Redefiniendo dolor agudo postoperatorio: dolor incisional / Redefining acute postoperative pain: incisional pain

El adecuado manejo perioperatorio del dolor agudo y la elección de la técnica anestésica influyen en la incidencia de complicaciones a corto, mediano y largo plazo, encontrándose en este grupo el desarrollo de dolor crónico no oncológico (DCNO). Debido al aumento de la prevalencia de dolor crónico no oncológico y su relación con un manejo inadecuado o insuficiente del dolor agudo en el periodo perioperatorio, hemos realizado una revisión de su fisiopatología, los factores de riesgo y las técnicas preventivas que permitirían mitigar y/o disminuir su incidencia.

The adequate perioperative management of acute pain and the correct choice of the anesthetic technique influence the incidence of complications in the short, medium and long term, being in this group the development of chronic non-oncological pain (CNOP). Due to the increase in the prevalence of non-oncological chronic pain and its relation with an inadequate or insufficient management of acute pain in the perioperative period, we have carried out a review of its pathophysiology, risk factors and preventive techniques that would allow mitigating and/ordecrease its incidence.

Secondary hyperalgesia occurs regardless of unilateral or bilateral knee osteoarthritis involvement in individuals with mild or moderate level / A hiperalgesia secundária ocorre independentemente do envolvimento unilateral ou bilateral da osteoartrite de joelho em indivíduos com doença leve ou moderada

ABSTRACT Background: Secondary hyperalgesia in individuals with less severe levels of knee osteoarthritis remains unclear. The objective of this study was to measure the pressure pain threshold of individuals with mild or moderate knee osteoarthritis and compare with no osteoarthritis. Methods: Ten healthy controls and 30 individuals with mild or moderate knee osteoarthritis divided into two groups (unilateral and bilateral involvement) were included. Dermatomes in lumbar levels (L1, L2, L3, L4 and L5) and sacral level (S1 and S2), myotomes (vastus medialis, vastus lateralis, rectus femoris, adductor longus, tibialis anterior, peroneus longus, iliacus, quadratus lumborum, and popliteus muscles), and sclerotomes in lumbar levels (L1-L2, L2-L3, L3-L4, L4-L5 supraspinous ligaments), over the L5-S1 and S1-S2 sacral areas, pes anserinus bursae, and at the patellar tendon pressure pain threshold were assessed and compared between individuals with and without knee osteoarthritis. Results: Knee osteoarthritis groups (unilateral and bilateral) reported lower pressure pain threshold compared to the control group in most areas (dermatomes, myotomes, and sclerotomes). There were no between group differences in the supra-spinous ligaments and over the L5-S1 and S1-S2 sacral areas of the sclerotomes. No difference was seen between knee osteoarthritis. Conclusion: These findings suggest that individuals with mild to moderate knee osteoarthritis had primary and secondary hyperalgesia, independent of unilateral or bilateral involvement. These results suggest that the pain have to be an assertive focus in the clinical practice, independent of the level of severity or involvement of knee osteoarthritis.

RESUMO Introdução: A ocorrência de hiperalgesia secundária em indivíduos com níveis menos graves de osteoartrite de joelho ainda é incerta. O objetivo deste estudo foi medir o limiar de dor à pressão (LDP) de indivíduos com osteoartrite de joelho (OAJ) leve ou moderada e comparar com indivíduos sem osteoartrite. Métodos: Foram incluídos 10 controles saudáveis e 30 indivíduos com OAJ leve ou moderada, divididos em dois grupos (envolvimento unilateral e bilateral). Foi avaliado e comparado o LDP em dermátomos (L1, L2, L3, L4, L5, S1 e S2), miótomos (músculos vasto medial, vasto lateral, reto femoral, adutor longo, tibial anterior, fibular longo, ilíaco, quadrado lombar e poplíteo) e esclerótomos (ligamentos supraespinais L1-L2, L2-L3, L3-L4, L4-L5), sobre as áreas sacrais L5-S1 e S1-S2, bolsa anserina e tendão patelar entre os indivíduos com e sem OAJ. Resultados: Os grupos OAJ (unilateral e bilateral) relataram menor LDP em comparação com o grupo controle na maior parte das áreas (dermátomos, miótomos e esclerótomos). Não houve diferenças entre os grupos nos ligamentos supraespinais e ao longo das áreas sacrais L5-S1 e S1-S2 dos esclerótomos. Não foi observada qualquer diferença entre os indivíduos com OAJ. Conclusão: Esses achados sugerem que os indivíduos com OAJ leve a moderada tinham hiperalgesia primária e secundária, independentemente do acometimento unilateral ou bilateral. Esses resultados sugerem que a dor precisa ser um foco assertivo na prática clínica, independentemente do grau de gravidade ou envolvimento da OAJ.

Osteoarthritis model induced by intra-articular monosodium iodoacetate in rats knee

ABSTRACT PURPOSE: To evaluate the usefulness of a knee osteoarthritis model through functional, radiological and microscopic changes of the synovial membrane. METHODS: Forty eight rats were divided randomly into two groups. The first received 0.9% saline in the joint and corresponded to the control group. The second was submitted to experimental osteoarthritis of the right knee induced by monosodium iodoacetate and corresponded to the osteoarthritis group. All animals were subjected to comparative tests of forced ambulation and joint movements, inability to articulate and tactile allodynia on day 1 post-experiment by forced ambulation (Roto-rod test), joint assessment of disability (weight bearing test) and assessment of tactile allodynia (Von Frey test). After inflammatory induction they were divided into four sub-groups corresponding to the scheduled death in 7, 14, 21 and 28 days when they were submitted to radiographic examination of the knee, arthrotomy and collection of the synovial membrane. RESULTS: The osteoarthritis group showed significant differences compared to control group on days 7 and 14 in Roto-rod, in weight bearing and Von Frey tests in all days, and in radiological evaluation. Microscopic examination of the synovial membrane showed abnormalities of inflammatory character at all stages. CONCLUSION: The osteoarthritis induced by intra-articular monosodium iodoacetate in rats knee is a good model to be used in related research, because it provides mensurable changes on joint movements, tactile allodynia, progressive radiological degeneration and microscopic inflammation of the synovial membrane, that represent markers for osteoarthritis evaluation

Comparative evaluation of somatosensory mechanisms involved in orofacial somatic, visceral and neuropathic pain / Avaliação comparativa dos mecanismos somatossensoriais envolvidos na gênese das dores orofaciais de origem somática, visceral e neuropática

Orofacial pain conditions can be classified into somatic, visceral or neuropathic pain. Somatic pain is triggered by a noxious stimulus generally inducted by peripheral traumas, such as dental implants surgeries (IMP). Visceral pain initiates within internal body tissues and is normally triggered by inflammation, as in inflammatory toothaches (IT). The third condition is neuropathic pain, which results from persistent injury to the peripheral nerve as in Atypical Odontalgia (AO). The aims of this study were: 1- to investigate somatosensory abnormalities, using mechanical, painful, and electrical quantitative sensory testing (QST), in somatic (IMP patients), visceral (IT) and neuropathic pain (AO); 2- to quantify how accurately QST discriminates an IT or AO diagnosis; and 3- to investigate the influence implant surgeries or pulpectomy may have on somatosensory system and sensory nerve fibers. Sixty subjects were divided in three groups: IMP (n = 20), IT (n = 20) and AO group (n = 20). A sequence of five QSTs and the Conditioned Pain Modulation Test (CPM) were performed one month and three months after dental implant surgery (IMP group) or pulpectomy (IT group). AO group was evaluated only at baseline. QST comprehended Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Dynamical Mechanical Allodynia (DMA), Current Perception Threshold (CPT) for A-beta (frequency of 2000Hz), A-delta (250Hz) and C fibers (5Hz) and Temporal Summation Test (TS). "Z" score transformation were applied to the data, and within and between groups were statistically analyzed using two-way ANOVA. In addition, the receiver operating characteristic curve analysis, diagnostic accuracy, sensitivity, specificity, likelihood ratios, and diagnostic odds ratio of QSTs were calculated (α = 5%). The findings of this study proved that: 1- loss of function for touch threshold and electrical threshold of C fibers is present in inflammatory toothache; 2- allodynia, hyperalgesia, gain of function for touch and pain thresholds and impaired pain modulation is detected in atypical odontalgia; 3- some QSTs may be used as complementary tests in the differential diagnosis of atypical odontalgia and inflammatory toothache with strong accuracy; 4- the most accurate QSTs for differential diagnosis between subjects with AO and IT were MDT, MPT and DMA where touch threshold forces > 1 g/mm2 and pain threshold forces > 10g/mm2 can be used to accurately discriminate AO from IT; and 5- no somatosensory modification is found after implant surgery and reduced electrical threshold in C fiber is found for patients with inflammatory toothache after 3 months of pulpectomy.(AU)

As dores orofaciais podem ser classificadas em dores somáticas, viscerais ou neuropáticas. A dor somática está relacionada a um estímulo nocivo evidente, geralmente associada a um trauma periférico, como por exemplo, nas cirurgias de implantes (IMP). As dores viscerais têm origem dentro dos órgãos e cavidades internas do corpo e são ativadas pela inflamação, como no exemplo da dor de dente do tipo Pulpite Aguda (PA). A terceira condição é a dor neuropática, que resulta de uma lesão persistente ao nervo periférico, como ocorre na Odontalgia Atípica (OA). Os objetivos deste estudo foram: 1- avaliar as alterações somatossensoriais, por meio do uso de Testes Sensoriais Quantitativos (TSQ) mecânicos, dolorosos e elétricos em dores somáticas (pacientes IMP), viscerais (PA) e neuropáticas (OA); 2- quantificar a acurácia dos TSQs na descriminação diagnóstica de uma PA ou OA; e 3- investigar alterações somatossensoriais e nas fibras nervosas sensoriais após cirurgia de instalação de implantes dentários ou pulpectomia. Sessenta sujeitos foram divididos em três grupos: IMP (n = 20), PA (n = 20) e OA (n = 20). Uma sequência de cinco TSQs e o teste de Controle da Modulação da Dor (CMD) foram realizados um mês e três meses após cirurgia de implantes (grupo IMP) ou pulpectomia (grupo PA). No grupo OA, os testes foram realizados somente uma vez no início do estudo. Os TSQs englobaram o Limiar de Detecção Mecânica (LDM), Limiar de Dor Mecânica (LDoM), Alodinia Mecânica Dinâmica (AMD), Limiar de Percepção de Corrente (LPC) para fibras A-beta (frequência de 2000Hz), A-delta (250Hz) e C (5 Hz), e o teste de Somação Temporal (ST). A transformação em escores de "Z" foi aplicada aos dados, e diferenças intra e inter-grupos foram analisadas usando ANOVA de medidas repetidas. Ainda, a acurácia diagnóstica dos TSQs foi medida por meio da sensibilidade, especificidade, razão de verossimilhança e razão de chances para diagnóstico (α = 5%). Os resultados deste estudo mostraram que: 1- perda da função em limiar táctil e limiar elétrico de fibras C está presente na Pulpite Aguda; 2- alodinia, hiperalgesia, ganho de função nos limiares de tato e de dor, e modulação da dor prejudicada são encontrados em pacientes com odontalgia atípica; 3- alguns TSQs podem ser usados como testes diagnósticos complementares ao diagnóstico diferencial entre PA e OA; 4- os TSQs com maior acurácia para o diagnóstico diferencial entre indivíduos com PA e OA foram LDM LDoM e AMD, onde uma força maior que 1 g/mm2 para limiar de tato e maior que 10 g/mm2 para limiar de dor podem ser usados com precisão; e 5- nenhuma alteração somatossensorial é encontrada após cirurgia de implantes e uma redução no limiar elétrico em fibras C é encontrado em pacientes com PA após 3 meses da pulpectomia.(AU)

An improved experimental model for peripheral neuropathy in rats

A modification of the Bennett and Xie chronic constriction injury model of peripheral painful neuropathy was developed in rats. Under tribromoethanol anesthesia, a single ligature with 100% cotton glace thread was placed around the right sciatic nerve proximal to its trifurcation. The change in the hind paw reflex threshold after mechanical stimulation observed with this modified model was compared to the change in threshold observed in rats subjected to the Bennett and Xie or the Kim and Chung spinal ligation models. The mechanical threshold was measured with an automated electronic von Frey apparatus 0, 2, 7, and 14 days after surgery, and this threshold was compared to that measured in sham rats. All injury models produced significant hyperalgesia in the operated hind limb. The modified model produced mean ± SD thresholds in g (19.98 ± 3.08, 14.98 ± 1.86, and 13.80 ± 1.00 at 2, 7, and 14 days after surgery, respectively) similar to those obtained with the spinal ligation model (20.03 ± 1.99, 13.46 ± 2.55, and 12.46 ± 2.38 at 2, 7, and 14 days after surgery, respectively), but less variable when compared to the Bennett and Xie model (21.20 ± 8.06, 18.61 ± 7.69, and 18.76 ± 6.46 at 2, 7, and 14 days after surgery, respectively). The modified method required less surgical skill than the spinal nerve ligation model.

Exercise training attenuates acute hyperalgesia in streptozotocin-induced diabetic female rats

OBJECTIVES: We investigated the effects of chronic (eight weeks) low-to moderate-intensity swimming training on thermal pain sensitivity in streptozotocin-induced diabetic female rats. METHODS: Female Wistar rats (n = 51) were divided into the following groups: trained streptozotocin-induced diabetic rats [hyperglycemic trained (HT)], sedentary streptozotocin-induced diabetic rats [hyperglycemic sedentary (HS)], normoglycemic trained rats (NT) and normoglycemic sedentary rats (NS). Diabetes was induced by a single injection of streptozotocin (50 mg/kg, i.p.). One day after the last exercise protocol (60 min/day, five days/week for eight weeks) in the trained groups or after water stress exposure (ten min/twice a week) in the sedentary groups, the rats were subjected to a hot plate test. RESULTS: After eight weeks of swimming training, streptozotocin-induced diabetic rats presented a significantly lower body mass (trained: 219.5±29 g, sedentary: 217.8±23 g) compared with the normoglycemic groups (trained: 271±24 g, sedentary: 275.7±32 g). Interestingly, we did not find differences in blood glucose levels (mg/dl) between the trained and sedentary groups of the hyperglycemic or normoglycemic rats (HT: 360.2±6.6, HS: 391.7±6.7, NT: 83.8±14.0, NS: 77.5±10.1). In the hot plate test, the rats from the HT group presented a significantly lower latency than the other rats (HT: 11.7±7.38 s, HS: 7.02±7.38 s, NT: 21.21±7.64 s, NS: 22.82±7.82 s). CONCLUSION: Low-to-moderate swimming training for a long duration reduces thermal hyperalgesia during a hot plate test in streptozotocin-induced diabetic female rats.

Participation of neuronal nitric oxide synthase in experimental neuropathic pain induced by sciatic nerve transection

Nerve injury leads to a neuropathic pain state that results from central sensitization. This phenomenom is mediated by NMDA receptors and may involve the production of nitric oxide (NO). In this study, we investigated the expression of the neuronal isoform of NO synthase (nNOS) in the spinal cord of 3-month-old male, Wistar rats after sciatic nerve transection (SNT). Our attention was focused on the dorsal part of L3-L5 segments receiving sensory inputs from the sciatic nerve. SNT resulted in the development of neuropathic pain symptoms confirmed by evaluating mechanical hyperalgesia (Randall and Selitto test) and allodynia (von Frey hair test). Control animals did not present any alteration (sham-animals). The selective inhibitor of nNOS, 7-nitroindazole (0.2 and 2 µg in 50 µL), blocked hyperalgesia and allodynia induced by SNT. Immunohistochemical analysis showed that nNOS was increased (48 percent by day 30) in the lumbar spinal cord after SNT. This increase was observed near the central canal (Rexed’s lamina X) and also in lamina I-IV of the dorsal horn. Real-time PCR results indicated an increase of nNOS mRNA detected from 1 to 30 days after SNT, with the highest increase observed 1 day after injury (1469 percent). Immunoblotting confirmed the increase of nNOS in the spinal cord between 1 and 15 days post-lesion (20 percent), reaching the greatest increase (60 percent) 30 days after surgery. The present findings demonstrate an increase of nNOS after peripheral nerve injury that may contribute to the increase of NO production observed after peripheral neuropathy.

Comportamentos espontâneos e induzidos em ratos com dor neuropática por constrição crônica do nervo ciático / Spontaneous and induced behaviors in rats with neuropathic pain by chronic sciatic nerve constriction

JUSTIFICATIVA E OBJETIVOS: A dor neuropática é uma condição frequente e desafiadora no que concerne ao tratamento, necessitando assim do uso de modelos experimentais para a melhor compreensão de seus mecanismos. O objetivo deste estudo foi reproduzir cirurgicamente o modelo de constrição crônica do nervo ciático e quantificar os comportamentos auto-dirigidos sugestivos de dor neuropática crônica experimental durante quatro semanas.MÉTODO: Foram utilizados 21 ratos Wistar divididos em três grupos: normal (n = 7), pseudo-cirúrgico (n = 7) e cirúrgico (n = 7). No grupo pseudo-cirúrgico, procedeu-se apenas a exposição bilateral do nervo ciático, sem lesioná-los. No grupo cirúrgico procedeu-se a exposição do nervo ciático à direita e então constrição com fio mononylon 4.0 em quatro locais, separados por 2 mm de distância. No membro esquerdo, fez-se apenas exposição do nervo ciático, sem lesioná-lo. RESULTADOS: A análise dos comportamentos revelou um aumento significativo (p < 0,05) de coçar-se e morder-se nos membros posteriores direito e esquerdo (em espelho), com predomínio à direita. Além disso, houve diminuição significativa de empinar-se e exploratórios como correr, andar, farejar, e aumento significativo de descansar/dormir e congelar-se. A análise dos testes térmicos revelou presença de alodínia (40º C) e hiperalgesia (46º C) nos membros posteriores direito e esquerdo.CONCLUSÃO: O modelo induziu mononeuropatia ciática dolorosa expressa por comportamentos espontâneos sugestivos de dor crônica, além de alodínia e hiperalgesia.

BACKGROUND AND OBJECTIVES: Neuropathic pain is a frequent and challenging condition in terms of management, thus requiring the use of experimental models to better understand its mechanisms. This study aimed at surgically reproducing chronic sciatic nerve constriction model and at quantifying self-directed behaviors suggestive of experimental chronic neuropathic pain during four weeks.METHOD: Twenty-one Wistar rats were divided in three groups: normal (n = 7), pseudo-surgical (n = 7) and surgical (n = 7). The pseudo-surgical group was submitted to bilateral sciatic nerve exposure without injury. The surgical group was submitted to right sciatic nerve exposure and constriction with mononylon thread 4.0 in four sites 2 mm apart from each other. Left sciatic nerve was exposed without injury. RESULTS: Behavioral analysis has shown significant increase (p < 0.05) in scratching and biting right and left hind limbs (in mirror), predominantly to the right. In addition there has been significant decrease in rearing up and exploratory behaviors such as running, walking and sniffing, and significant increase in resting / sleeping and freezing. Thermal tests analysis has shown allodynia (40º C) and hyperalgesia (46º C) in right and left hind limbs. CONCLUSION: The model has induced painful sciatic single neuropathy expressed by spontaneous behaviors suggestive of chronic pain, in addition to allodynia and hyperalgesia

Streptozotocin-induced mechanical hypernociception is not dependent on hyperglycemia

Since streptozotocin (STZ)-induced diabetes is a widely used model of painful diabetic neuropathy, the aim of the present study was to design a rational protocol to investigate whether the development of mechanical hypernociception induced by STZ depends exclusively on hyperglycemia. Male Wistar rats (180-200 g; N = 6-7 per group) received a single intravenous injection of STZ at three different doses (10, 20, or 40 mg/kg). Only the higher dose (40 mg/kg) induced a significant increase in blood glucose levels, glucose tolerance and deficiency in weight gain. However, all STZ-treated rats (hyperglycemic or not) developed persistent (for at least 20 days) and indistinguishable bilateral mechanical hypernociception that was not prevented by daily insulin treatment (2 IU twice a day, sc). Systemic morphine (2 mg/kg) but not local (intraplantar) morphine treatment (8 µg/paw) significantly inhibited the mechanical hypernociception induced by STZ (10 or 40 mg/kg). In addition, intraplantar injection of STZ at doses that did not cause hyperglycemia (30, 100 or 300 µg/paw) induced ipsilateral mechanical hypernociception for at least 8 h that was inhibited by local and systemic morphine treatment (8 µg/paw or 2 mg/kg, respectively), but not by dexamethasone (1 mg/kg, sc). The results of this study demonstrate that systemic administration of STZ induces mechanical hypernociception that does not depend on hyperglycemia and intraplantar STZ induces mechanical sensitization of primary sensory neurons responsive to local morphine treatment.

Neuroplasticidad y dolor / Neuroplasticity and pain

Todas las formas de dolor incluyen el desarrollo de un estado de hiperalgesia que ilustra la naturaleza dinámica y plástica de la sensación de dolor. La hiperalgesia es la característica más importante del proceso doloroso y es la expresión de la hipersensibilidad de las vías del dolor inducida por la sensibilización de los receptores periféricos que registran eventos dolorosos y de las neuronas que transmiten y procesan esta información sensorial al SNC. Los nociceptores periféricos se sensibilizan adquiriendo una mayor y a veces nueva capacidad de respuesta a los estímulos periféricos. Por otra parte, un proceso de plasticidad sináptica, del cual se ha identificado una variedad de componentes moleculares, interviene en la amplificación central de las señales de las aferencias nociceptivas, lo cual evoca la hipersensibilidad de las neuronas centrales. El resultado final es un proceso sensorial que, a pesar de haber sido puesto en marcha inicialmente por una lesión, puede no mantener una relación estrecha con la lesión original y convertirse en un estado de dolor crónico sin tener una causa definida.

All froms of pain include the development of a hyperalgesic state that illustrates the dynamic and plastic nature of pain sesation. Hyperalgesia is the most prominent feature of the pain process and is the expression of hypersensitivity of the pain pathway induced by the sensitization of the peripheral receptors that signal painful events and of the neurons that transmit and process this sensory information to the CNS. Peripheral nociceptors can be sensitized, acquiring enhanced, and sometimes novel, responsiveness to peripheral stimuli. On the other hand a process of synaptic plasticity, of which several molecular components have already been identified, mediates the central amplification of the afferent signals that leads to the hypersensitivity of central neurons. The final result is a sensory process that, although initially triggered by injury, may not keep a close relationship with the originating injury and develop into a chronic pain state in the absence of a defined cause.

Barostato rectal en el síndrome de intestino irritable / Rectal barostat in irritable bowel syndrome

Background: Many patients with irritable bowel syndrome (IBS) have lowered sensory thresholds to rectal distention when compared to control subjects, a phenomenon called visceral hypersensitivity. Aim: To investigate the usefulness of a rectal barostat as a diagnostic tool in IBS and if there are differences in visceral hypersensitivity in different groups of IBS patients. Patients and Methods: Ten healthy subjects and 19 IBS patients, defined using Rome II criteria (12 with constipation, three with diarrhea and four alternating between diarrhea and constipation), were studied. Sequential isobaric rectal distentions, from 2 mmHg up to a maximal pressure of 52 mmHg or when the patients reported pain, were carried out. Visceral hypersensitivity was defined as a pain threshold under 38 mmHg. Results: Only 26 percent of IBS patients had visceral hypersensitivity (16 percent and 43 percent of patients with IBS and constipation and IBS and diarrhea or alternating symptoms, respectively, p =NS). Pain threshold in controls, patients with IBS and constipation and patients with IBS and diarrhea or alternating symptoms was 43.8±6.6, 45.3±9.2 and 40.8±9.2 mmHg, respectively (p =NS). Conclusions: Our results do not support the usefulness of the electronic rectal barostat as a diagnostic method to diagnose IBS.

Protease-activated receptors and inflammatory hyperalgesia

Recent advances in basic science pointed to a role for proteinases, through the activation of proteinase-activated receptors (PARs) in nociceptive mechanisms. Activation of PAR1, PAR2 and PAR4 either by proteinases or by selective agonists causes inflammation inducing most of the cardinal signs of inflammation: swelling, redness, and pain. Sub-inflammatory doses of PAR2 agonist still induced hyperalgesia and allodynia while PAR2 has been shown to be implicated in the generation of hyperalgesia in different inflammatory models. In contrast, sub-inflammatory doses of PAR1 increases nociceptive threshold, inhibiting inflammatory hyperalgesia, thereby acting as an analgesic agent. PARs are present and functional on sensory neurons, where they participate either directly or indirectly to the transmission and/or inhibition of nociceptive messages. Taken together, the results discussed in this review highlight proteinases as signaling molecules to sensory nerves. We need to consider proteinases and the receptors that are activated by proteinases as important potential targets for the development of analgesic drugs in the treatment of inflammatory pain.

Hiperalgesia visceral e dor abdominal crônica: abordagem diagnóstica e terapêutica / Visceral hyperalgesia and chronic abdominal pain: diagnostic and therapeutic approach

JUSTIFICATIVA E OBJETIVOS: A dor abdominal crônica é uma das razões mais freqüentes para consulta médica. Não existe, entretanto, um protocolo bem estabelecido para a abordagem diagnóstica e, na maioria das vezes, essa investigação se torna uma prática médica onerosa e invasiva. A finalidade desta revisão é tentar esclarecer a fisiopatologia da dor visceral e estabelecer metas diagnósticas e terapêuticas, para portadores desta morbidade, baseada em critérios específicos. CONTEUDO: A dor abdominal crônica inespecífica ou funcional representa uma interação complexa entre distúrbio de motilidade, hipersensibilidade visceral e respostas neuroendócrina e psicossocial inadequadas. Mecanismos periféricos e centrais de nocicepção parecem estar envolvidos na hiperalgesia visceral. A abordagem diagnóstica requer uma avaliação minuciosa da história e exame clínico, levando em consideração os critérios de Roma II. Baseado nos mecanismos fisiopatológicos conhecidos, ou supostos, novas drogas vêm sendo pesquisadas, e algumas utilizadas mais recentemente, como os agonistas dos receptores 5-HT4 e bloqueadores dos canais de sódio, para o controle da dor abdominal. CONCLUSÕES: Os mecanismos fisiopatológicos da dor abdominal crônica, ainda não estão esclarecidos. A abordagem terapêutica e diagnóstica requer o conhecimento de tais mecanismos, bem como dos critérios de Roma II. Por outro lado, uma boa relação médico-paciente e a atuação de equipe intermultidisciplinar parecem fundamentais para melhorar a resposta ao tratamento instituído e a qualidade de vida do paciente.

BACKGROUND AND OBJECTIVES: Chronic abdominal pain is one of the most frequent reasons for medical consultation. There is, however, no well-established protocol for its diagnostic approach and, most of the times, investigation becomes an expensive and invasive medical practice. This review aimed at explaining visceral pain pathophysiology and establishing diagnostic and therapeutic goals for these patients, based on specific criteria. CONTENTS: Chronic nonspecific or functional abdominal pain is a complex interaction among impaired motility, visceral hypersensitivity and inadequate neuroendocrine and psychosocial responses. Peripheral and central nociception mechanisms seem to be involved in visceral hyperalgesia. Diagnosis requires detailed history and clinical evaluation, taking into consideration Rome II criteria. Based on known or assumed pathophysiological mechanisms, new drugs have been researched, and some have been more recently used to control abdominal pain, such as 5-HT4 receptor agonists and sodium channel blockers. CONCLUSIONS: Chronic pathophysiological abdominal pain mechanisms are still not well understood. Therapy and diagnosis require the understanding of such mechanisms, as well as of Rome II criteria. On the other hand, good patient-physician relationship and multidisciplinary team’s performance seem to be critical in improving treatment response and patients’ quality of life.

JUSTIFICATIVA Y OBJETIVOS: El dolor abdominal crónico es una de las razones más frecuentes para una consulta médica. No existe, entretanto, un protocolo bien establecido para el abordaje diagnóstico y, en la mayoría de las veces, esa investigación se hace una práctica médica onerosa e invasiva. La finalidad de esta revisión es tentar esclarecer la fisiopatología del dolor visceral y establecer metas diagnósticas y terapéuticas, para portadores de esta morbididad, fundamentada en criterios específicos. CONTENIDO: El dolor abdominal crónico inespecífico o funcional representa una interacción compleja entre disturbio de motilidad, hipersensibilidad visceral y respuestas neuroendócrina y psicosocial inadecuadas. Mecanismos periféricos y centrales de nocicepción parecen estar envueltos en la hiperalgesia visceral. El abordaje diagnóstico requiere una evaluación minuciosa de la historia y examen clínico, llevando en consideración los criterios de Roma II. Fundamentado en los mecanismos fisiopatológicos conocidos, o supuestos, nuevas drogas vienen siendo pesquisadas, y algunas utilizadas más recientemente, como los agonistas de los receptores 5-HT4 y bloqueadores de los canales de sodio, para el control del dolor abdominal. CONCLUSIONES: Los mecanismos fisiopatológicos del dolor abdominal crónico, aún no están esclarecidos. El abordaje terapéutico y diagnóstico requiere el conocimiento de tales mecanismos, así como de los criterios de Roma II. Por otro lado, una buena relación médico-paciente y la actuación de grupo intermultidiciplinar parecem fundamentais para mejorar la respuesta al tratamiento instituido y la calidad de vida del paciente.

Acute phenobarbital administration induces hyperalgesia: pharmacological evidence for the involvement of supraspinal GABA-A receptors

The aim of the present study was to determine if phenobarbital affects the nociception threshold. Systemic (1-20 mg/kg) phenobarbital administration dose dependently induced hyperalgesia in the tail-flick, hot-plate and formalin tests in rats and in the abdominal constriction test in mice. Formalin and abdominal constriction tests were the most sensitive procedures for the detection of hyperalgesia in response to phenobarbital compared with the tail-flick and hot-plate tests. The hyperalgesia induced by systemic phenobarbital was blocked by previous administration of 1 mg/kg ip picrotoxin or either 1-2 mg/kg sc or 10 ng icv bicuculline. Intracerebroventricular phenobarbital administration (5 æg) induced hyperalgesia in the tail-flick test. In contrast, intrathecal phenobarbital administration (5 æg) induced antinociception and blocked systemic-induced hyperalgesia in this test. We suggest that phenobarbital may mediate hyperalgesia through GABA-A receptors at supraspinal levels and antinociception through the same kind of receptors at spinal levels

Dolor orofacial: Características. Neurofisiología: mecanismos moduladores. Su vinculación con alteraciones del movimiento mandibular / Orofacial pain: Characteristics. Neurophysiology: modulating mechanisms. Its association with mandibular movement alterations

El dolor es el síntoma más habitual en la consulta odontológica y el factor causal de mayor importancia y frecuencia para que el paciente acuda en busca de asistencia. En los últimos años los neurólogos han hecho importantes avances en el estudio de los aspectos neurofisiológicos del dolor, referidos fundamentalmente a los mecanismos y sustancias que regulan su persistencia e intensidad. Lamentablemente gran parte de la información llega muy escasamente al odontólogo. Es interesante señalar también que tanto en el nivel pregrado como en el de posgrado son muy escasos los cursos con contenidos referidos a este tema. El objetivo de este trabajo es brindar una revisión básica y actualizada sobre distintos aspectos del síntoma dolor, a saber: nocicepción y dolor, diferencias conceptuales. Características: tipo de dolor: crónico-agudo, superficial, heterotópico. Neurofisiología: vías de conducción. Mecanismos modulares inhibitorios y de sensibilización, metaméricos y centrales. Sustancias que lo provocan: fenómenos de hiperalgesia, neuroplasticidad y persistencia del síntoma. Características del dolor inflamatorio, sensibilización periférica. El factor psicológico como modulador intrínseco del dolor vinculado al sufrimiento. Aspectos cognitivos, afectivo-emocionales y conductuales. Por último, algunos conceptos referidos a la posible asociación del dolor con alteraciones del movimiento mandibular

El tiempo y el pH de desaparición de la pirosis provocada por la perfusión ácida de esófago sería un indicador de hiperalgesia / Time and pH at the moment of disappearance of pyrosis induced by means of acid perfusion might indicate hyperalgesia

Objetivos: 1) Describir y comparar las características históricas del sintoma de pirosis con prueba de perfusión ácida positiva en el grupo total y según sexos; 2) describir los resultados de los estudios (clearance ácido estánder, número de episodios de reflujo en tiempos cortos de observación, tiempo de aparición de la pirosis durante la perfusión ácida, tiempo de desapacición del síntoma y pH del esófago en el momento de la desaparición); comparación por sexos; 3) comparar las diferencias de depuraniones estándar y de episodios de reflujo entre controles y pacientes; 4) correlacionar de factores condicionantes; 5) realizar las mismas evaluaciones descriptivas y comparativas en los subgrupos con hernia hiatal (H.H.) y sin ella. Trabajo prospectivo, descriptivo y comparativo, experimental, longitudinal, ciego simple, con muestra de control. Población y muestra: 15 pacientes de control (9 hombres, mujeres) y 50 pacientes con pirosis (23 hombres, 27 mujeres). Mayores de 18 años. Con H.H. o sin ella. Equiparables (diderencias en edad y sexo, p=NS). Consecutivos. Material y metodologia: Registro de datos históricos, endoscopia alta, 3 (tres) biopsias como mínimo, número de episodios de reflujo en 30 minutos de observación, clearance ácido estánder, medición de tiempo de perfusión, tiempo de desaparición del síntoma evocado y pH en que desaparece el síntoma...

Tratamiento local y segmentario de los trastornos dolorosos / Local and segmentary treatment of pain disorders

Objetivos: el propósito de este estudio fue evaluar el efecto analgésico producido por la aplicación de dos técnicas electroterapéuticas en formas simultáneas. Material y Método: pacientes, treinta pacientes (trece hombres y diecisiete mujeres) asistieron en forma ambulatoria a tratamientos los cuales fueron seleccionados en forma aleatoria. Método: los treinta pacientes fueron sometidos a dos sesiones de tratamiento con Tens de alta frecuencia y baja intensidad y con corriente interferencial de baja frecuencia y elevada intensidad durante cuarenta minutos. Se utilizó la escala visual análoga para medir el grado de dolor. Las sesiones se realizaron en días sucesivos. Resultados: el efecto analgésico al término de la primera y segunda sesión fue estadísticamente significativo con un p<0,05. Discusión: los mecanismos analgésicos que pueden estar implicados con la utilización de Tens y corriente interferencial en forma simultánea son diversos. Para el Tens se mencionan mecanismos dinorfínicos, inhibición de la liberación de sustancia P, activación autonómica, y placebo, entre otros. Para la corriente interferencial se menciona: activación autonómica, mecanismos similares a los de electroacupuntura de baja frecuencia y placebo. Conclusión: los mecanismos analgésicos fueron de rápida instalación en pacientes con patologías variadas

Neonatal treatment with naloxone causes permanent hyperalgesia in rats

The effect of treatment with naloxone early in life on pain responsiveness was studied in Wistar rats. Litters of six rats were divided equally into groups of 3 pups receiving daily naloxone (50 mg/kg, sc) and 3 pups receiving saline from the 3rd to 18th day of life. On days 30, 50, 70 and 90, one group of animals previously injected during suckling with naloxone (N = 21) and another with saline (N = 21) were submitted to the hot-plate test to measure the latency to paw licking. Other groups of rats also treated during suckling with naloxone (N = 13) and saline (N = 14) were assessed for the antinociceptive effect of morphine (10 mg/kg,sc). The naloxone group displayed a lower latency than the saline group in all test sessions and a diminished analgesic response to morphine. The results indicate that the use of naloxone (an antagonist opioid) during suckling, the brain growth spurt period, facilitates a long-lasting increased pain responsiveness and alters antialgesic mechanisms. In this respect, the opioid and non-opioid effects of naloxone on the ontogeny of neural systems should be taken into account