Opioid analgesics for nociceptive cancer pain: A comprehensive review.

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo-controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate-certainty to low-certainty evidence). Nonsteroidal anti-inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate-to-severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals.

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes. Survey study among the Dutch adult CNO cohort (n = 84/195 participated), including PAIN-detect for neuropathic pain, and the Central Sensitization Inventory (CSI), Fibromyalgia Rapid Screening Tool (FiRST), and ACTTION-APS Pain Taxonomy (AAPT) for nociplastic pain. Clinical characteristics and CNO-related bone pain scores were compared between patients with exclusive nociceptive pain and those with nociceptive pain plus neuropathic and/or nociplastic pain (mixed pain). 31% (95% CI 21-41) of patients classified as likely having neuropathic pain according to PAIN-detect. 53% (41-64) of patients displayed central sensitization on CSI, 61% (50-72) screened positive for fibromyalgia on FiRST and 14% (7-23) of patients fulfilled the AAPT criteria, all indicative of nociplastic pain. Mixed pain was associated with longer diagnostic delay (mean difference 2.8 years, 95% CI 0.4-5.2, p = 0.023), lower educational level (72% versus 20%, p < 0.001), and opioid use (37% versus 13%, p = 0.036). Despite comparable disease severity and extent, patients with mixed pain reported significantly higher CNO-related bone pain scores. This study demonstrates the high prevalence of mixed pain in adult CNO, in which neuropathic and nociplastic pain exist alongside nociceptive inflammatory bone pain. Disease burden in CNO may extend beyond inflammatory activity, highlighting the need for a multifaceted management approach.

Recent Advances in Management of Neuropathic, Nociceptive, and Chronic Pain: A Narrative Review with Focus on Nanomedicine, Gene Therapy, Stem Cell Therapy, and Newer Therapeutic Options.

PURPOSE OF REVIEW: This manuscript summarizes novel clinical and interventional approaches in the management of chronic, nociceptive, and neuropathic pain. RECENT FINDINGS: Pain can be defined as a feeling of physical or emotional distress caused by an external stimulus. Pain can be grouped into distinct types according to characteristics including neuropathic pain, which is a pain caused by disease or lesion in the sensory nervous system; nociceptive pain, which is pain that can be sharp, aching, or throbbing and is caused by injury to bodily tissues; and chronic pain, which is long lasting or persisting beyond 6 months. With improved understanding of different signaling systems for pain in recent years, there has been an upscale of methods of analgesia to counteract these pathological processes. Novel treatment methods such as use of cannabinoids, stem cells, gene therapy, nanoparticles, monoclonal antibodies, and platelet-rich plasma have played a significant role in improved strategies for therapeutic interventions. Although many management options appear to be promising, extensive additional clinical research is warranted to determine best practice strategies in the future for clinicians.

The effect of somatic pain and comorbid mental distress on oral health-related quality of life in orthodontic patients.

OBJECTIVES: The purpose of the present study was to evaluate the prevalence of somatic pain in orthodontic patients and determine whether somatic pain contributes to worsening oral health-related quality of life (OHRQoL) through the mediating effect of psychological discomfort. MATERIALS AND METHODS: Scale measurements and analyses were conducted on a cohort of 769 orthodontic outpatients, encompassing Patient Health Questionnaire-15-pain (PHQ-15-P), Hua-Xi Emotional-Distress Index (HEI), Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ), and Oral Health Impact Profile-14 (OHIP-14). RESULTS: Among the respondents, 56.3% (N = 433) reported somatic pain and 20.0% (N = 154) had mental discomfort based on PHQ-15-P and HEI scores. Patients with somatic pain symptoms had significantly higher scores of HEI and OHIP-14 (P < 0.001), and higher PHQ-15-P and HEI scores emerged as statistically significant predictors of lower OHIP-14 scores (P < 0.001). HEI scores which assessed anxiety and depression partially mediated the correlation between PHQ-15-P and OHIP-14 scores, of which anxiety accounted for 52.9% of the overall mediation effect, dominating the indirect effect. CONCLUSION: Orthodontic patients reporting somatic pains were at a significantly higher risk of worsening OHRQoL during treatment, and this adverse effect is partially mediated by anxiety and depression. CLINICAL RELEVANCE: Our findings highlight the necessity for the assessment of general health and mental well-being during orthodontic interventions. To prevent delays in treating general disorders and the potential failure of orthodontic treatments, we encourage increased attentiveness towards patients with somatic symptoms and consideration of the adverse effects of comorbid mental distress.

Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and positively influences pain sensitivity and work capacity.

The aim of the study was to investigate the effects of rat housing conditions-standard conditions, social isolation, environmental enrichment-and the subsequent reversal of these conditions on the vulnerability of the gastric mucosa to ulcerogenic stimuli, somatic pain sensitivity, and treadmill work capacity. Rats, aged 30 days, were placed in standard conditions (SC), social isolation (Is), and environmental enrichment (EE) for 4 weeks. Then half of each group underwent a reversal of housing conditions: SC rats were moved to Is, Is rats were placed in EE, EE rats were moved to Is, for 2 weeks. The other half served as a control with no change in their initial housing. Two weeks after the reversal, vulnerability of the gastric mucosa to ulcerogenic action of indomethacin (IM, 35 mg/kg, sc), somatic pain sensitivity (hot plate test), and work capacity (measured by the running distance on a treadmill) were assessed in control and reversed groups. Social isolation induced a proulcerogenic effect, increasing IM-induced gastric erosions, which was effectively reversed when rats were transferred to an environmental enrichment. Conversely, transferring rats from an environmental enrichment to social isolation exacerbated ulcerogenic action of IM. Somatic pain sensitivity and treadmill work capacity were also influenced by housing conditions, with environmental enrichment showing positive effects. The present findings show that social isolation of rats induces a proulcerogenic effect. Environmental enrichment reverses proulcerogenic action of social isolation on the gastric mucosa and increases resilience to pain stimuli and treadmill work capacity.

Translation and cross-cultural adaptation of Polish version of Neuropathic Pain Questionnaire (NPQ-PL) and its comparisons with different questionnaires.

AIM OF THE STUDY: The aim of this study was to assess the validity and reliability of the Polish version of the Neuropathic Pain Questionnaire (NPQ-PL), and to compare it to other diagnostic tools. CLINICAL RATIONALE FOR THE STUDY: Neuropathic pain is a burdensome condition, of which the exact prevalence is difficult to estimate. During initial screening, pain questionnaires are helpful in alerting clinicians about the need for further evaluation. MATERIAL AND METHODS: The NPQ-PL has been developed following the guidelines for translation and cultural adaptation. A total of 140 patients with chronic pain (ChP), 90 with neuropathic pain (NP), and 50 with nociceptive pain (NoP), were enrolled into this study. RESULTS: The study group consisted of 60.71% women and 39.29% men; the mean age of patients (standard deviation, SD) was 53.22 years (15.81), and the average NPQ-PL score (SD) was 0.49 (1.27). Statistically significant relationships were found between higher age distribution and greater pain intensity in the NP group compared to the NoP group. There were also significant differences in pain levels between people of different ages, with the predominance in the elderly. Cronbach's alpha coefficient of the whole questionnaire was 0.85 and the intraclass correlation coefficient (ICC) for test-retest reliability was 0.635. Using receiver-operating characteristic (ROC) curve analysis, the area under the curve (AUC) was 0.97 and the best cut-off value was 0.002, which resulted in the highest sensitivity (93.3%) and specificity (96.0%). CONCLUSIONS AND CLINICAL IMPLICATIONS: The NPQ-PL is a valid tool for discriminating between neuropathic and nociceptive pain. It can be used by physicians of various disciplines when assessing patients with ChP of various origins.

Protein Kinase A Inhibitor Attenuates the Antinociceptive Effect of NMDA-Receptor Channel Antagonists in the Capsaicin Test in Mice.

Acute nociceptive pain in mice caused by subcutaneous (intraplantar) injection of TRPV1 ion channel agonist capsaicin (1.6 µg/mouse) and the effects of protein kinase A inhibitor H-89 (0.05 mg/mouse, intraplantar injection) and NMDA receptor channel antagonists MK-801 (7.5 and 15 µg/mouse, topical application) and hemantane (0.5 mg/mouse, topical application) on the pain were assessed. MK-801 and hemantane were found to reduce the duration of the pain response. H-89 did not significantly affect the pain in animals, but preliminary administration of this drug abolished the antinociceptive effect of MK-801 (7.5 µg/mouse) and weakens the effect of hemantane (0.5 mg/mouse).

Deciphering nociplastic pain: clinical features, risk factors and potential mechanisms.

Nociplastic pain is a mechanistic term used to describe pain that arises or is sustained by altered nociception, despite the absence of tissue damage. Although nociplastic pain has distinct pathophysiology from nociceptive and neuropathic pain, these pain mechanisms often coincide within individuals, which contributes to the intractability of chronic pain. Key symptoms of nociplastic pain include pain in multiple body regions, fatigue, sleep disturbances, cognitive dysfunction, depression and anxiety. Individuals with nociplastic pain are often diffusely tender - indicative of hyperalgesia and/or allodynia - and are often more sensitive than others to non-painful sensory stimuli such as lights, odours and noises. This Review summarizes the risk factors, clinical presentation and treatment of nociplastic pain, and describes how alterations in brain function and structure, immune processing and peripheral factors might contribute to the nociplastic pain phenotype. This article concludes with a discussion of two proposed subtypes of nociplastic pain that reflect distinct neurobiological features and treatment responsivity.

Placebo treatment affects brain systems related to affective and cognitive processes, but not nociceptive pain.

Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study (N = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes.

[IPA's clinical expertise in the identification and assessment of somatic pain in schizophrenic patients]. / Expertise clinique de l'IPA PSM dans le repérage et l'évaluation de la douleur somatique chez les personnes schizophrènes.

Identifying and assessing somatic pain in people with schizophrenia remains a major public health issue for this vulnerable population. In France, Advanced Practice Nursing is developing, based on a practice built around clinical expertise. How can the clinical expertise of psychiatric and mental health APNs improve the identification and assessment of somatic pain in these patients, and thus help to improve their somatic health?

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice.

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

[Investigation of the effect of ethylmethylhydroxypyridine succinate on the effectiveness of non-steroidal anti-inflammatory drugs for visceral and somatic pain in mice and rats]. / Izuchenie vliyaniya etilmetilgidroksipiridina suktsinata na effektivnost' nesteroidnykh protivovospalitel'nykh preparatov pri vistseral'noi i somaticheskoi boli v eksperimente na myshakh i krysakh.

OBJECTIVE: To study the effect of ethylmethylhydroxypyridine succinate (EMHPS) on the analgesic effect of the non-selective cyclooxygenase (COX) inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib in models of acute visceral and somatic pain and to evaluate the possibility of using EMHPS in combination with COX inhibitors to reduce their doses while maintaining analgesic efficiency. MATERIAL AND METHODS: We studied the effect of EMHPS with a single oral administration on the analgesic effects of non-steroidal anti-inflammatory drugs (NSAIDs): the non-selective COX inhibitor diclofenac sodium and the selective COX-2 inhibitor etoricoxib - on models of acute visceral (vinegar writhing test) and somatic pain (formalin test and mechanical hyperalgesia during inflammation) in an experiment on mice and rats. RESULTS: In a model of acute visceral pain in mice, EMGPS (25-100 mg/kg) does not have a significant effect on its severity, but enhances the analgesic effect of diclofenac sodium (0.5 mg/kg) and etoricoxib (1 mg/kg). In the formalin test in rats, which simulates pain during surgical incisions (trauma), EMGPS (25 mg/kg) increases the severity of the analgesic effect of COX inhibitors (1 mg/kg), primarily by reducing pain in the acute phase caused by the effect of formalin on afferent neurons. In a model of mechanical hyperalgesia in rats caused by exudative inflammation after injection of a carrageenan solution into the paw, EMHPS enhances the effect of diclofenac to a greater extent than etoricoxib. CONCLUSION: The data obtained indicate the feasibility of a clinical study of the use of EMGPS in combination with NSAIDs for visceral and somatic pain in order to assess its ability to increase the therapeutic effect of NSAIDs.

Incorporación a nivel nacional de tecnología no invasiva para valoración del dolor y/o disconfort neonatal / Incorporation of non-invasive technology for the assessment of neonatal pain and/or discomfort at national level / Incorporação a nível nacional de tecnologia não invasiva para avaliação da dor e/ou desconforto neonatal

Introducción: la exposición a estímulos dolorosos y estrés en la etapa neonatal, sin un correcto tratamiento, tiene consecuencias a corto y largo plazo. El diagnóstico adecuado es un desafío, ya que las escalas clínicas son subjetivas y se requieren herramientas de detección con mejor objetividad y capacidad de interpretación del disconfort/dolor neonatal. Newborn Infant Parasympathetic Evaluation (NIPE™) es una tecnología no invasiva de monitorización continua del dolor en neonatos, desarrollada recientemente dada la dificultad de objetivar el dolor mediante los métodos convencionales en la práctica clínica. Esta tecnología se basa en el análisis de la variabilidad de la frecuencia cardíaca (FC), lo que permite aproximarse a la actividad del sistema parasimpático. Objetivos: el objetivo de esta investigación fue valorar el disconfort en un modelo de cerdo recién nacido (RN) y en humanos neonatos expuestos a maniobras nociceptivas con la utilización de tecnología no invasiva (NIPE), en la maternidad del Hospital Universitario. Material y métodos: se realizó un estudio observacional, longitudinal, en seis cerdos RN, anestesiados, monitorizados hemodinámicamente y sometidos a un procedimiento quirúrgico mayor (toracotomía lateral izquierda con abordaje cardíaco, pericardiostomía y acceso vascular pulmonar transventricular derecho) y 12 procedimientos mínimamente invasivos de la práctica clínica habitual, como vacunación BCG, hemoglucotest y pesquisa, que generan un estímulo nociceptivo en ocho RN de término sanos. Se incluyeron RN sanos de término (EG entre 37-41 semanas más seis días) internados en el alojamiento conjunto madre-hijo, se excluyeron de la muestra los RN que presentaron alguna patología y aquellos cuyos padres no aceptaron la participación en el estudio. Resultados: se comparó la variabilidad de la FC mediante detección automatizada (NIPE™) para estimación objetiva del dolor/disconfort. Se comparó en la clínica con una escala validada y ampliamente utilizada en neonatos: Premature Infant Pain Profile (PIPP). Para valorar la asociación entre variables NIPE™ y FC se utilizaron correlación de Spearman, el test de Kruskall-Wallis o test de chi cuadrado con corrección de Fisher, según correspondiera. Se encontró una correlación negativa entre FC y NIPE™ tanto para el grupo de neonatos humanos (r=-1; p=0,008) como para el modelo animal (r=-0,6; p=0,0004). No se encontró asociación significativa entre NIPE™ y la escala PIPP. La variación entre valores de NIPE™ pre y posestímulo en RN humanos fue significativa (p=0,008). Conclusiones: determinamos que en ambos escenarios explorados los valores de NIPE™ descienden ante estímulos nociceptivos y los cambios en la FC se relacionan con sus valores, independientemente de la especie o la agresividad de la maniobra. Este trabajo es el primero a nivel nacional incorporando el uso de esta tecnología, creemos que tendrá impacto en la forma de evaluar y abordar el dolor por parte de los equipos asistenciales y de experimentación.

Introduction: exposure to painful stimuli and stress in the neonatal stage, without correct treatment, has short and long-term consequences. Proper diagnosis is a challenge since clinical scales are subjective, and we require more objective screening tools and a better ability to interpret neonatal discomfort/pain. Newborn Infant Parasympathetic Evaluation (NIPE™) is a non-invasive technology for continuous pain monitoring in neonates, recently developed given the difficulty to objectify pain using conventional methods in clinical practice. This technology is based on the analysis of heart rate variability (HR), which allows us to approximate the activity of the parasympathetic system. Objectives: the objective of this research was to assess discomfort in a newborn pig model (NB) and in human neonates exposed to nociceptive maneuvers with the use of non-invasive technology (NIPE), in the maternity ward of the University Hospital. Material and methods: an observational, longitudinal study was carried out in 6 NB pigs, anesthetized, hemodynamically monitored and subjected to a major surgical procedure (left lateral thoracotomy with cardiac approach, pericardiostomy and right trans ventricular pulmonary vascular access) and 12 minimally invasive procedures, from clinical practice. routine such as BCG vaccination, hemoglucotest and screening, which generate a nociceptive stimulus in 8 healthy term newborns. Healthy term newborns (GA between 37-41 weeks plus 6 days) admitted to the mother-child joint accommodation were included, We excluded those NB patients who presented some pathology or whose parents did not accept participation in the study. Results: HR variability was compared using automated detection (NIPETM) for objective estimation of pain/discomfort. It was compared in the clinic with a validated and widely used scale in neonates: Premature Infant Pain Profile (PIPP). We used the Spearman's correlation, the Kruskall-Wallis test or the Chi square test with Fisher's correction to assess the association between NIPE™ variables and HR, as needed. A negative correlation was found between HR and NIPETM for both the group of neonates. humans (r=-1; p=0.008) and for the animal model (r=-0.6; p=0.0004). No significant association was found between NIPETM and the PIPP scale. The variation between pre- and post-stimulus NIPE™ values in human NBs was significant (p=0.008). Conclusions: we conclude that in both scenarios explored, NIPE™ values decrease when faced with nociceptive stimuli and changes in HR are related to its values, regardless of the species or the aggressiveness of the maneuver. This paper is the first at a national level to incorporate the use of this technology, we believe it will have an impact on the way pain is assessed and addressed by healthcare and experimental teams.

Introdução: a exposição a estímulos dolorosos e ao estresse na fase neonatal, sem tratamento correto, traz consequências a curto e longo prazo. O diagnóstico adequado é um desafio, uma vez que as escalas clínicas são subjetivas e são necessárias ferramentas de triagem com melhor objetividade e capacidade de interpretar o desconforto/dor neonatal. A Avaliação Parassimpática do Recém-Nascido (NIPE™) é uma tecnologia não invasiva para monitoramento contínuo da dor em neonatos, desenvolvida recentemente devido à dificuldade de objetivar a dor usando métodos convencionais na prática clínica. Esta tecnologia baseia-se na análise da variabilidade da frequência cardíaca (FC), o que nos permite aproximar a atividade do sistema parassimpático. Objetivos: o objetivo desta pesquisa foi avaliar o desconforto em recém-nascido modelo suíno (RN) e em neonatos humanos expostos a manobras nociceptivas com uso de tecnologia não invasiva (NIPE), na maternidade do Hospital Universitário. Material e métodos: foi realizado um estudo observacional, longitudinal, em 6 suínos RN, anestesiados, monitorados hemodinamicamente e submetidos a um procedimento cirúrgico de grande porte (toracotomia lateral esquerda com abordagem cardíaca, pericardiostomia e acesso vascular pulmonar transventricular direito) e 12 procedimentos minimamente invasivos, da prática clínica. rotina como vacinação BCG, hemoglicoteste e triagem, que geram estímulo nociceptivo em 8 recém-nascidos a termo saudáveis. Foram incluídos recém-nascidos a termo saudáveis (IG entre 37-41 semanas mais 6 dias) internados no alojamento conjunto mãe-filho, foram excluídos do A amostra incluiu RNs que apresentavam alguma patologia e aqueles cujos pais não aceitaram a participação no estudo. Resultados: a variabilidade da FC foi comparada por meio de detecção automatizada (NIPETM) para estimativa objetiva de dor/desconforto. Foi comparado na clínica com uma escala validada e amplamente utilizada em neonatos: Premature Infant Pain Profile (PIPP). Para avaliar a associação entre as variáveis do NIPE™ e a FC, utilizou-se a correlação de Spearman, o teste de Kruskall-Wallis ou o teste Qui-quadrado com correção de Fisher, conforme apropriado. Foi encontrada correlação negativa entre a FC e o NIPETM para ambos os grupos de neonatos. (r=-1; p=0,008) e para o modelo animal (r=-0,6; p=0,0004). Não foi encontrada associação significativa entre o NIPETM e a escala PIPP. A variação entre os valores de NIPE™ pré e pós-estímulo em RN humanos foi significativa (p=0,008). Conclusões: concluímos que em ambos os cenários explorados, os valores do NIPE™ diminuem diante de estímulos nociceptivos e as alterações na FC estão relacionadas aos seus valores, independente da espécie ou da agressividade da manobra. Este trabalho é o primeiro a nível nacional a incorporar a utilização desta tecnologia, acreditamos que terá impacto na forma como a dor é avaliada e abordada pelas equipas de saúde e experimentais.

Nociceptive Profile and Analgesic use of Patients Submitted to Rotator Cuff Repair Surgery: A Prospective Cohort / Perfil nociceptivo e uso de analgésicos em pacientes submetidos à cirurgia de reparo do manguito rotador: Coorte prospectiva

Abstract Objective This study aimed to evaluate the nociceptive profile and the intake of analgesic drugs of patients submitted to rotator cuff repair surgery. Also, to evaluate the nociceptive thresholds and the integrity of the descending inhibitory system, pain catastrophism and prevalence of nociceptive or neuropathic pain. Methods Approved by the Ethics Committee of La Salle University (1.325.433/2015). 40 patients (>18 years old) who underwent rotator cuff repair surgery (divided in small and large injuries) were recruited. The used instruments were: Sociodemographic Questionnaire, Functional Pain Scale, Visual Analogue Scale (VAS), Quantitative Sensory Test (QST) and Conditioned Pain Modulation Task (CPM). Results Patients had a significant difference in pain thresholds QST heat (independent samples t test) and quality of sleep, mood and anxiety (paired t test) in groups preoperative. There was a significant correlation between preoperative CPM and postoperative VAS (Pearson Correlation). It was observed that, in preoperative, 38 patients used analgesics continuously. Besides that, in postoperative, use of opioid drugs was higher in patients with small injury (13 patients) than in those with large injury (9 patients). Conclusion Therefore, patients with rotator cuff injuries did not present alterations in the descending inhibitory system, but showed alterations in pain thresholds, which may interfere in the postoperative period and still be related to the consumption of analgesics.

Resumo Objetivo O objetivo deste estudo foi avaliar o perfil nociceptivo e o uso de analgésicos em pacientes submetidos à cirurgia de reparo do manguito rotador. Além disso, os limiares nociceptivos e a integridade do sistema inibidor descendente, o catastrofismo da dor e a prevalência de dor nociceptiva ou neuropática também foram analisados. Métodos Este estudo foi aprovado pelo Comitê de Ética da Universidade La Salle (1.325.433/2015). Quarenta pacientes (maiores de 18 anos) submetidos à cirurgia de reparo do manguito rotador (divididos entre aqueles com lesões pequenas e grandes) participaram do estudo. Os instrumentos utilizados foram o Questionário Sociodemográfico, a Escala Funcional de Dor, a Escala Visual Análoga (EVA), o Teste Sensorial Quantitativo (QST) e a Tarefa de Modulação Condicionada da Dor (CPM). Resultados Os pacientes apresentaram diferenças significativas nos limiares de dor e QST de calor (teste t de amostras independentes) e qualidade do sono, humor e ansiedade (teste t pareado) nos grupos pré-operatórios. Houve uma correlação significativa entre CPM pré-operatória e EVA pós-operatória (correlação de Pearson). Observou-se que, no período pré-operatório, 38 pacientes utilizavam analgésico de forma contínua. Além disso, no período pós-operatório, o uso de opioides foi maior nos pacientes com lesões pequenas (13 pacientes) em comparação àqueles com lesões grandes (nove pacientes). Conclusão Os pacientes com lesão do manguito rotador não apresentaram alterações no sistema inibidor descendente, mas sim alterações nos limiares de dor, o que pode interferir no período pós-operatório e estar relacionado ao consumo de analgésicos.

Estimación del dolor durante el perioperatorio: Una revisión narrativa de los dispositivos disponibles / Estimative pain measurement during perioperative period: a review of current available devices

Pain is a complex subjective organic function which is influenced by sensorial, emotional, cognitive and behavioral elements. Despite the wide offer of pain measurement devices in the perioperative period, none of them is completely validated for their transverse use in the anesthetic practice. The aim of this review is to present the existing devices for objective pain evaluation during the perioperative period along with the scientific evidence supporting each of them. Articles from the PubMed/MEDLINE literature search engine were reviewed. As result, 37 articles were selected due to its relevance, from which 13 pain assessment devices were described, regarding its clinical relevance as well as the amount of scientific evidence found. Among them are ANI, NOL, pupillometry, qNOX, and others. The nociceptive measurement performed by most of these is based mainly on the evaluation of the autonomic nervous system activity and variations of the electroencephalographic signal. However, it is not possible to recommend any particular device. This review aims to offer a broad overview of the available options in order to estimate the role that each of them could play in clinical anesthesiology practice.

El dolor es una experiencia subjetiva compleja en la que inciden elementos sensoriales, emocionales, cognitivos y conductua- les. A pesar de una amplia oferta de dispositivos para medir dolor en el perioperatorio, hoy no existe un instrumento de medición de analgesia validado y utilizado transversalmente en la práctica anestésica. El objetivo de esta revisión es presentar las actuales opciones disponibles para la medición del dolor agudo utilizadas en el período perioperatorio junto con la evidencia científica que respalda cada una de ellas. Se realizó una revisión de la literatura utilizando como fuente de búsqueda bibliográfica la base de datos MEDLINE/pubMed utilizando términos MESH. Como resultado, se seleccionaron 37 artículos de acuerdo a su importancia, a partir de los cuales se describen 13 dispositivos de valoración nociceptiva, a propósito de su relevancia clínica como también por la cantidad de evidencia científica encontrada. Entre ellos destacan ANI, NOL, pupilometría, qNOX, entre otros. La medición nociceptiva realizada por la mayoría de estos se basa principalmente en la evaluación de la actividad del sistema nervioso autónomo y variaciones de la señal electroencefalográfica. Sin embargo, no es posible recomendar algún dispositivo en particular. Esta revisión pretende ofrecer una visión amplia de las opciones disponibles con el fin de estimar el rol que cada uno de ellos podría desempeñar en la práctica clínica anestesiológica.

Importancia semiológica del dolor durante etapas de un proceso inflamatorio pulpar / Semiological importance of pain during the stages of a pulpal inflammation process

RESUMEN Introducción: Existe la tentativa de realizar un diagnóstico del proceso inflamatorio pulpar, basado en el aspecto histopatológico, el cual es irreal pues no se puede comparar estos hallazgos con los clínicos. Resulta más objetivo y confiable, analizar las características del dolor que expresa la evolución pulpar en cada etapa y establecer un diagnóstico certero que permita precisar el tipo de tratamiento. Objetivo: Interpretar el curso de un proceso inflamatorio pulpar a través de las variables asociadas a estímulos nociceptivos. Métodos: Se realizó una revisión bibliográfica sobre las variables en relación con el dolor y su asociación con un estado inflamatorio pulpar. Se analizaron 24 artículos científicos en relación con el dolor pulpar, se escogieron 15 por ser los más afines al propósito perseguido, y todos corresponden a los últimos 5 años, publicados en revistas internacionales y nacionales. PubMed se utilizó como fuente fundamental de búsqueda; otras bases de datos también consultadas fueron Lilacs, Hinari y Medline. Análisis e integración de la información: Las condiciones pulpares se clasifican como: pulpitis reversible, transicional, irreversible y pulpa necrótica. La semiología del dolor se sustenta en cuatro variables básicas asociadas a los estímulos nociceptivos que son: cualidad del dolor pulpar puede ser punzante o continuo, su curso intermitente o continuo, su localización limitado a una región de la boca, irradiado y referido, y su intensidad considerada como leve, moderado o severo. Conclusiones: Las variables asociadas a los estímulos nociceptivos revisten importancia semiológica, pues permiten valorar las manifestaciones dolorosas por las que transita un proceso inflamatorio pulpar(AU)

ABSTRACT Introduction: Attempts have been made to diagnose the pulpal inflammatory process based on its histopathological features, but to no avail, for these findings cannot be compared with clinical results. It would be more objective and reliable to analyze the characteristics of the pain expressing the pulpal evolution at each stage and establish an accurate diagnosis allowing the choice of the type of treatment to be indicated. Objective: Interpret the course of a pulpal inflammatory process through variables associated to nociceptive stimuli. Methods: A bibliographic review was conducted about the study variables with respect to pain and its association to a pulpal inflammatory state. A total 24 scientific papers were analyzed which dealt with pulpal pain, of which 15 were selected for being the most closely related to the goal pursued and having been published in international and national journals in the last five years. PubMed was the main source searched, while other databases such as Lilacs, Hinari and Medline were also consulted. Data analysis and integration: Pulpal conditions are classified into reversible, transitional, irreversible pulpitis and necrotic pulp. Pain semiology is based on the following four basic variables associated to nociceptive stimuli: pulpal pain quality (sharp or continuous), course (intermittent or continuous), location (limited to a region in the mouth, radiating or referred) and intensity (mild, moderate or severe). Conclusions: The variables associated to nociceptive stimuli are semiologically important, for they make it possible to evaluate the painful manifestations gone through by a pulpal inflammatory process(AU)

Mecanismos de modulación central del dolor: revisión de la literatura / Mechanisms of central pain modulation: literature review

RESUMEN: La percepción del dolor resulta de múltiples y dinámicos mecanismos en el sistema nervioso central (SNC) y periférico que inhiben o facilitan el estímulo y respuesta nociceptiva. Sin embargo, la principal capacidad de modulación esta a cargo del SNC. Los estímulos nociceptivos son detectados por terminaciones nerviosas libres de neuronas periféricas que sinaptan con neuronas aferentes secundarias de la médula espinal. Luego estas fibras decusan para formar las vías nociceptivas ascendentes. Una vez alcanzadas las estructuras subcorticales, se activan las neuronas del tálamo, quienes envían el estímulo hacia la corteza somatosensorial, desencadenando la percepción consciente del dolor y activando el sistema inhibitorio descendente. Para que la modulación nociceptiva se realice, es necesaria la participación de diversas sustancias o neurotransmisores que conectan áreas del SNC especializadas. Por lo tanto, el objetivo de este estudio fue realizar una revisión de la literatura respecto de los mecanismos que participan en los procesos de modulación central del dolor.

SUMMARY: Pain perception results from multiple and dynamic mechanisms in the central nervous system (CNS) and peripheral nervous system that inhibit or facilitate stimulation and nociceptive response. However, neuromodulation is mainly a function of the CNS. Nociceptive stimulus is detected by peripheral neurons receptors that synapse with the secondary afferent neurons of the spinal cord. These fibers cross to conform the ascending nociceptive pathways. Once the subcortical structures are reached, the thalamus`s neurons are activated; the thalamus send the stimulus to the somatosensory cortex, triggering the conscious perception of pain and activating the descending inhibitory system. For the nociceptive modulation to be carried out, the participation of various substances or neurotransmitters that connect specialized CNS areas is necessary. Therefore, the aim of this study was to review the literature regarding the mechanisms involved in central pain modulation processes.

Dolor psíquico: una mirada a su condición actual / Psychic pain: a look to its current condition

Resumen No obstante, el dolor ha permanecido ligado a la existencia humana y que la asistencia al dolor es una de las principales funciones de los equipos de salud, el dolor psíquico no ha estado presente en la formación médica ni en la investigación. En el presente estudio se plantearon dos preguntas: ¿Cuál es el estado actual de la investigación considerando las perspectivas psicológicas y neurobiológicas del dolor psicológico? y ¿qué lugar ocupa el dolor psicológico en la asistencia actual de los pacientes? Los objetivos fueron: 1) Revisar la significación del dolor en su perspectiva histórica y su relación con la existencia humana; 2) Examinar las bases neurobiológicas del dolor físico y psíquico; 3) Reflexionar acerca del lugar que le cabe al dolor psíquico en los programas de cuidados paliativos del dolor. Como metodología se revisó la literatura publicada en Medline, Scopus y Scielo tomando las palabras claves: Dolor Psíquico, Dolor Mental y Dolor Emocional. Se revisan las razones por las cuales el dolor psíquico ha permanecido postergado, considerando que la experiencia del dolor es una experiencia psíquica debido a que puede haber dolor psíquico sin dolor físico, pero no al revés. El dolor psíquico puede ser tan real como otras formas de dolor más aun considerando que puede ser tan severo como para exponer a una persona al riesgo suicida. Se analizan las estructuras involucradas en el dolor psíquico y físico y se comenta acerca del rol de los médicos en su deber de aliviar el dolor.

Although pain has been present trough human history and that its assistance is one of the most important activities of health teams, psychic pain hasn't been present properly neither in medical education nor research. In order to assess this topic the author has carried out a review following these two questions: What is the state of the art considering psychological and neurobiological perspectives of psychic pain? and which place is occupying psychic pain in the current assistance of patients? The proposed objectives were: 1) To evaluate historical aspects of pain and its place in human life; 2) To evaluate neurobiological basis of psychic and somatic pain and 3) To reflect about the place psychic pain has currently in Paliative Care Programs. The methodology was the review of current literature published in Medline, Scopus and Scielo considering the following key words: Psychological Pain, Mental Pain and Emotional Pain. Special consideration is given to how this topic has been postponed and the reasons for this situation, considering that the whole experience of pain is psychological, as there may be psychical pain without physical pain but not otherwise. Psychic pain is not less real than other kind of pain; it may be even more severe as to put a person at risk of suicide. Mention is made about the boundaries between physical and psychic pain considering that they are not clear, as they involve similar structures. The role of medical doctors in helping to alleviate pain of patients is addressed.

Preliminary molecular characterization of a proinflammatory and nociceptive molecule from the Echinometra lucunter spines extracts

Background Sea urchins are animals commonly found on the Brazilian shoreline, being Echinometra lucunter the most abundant species. Accidents caused by E. lucunter have been reported as one of the most frequent in Brazil, and are characterized by intense pain and inflammation, consequence of spine puncture in the skin. In order to characterize such toxic effects, we isolated one molecule that caused inflammatory and nociceptive effects. Methods E. lucunter specimens were collected without gender distinction. Spines were removed and molecules were extracted, fractionated by RP-HPLC and assayed for inflammatory and nociceptive activity, in a biological-driven fractionation way, until the obtainment of one active molecule and its subsequent analysis by mass spectrometry (MS and MS/MS). For inflammation, intravital microscopy was performed on the mouse cremaster muscle, in order to evaluate rolled, adherent and migrating leukocytes. Paw edema was also evaluated. For the nociceptive activity, the paw pressure test was performed in rats. Results One molecule could be isolated and related to the inflammatory and nociceptive activity. Regarding inflammation, increase in adherent and migrating cells was observed in the cremaster muscle after the administration of the molecule. Corroborating the inflammatory response, paw edema was also observed, although only in 20% of controls and 20 min after injection. Additionally, this molecule was able to decrease significantly the pain threshold, characterizing hyperalgesia. This molecule was analyzed by mass spectrometry, and according to the exact molecular mass, isotopic distribution and fragmentation profile, it was possible to propose the molecular formula C29H48N3O10. Conclusions One isolated molecule from the spine extract of E. lucunter is able to elicit inflammation and hypernociception in animal models, which is in agreement with the effects observed in sea urchin accidents.(AU)

Composition and biological activities of the aqueous extracts of three scleractinian corals from the Mexican Caribbean: Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea

Background: Scleractinian corals (stony corals) are the most abundant reef-forming cnidarians found in coral reefs throughout the world. Despite their abundance and ecological importance, information about the diversity of their toxins and their biological activities is very scarce. In this study, the chemical composition and the biological activities of the aqueous extracts of Pseudodiploria strigosa, Porites astreoides and Siderastrea siderea, three scleractinian corals from the Mexican Caribbean, have been assessed for the first time. Methods: Toxicity of the extracts was assessed in crickets; the presence of cytolysins was detected by the hemolysis assay; the vasoconstrictor activity was determined by the isolated rat aortic ring assay; the nociceptive activity was evaluated by the formalin test. The presence of phospholipases A2 (PLA2), serine proteases, and hyaluronidases was determined by enzymatic methods. Low-molecular-weight fractions were obtained by gel filtration chromatography and ultrafiltration. Results: Extracts from the three species were toxic to crickets, induced hemolysis in human and rat erythrocytes, produced vasoconstriction on isolated rat aortic rings, and presented phospholipase A2 and serine-protease activity. Despite the fact that these corals are not considered to be harmless to humans, the extracts generated significant nociceptive responses. The matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis of the low-molecular-weight fractions revealed the presence of peptides within a mass range of 3000 to 6000 Da. These fractions were toxic to crickets and two of them induced a transitory vasoconstrictor effect on isolated rat aortic rings. Conclusion: This study suggests that scleractinian corals produce low-molecular-weight peptides that are lethal to crickets and induce vasoconstriction.(AU)