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).

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.

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.

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.

[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?

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.

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.

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.

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.

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.

Reliability of the Pen-on-Paper Pain Drawing Analysis Using Different Scanning Procedures.

INTRODUCTION: Pen-on-paper pain drawing are an easily administered self-reported measure that enables patients to report the spatial distribution of their pain. The digitalization of pain drawings has facilitated the extraction of quantitative metrics, such as pain extent and location. This study aimed to assess the reliability of pen-on-paper pain drawing analysis conducted by an automated pain-spot recognition algorithm using various scanning procedures. METHODS: One hundred pain drawings, completed by patients experiencing somatic pain, were repeatedly scanned using diverse technologies and devices. Seven datasets were created, enabling reliability assessments including inter-device, inter-scanner, inter-mobile, inter-software, intra- and inter-operator. Subsequently, the automated pain-spot recognition algorithm estimated pain extent and location values for each digitized pain drawing. The relative reliability of pain extent analysis was determined using the intraclass correlation coefficient, while absolute reliability was evaluated through the standard error of measurement and minimum detectable change. The reliability of pain location analysis was computed using the Jaccard similarity index. RESULTS: The reliability analysis of pain extent consistently yielded intraclass correlation coefficient values above 0.90 for all scanning procedures, with standard error of measurement ranging from 0.03% to 0.13% and minimum detectable change from 0.08% to 0.38%. The mean Jaccard index scores across all dataset comparisons exceeded 0.90. CONCLUSIONS: The analysis of pen-on-paper pain drawings demonstrated excellent reliability, suggesting that the automated pain-spot recognition algorithm is unaffected by scanning procedures. These findings support the algorithm's applicability in both research and clinical practice.

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.

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.

Memory surfacing among veterans with PTSD receiving hyperbaric oxygen therapy.

Introduction: Growing evidence demonstrates that hyperbaric oxygen therapy (HBO2) induces neuroplasticity and can benefit individuals with post-traumatic stress disorder (PTSD). The aim of the current study was to evaluate the rate and pattern of memory surfacing during the course of HBO2 among veterans with combat-related PTSD. Methods: In a post-hoc analysis of a prospective study of the effect of HBO2 on PTSD symptoms in veterans, we evaluated the rate and character of memory surfacing during the course of HBO2 treatment. The treatment consisted of 60 daily 90-minute sessions, at 2 atmospheres absolute (ATA) pressure and 100% oxygen. Results: For 10 (35.7%) of the 28 participants, surfacing of new memories was reported during the HBO2 treatment course. Memories surfaced mainly during the second month of the treatment, at the mean session of 30.5±13.2. For 9 of these 10 participants, prodromal symptoms such as distress, anxiety, or worsening depression were documented; and in four, somatic pain was reported prior to memory surfacing. The pain and distress of memory surfacing resolved over the course of one to 10 days. Discussion: Among individuals with PTSD, the surfacing of new memories, accompanied by emotional distress and somatic pain, is common during HBO2. The surfacing of memories sheds light on the biological effect of HBO2 on the brain sequela of PTSD. It is highly important that in treating patients for any indication, HBO2 medical teams be aware and capable of addressing memory surfacing, particularly in those with a history of trauma.

[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.

Investigation for Factors Affecting Body Perception Disturbance in Patients with Low Back Pain by Mechanism-Based Classification of Pain: A Cross-Sectional Study.

Background: Central sensitization is a pathophysiological cause of chronic low back pain and is linked with psychosocial factors. The association between central sensitization (CS) and body perception disturbance is currently unclear, and no prior studies have investigated this relationship in patients with acute or subacute low back pain. The objective of this study was to investigate potential factors that influence body perception disturbance using a mechanistic classification of low back pain. Methods: This cross-sectional study was conducted at the time of initial physical therapy in patients with low back pain. During the study period, 169 patients were recruited. Pain intensity, disease duration, disability, CS, and body perception disturbance were evaluated. Patients were divided into three groups according to the pathology of low back pain, and multivariate analysis was used to examine factors affecting body perception disturbance. The dependent variable was Fremantle Back Awareness Questionnaire (FreBAQ); the independent variables were age, gender, BMI, VAS, disease duration, RDQ, and CS Inventory-9 (CSI-9). Results: A total of 117 patients were included in our analysis. According to the mechanistic classification of pain, 66 (56.4%), 36 (30.8%), and 15 (12.8%) patients were categorized as having nociceptive pain (NP), peripheral neuropathic pain (PNP), and CS pain (CSP), respectively. Patients with PNP or CSP were significantly older than those with NP (p < 0.01). FreBAQ and RDQ scores were significantly higher in patients with CSP than those with NP (p < 0.05). The results of multiple regression analyses indicated that CSI-9 scores were significantly associated with FreBAQ (p < 0.01). Conclusion: Patients with CS syndrome and low back pain tend to have higher CSI-9 scores and be older. Body perception disturbance is influenced by CS or CS syndrome, regardless of the stage of low back pain, suggesting that patients with chronic low back pain tend to have low body image.

Rapid improvements and subsequent effects in major depressive disorder patients with somatic pain using rTMS combined with sertraline.

This study aims to explore changes in depression and pain for major depressive disorder (MDD) patients with somatic pain after repetitive transcranial magnetic stimulation (rTMS) using the event-related potentials (ERPs) technique. Eighty MDD patients with somatic pain were randomly assigned to drug therapy (DT) and combined therapy (CT) groups. CT group underwent intermittent theta burst stimulation over the left dorsolateral prefrontal cortex (DLPFC) with 800 pulses and 1 Hz over the right DLPFC with 800 pulses, 5 times a week for 3 weeks. All patients were given sertraline at 50-100 mg per day. All subjects were evaluated at baseline and at weeks three and six of therapy using the Hamilton Rating Scale for Depression (HAMD), Hamilton Anxiety Scale (HAMA), and Numerical Rating Scales (NRS), and the latency and amplitude of P300 and mismatch negativity (MMN) were measured. There were no significant differences in all indices between groups at baseline. At 3 weeks, HAMD subscale scores of Cognitive Impairment and NRS scores were significantly lower in the CT group than in the DT group. At 6 weeks, NRS and HAMD total scores in the CT group decreased significantly in the CT group compared with the DT group, especially for anxiety and pain, and the MMN and P300 latencies and P300 amplitude showed greater improvements. Our findings highlight that rTMS in combination with antidepressants is a rapid method of symptom improvement in patients with somatic pain with MDD and is helpful for cognitive impairment and anxiety.

The Ca2+ channel ORAI1 is a regulator of oral cancer growth and nociceptive pain.

Oral cancer causes pain associated with cancer progression. We report here that the function of the Ca2+ channel ORAI1 is an important regulator of oral cancer pain. ORAI1 was highly expressed in tumor samples from patients with oral cancer, and ORAI1 activation caused sustained Ca2+ influx in human oral cancer cells. RNA-seq analysis showed that ORAI1 regulated many genes encoding oral cancer markers such as metalloproteases (MMPs) and pain modulators. Compared with control cells, oral cancer cells lacking ORAI1 formed smaller tumors that elicited decreased allodynia when inoculated into mouse paws. Exposure of trigeminal ganglia neurons to MMP1 evoked an increase in action potentials. These data demonstrate an important role of ORAI1 in oral cancer progression and pain, potentially by controlling MMP1 abundance.

Experimental traumatic occlusion drives immune changes in trigeminal ganglion.

We previously demonstrated that experimental traumatic occlusion (ETO) induces a long-lasting nociceptive response. These findings were associated with altered neuronal patterns and suggestive satellite glial cell activation. This study aimed to elucidate the activation of satellite glial cells following ETO in the trigeminal ganglion. Moreover, we explored the involvement of resident and infiltrating cells in trigeminal ganglion in ETO. Finally, we investigated the overexpression of purinergic signaling and the CX3CL1/CX3CR1 axis. RT-qPCR and electrophoresis showed overexpression of GFAP in the trigeminal ganglion (TG), and immunohistochemistry corroborated these findings, demonstrating SGCs activation. ELISA reveals enhanced levels of TNF-α and IL-1ß in TG after 28 d of ETO. In trigeminal ganglia, ETO groups improved the release of CX3CL1, and immunohistochemistry showed higher CX3CR1+ -immunoreactive cells in ETO groups. Immunohistochemistry and electrophoresis of the P2X7 receptor were found in ETO groups. The mRNA levels of IBA1 are upregulated in the 0.7-mm ETO group, while immunohistochemistry showed higher IBA1+ -immunoreactive cells in both ETO groups. The expression of CD68 by electrophoresis and immunohistochemistry was observed in the ETO groups. For last, ELISA revealed increased levels of IL-6, IL-12, and CCL2 in the TG of ETO groups. Furthermore, the mRNA expression revealed augmented transcription factors and cytokines associated with lymphocyte activation, such as RORγt, IL-17, Tbet, IFNγ, FOXP3, and IL-10. The findings of this study suggested that ETO activates SGCs in TG, and purinergic signaling and CX3CL1/CX3CR1 axis were upregulated. We uncovered the involvement of a distinct subtype of macrophages, named sensory neuron-associated macrophage activation (sNMAs), and detected an expanded number of infiltrated macrophages onto TG. These findings indicate that ETO induces chronic/persistent immune response.

Parkinson's Disease-related Pains are Not Equal: Clinical, Somatosensory and Cortical Excitability Findings in Individuals With Nociceptive Pain.

Chronic pain is a frequent and burdensome nonmotor symptom of Parkinson's disease (PD). PD-related chronic pain can be classified as nociceptive, neuropathic, or nociplastic, the former being the most frequent subtype. However, differences in neurophysiologic profiles between these pain subtypes, and their potential prognostic and therapeutic implications have not been explored yet. This is a cross-sectional study on patients with PD (PwP)-related chronic pain (ie, started with or was aggravated by PD). Subjects were assessed for clinical and pain characteristics through questionnaires and underwent quantitative sensory tests and motor corticospinal excitability (CE) evaluations. Data were then compared between individuals with nociceptive and non-nociceptive (ie, neuropathic or nociplastic) pains. Thirty-five patients were included (51.4% male, 55.7 ± 11.0 years old), 20 of which had nociceptive pain. Patients with nociceptive PD-related pain had lower warm detection threshold (WDT, 33.34 ± 1.39 vs 34.34 ± 1.72, P = .019) and mechanical detection threshold (MDT, 2.55 ± 1.54 vs 3.86 ± .97, P = .007) compared to those with non-nociceptive pains. They also presented a higher proportion of low rest motor threshold values than the non-nociceptive pain ones (64.7% vs 26.6%, P = .048). In non-nociceptive pain patients, there was a negative correlation between WDT and non-motor symptoms scores (r = -.612, P = .045) and a positive correlation between MDT and average pain intensity (r = .629, P = .038), along with neuropathic pain symptom scores (r = .604, P = .049). It is possible to conclude that PD-related chronic pain subtypes have distinctive somatosensory and CE profiles. These preliminary data may help better frame previous contradictory findings in PwP and may have implications for future trial designs aiming at developing individually-tailored therapies. PERSPECTIVE: This work showed that PwP-related nociceptive chronic pain may have distinctive somatosensory and CE profiles than those with non-nociceptive pain subtypes. These data may help shed light on previous contradictory findings in PwP and guide future trials aiming at developing individually-tailored management strategies.