistema. A dor neuropática pode apresentar diferentes possíveis mecanismos fisiopatológicos envolvidos, tornando-se um desafio para o tratamento de pacientes com HIV. A compreensão sobre a neurofisiologia da dor neuropática e o HIV pode promover melhores abordagens aos pacientes e a redução de comorbidades associadas, com impacto na qualidade de vida (AU)

Human immunodeficiency virus (HIV) infection is a major health problem nowadays due to its pandemic character and severity. The use of antiretroviral therapy is associated with the development of different types of pain, and neuropathic pain is one of them. Neuropathic pain is caused by an injury to the nociceptive system, which involves molecular, physiological and anatomical changes. Considering that HIV infection generates high costs for the health system, and that its comorbidities raise such costs even more, understanding the mechanisms of pain in this population can result in better care practices and reduction of burden to the system. Neuropathic pain may present different pathophysiological mechanisms becoming a challenge for HIV treatment. The understanding of the neurophysiology of neuropathic pain and the HIV can promote better patient approaches and the reduction of associated comorbidities with an impact on quality of life (AU)

Neuropathic pain in leprosy

Nerve impairment is a key clinical aspect of leprosy and may present the distribution of mononeuropathy or multiple nerve trunks, small cutaneous nerve fibers, and free nerve endings. The clinical range of leprosy is determined by individual cell-mediated immune response to infection that also may play a role in different types of pain syndromes in leprosy. Previous studies reported a high prevalence of neuropathic pain in leprosy. In an Ethiopian study with 48 patients, pure nociceptive pain was experienced by 43% of patients and pure neuropathic pain (NeP) by 11% of patients. In an Indian study, 21.8% of leprosy patients had pain with neuropathic characteristics. These rates underlie the need to develop tools for the early diagnosis and detection of infection and its complications, such as nerve damage and pain. In a larger sample with leprosy-associated NeP (n = 90), we have applied the Douleur Neuropathique en 4 questions (DN4) and found sensitivity = 97.1% and specificity = 57.9%. The high sensitivity of this tool in leprosy patients suggests that it could be a valuable tool to screen for neuropathic pain in this population and could be used as part of health care programs aimed at detecting, treating, and rehabilitating leprosy in endemic areas.