Effects of Botulinum Toxin-A for Spasticity and Nociceptive Pain in Individuals with Spinal Cord Injury: A Systematic Review and Meta-Analysis.

We conducted a systematic review and meta-analysis to examine the protective effects of botulinum toxin-A (Botox-A) on spasticity and nociceptive pain in individuals with spinal cord injuries (SCIs). PubMed, Embase, and Cochrane Library databases were searched from inception to July 2023. The primary outcome of interest was spasticity and nociceptive pain. We pooled the available data using the generic inverse variance method, and we used a fixed-effect/random-effects model. We then calculated standardized mean difference (SMD) and 95% confidence intervals (95% CIs) to estimate the effect size. A total of fourteen studies meeting the inclusion criteria comprised two randomized controlled trials, five pre-post studies, and seven case reports. Across the various study designs, the majority of trials were assessed to have fair to high quality. The meta-analysis shows that Botox-A significantly decreased spasticity (SMD, -1.73; 95% CI, -2.51 to -0.95; p<0.0001, I2=48%) and nociceptive pain (SMD, -1.79; 95% CI, -2.67 to -0.91; p<0.0001, I2=0%) in SCI patients. Furthermore, Botox-A intervention improved motor function, activities of daily living (ADL), and quality of life. Our study suggests that Botox-A may alleviate spasticity and nociceptive pain in SCI patients. Moreover, the observed improvements in motor function, ADL, and overall quality of life following Botox-A intervention underscore its pivotal role in enhancing patient outcomes.

Nociceptive Pain in Patients with Neuromuscular Disorders - A Cross-Sectional Clinical Study.

Background: Muscle pain is a common symptom in patients with neuromuscular disorders (NMD) and accounts for severely reduced quality of life. OBJECTIVE: This clinical study aimed to observe possible differences in pain prevalence among distinct NMDs and to determine whether the patients' nociceptive pain is influenced by gender, muscle strength and psychological factors and to examine potential pain-associated alterations in muscle properties. Methods: The cross-sectional study on nociceptive pain in various NMDs involved patient-reported outcomes, muscle strength evaluations (dynamometry and quick motor function test (QMFT)), nociceptive pain evaluations (muscular pressure pain threshold (PPT)), and non-invasive measurement of muscle stiffness, frequency, decrement, relaxation, and creep (myotonometry). Results: Involving 81 NMD patients and a control group, the study found high variability in pain prevalence among the subgroups. Patients with DM2 and FSHD had significantly higher levels of pain prevalence compared to other examined NMD subgroups and the control group. Female gender, high fatigue levels (representing factors such as depression, anxiety, stress, and impairment of quality of life), and low QMFT scores (representing reduced muscle strength) showed an association with increased sensitivity to pressure pain in the arm and leg region. As assessed by myotonometry, less pain is experienced in neck muscles with a high muscle tone, high stiffness, and a short relaxation time highlighting the importance of intrinsic muscular tone for their pressure pain sensitivity. Conclusion: Individualized therapeutic concepts including psychological and physical approaches in the pain management of patients with NMDs, especially in women, should be considered. Further research in this field is necessary to gain a more detailed insight into the perception of muscle pain.

Chronic nonspecific multiple-sites pain [CNMSP] of unknown etiology: Biopsychosocial method of evaluation for the primary care level.

Background: Understanding and dealing with chronic nonspecific pain (CNP) is the important entity at primary care hospital. Chronic nonspecific multiple-site pain [CNMSP] of unknown etiology creates diagnostic and therapeutic challenges for primary care physicians due to lack of guidance regarding evaluation and treatment. Aims and Objectives: To classify and formulate the evaluation, treatment strategies, and prediction of prognosis of patients with CNMSP of unknown etiology. Methods: Patients present with CNMSP of more than 3-month duration without any obvious medical cause. The biopsychosocial [BPS] model with 3P model was applied to see the biological, psychological, and social factors behind persistence. Finally, patients were classified into four groups for evaluation response to treatment and relapse rates in 12-month follow-up. Results: Of the total 243 patients of CNMSP, 243 [96.3%] were females. Sixty [24.7%] patients had short duration, and 183 [75.3%] had long duration. Headache was in 115 [47%], low back pain ± leg pain in 96 [39.4%], cervical pain ± shoulder/arm pain in 83 [34.1%], and diffuse body pain in 50 [20.5%] in various combinations. A total of 155 [63.8%] patients had high somatization-sensitization index (SSI), and 144 [59.3%] had low ferritin level. Group 1 [high SSI and low ferritin] had 37.9% of patients, group 2 [high SSI and normal ferritin] had 25.9% of patients, group 3 [low to medium SSI with low ferritin] had 21.4% of patients, and group 4 [low to medium SSI with normal ferritin] had 14.8% of patients. Response to pain symptoms was better in group 1, and relapse rate was higher in group 2. Conclusion: CNMSP of unknown etiology itself is a heterogeneous entity, and assessment based on the BPS model can be very useful to understand the treatment plan and outcome of these patients.

Phenotyping of chronic pain in breast cancer survivors: an original study using the cancer pain phenotyping (CANPPHE) Network multidisciplinary international guidelines.

PURPOSE: The primary aim of this cross-sectional study is to examine the prevalence of pain phenotypes in breast cancer survivors (BCS). A secondary aim entails examining whether health related quality of life differs between the main pain phenotypes in BCS. METHODS: BCS who experienced chronic pain were asked to complete the numeric pain rating scale for pain, Margolis pain diagram, and short form 36 (SF-36). Following administration of questionnaires and quantitative sensory examinations were applied. To determine the prevalence of the predominant type of pain, a recently proposed classification system by the Cancer Pain Phenotyping (CANPPHE) Network was used. RESULTS: Of the 86 female participants, 19 (22.09%) had dominant neuropathic pain, 18 (20.93%) had dominant nociceptive pain and 14 (16.28%) had dominant nociplastic pain. 35 participants (40.70%) were classified as having mixed pain. One-way ANOVA revealed a significant difference between the four pain groups for the SF-36 general health (F = 3.205, p = 0.027), social functioning (F = 4.093, p = 0.009), and pain (F = 3.603, p = 0.017) subscale scores. CONCLUSION: This study found that pain in BCS was mostly of mixed phenotype, followed by predominantly neuropathic and nociplastic pain. Furthermore, it was found that, compared to BCS with predominant neuropathic and nociceptive pain, BCS with predominant nociplastic pain have lower health related quality of life in the areas of bodily pain and social functioning.

Evaluation of the antinociceptive activities of natural propolis extract derived from stingless bee Trigona thoracica in mice.

Background: : Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. Methods: : The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. Results: : HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R2 = 0.999) and caffeic acid (R2 = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. Conclusions: : APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.

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.

Current understanding of nociplastic pain.

Nociplastic pain by the "International Association for the Study of Pain" is defined as pain that arises from altered nociception despite no clear evidence of nociceptive or neuropathic pain. Augmented central nervous system pain and sensory processing with altered pain modulation are suggested to be the mechanism of nociplastic pain. Clinical criteria for possible nociplastic pain affecting somatic structures include chronic regional pain and evoked pain hypersensitivity including allodynia with after-sensation. In addition to possible nociplastic pain, clinical criteria for probable nociplastic pain are pain hypersensitivity in the region of pain to non-noxious stimuli and presence of comorbidity such as generalized symptoms with sleep disturbance, fatigue, or cognitive problems with hypersensitivity of special senses. Criteria for definitive nociplastic pain is not determined yet. Eight specific disorders related to central sensitization are suggested to be restless leg syndrome, chronic fatigue syndrome, fibromyalgia, temporomandibular disorder, migraine or tension headache, irritable bowel syndrome, multiple chemical sensitivities, and whiplash injury; non-specific emotional disorders related to central sensitization include anxiety or panic attack and depression. These central sensitization pain syndromes are overlapped to previous functional pain syndromes which are unlike organic pain syndromes and have emotional components. Therefore, nociplastic pain can be understood as chronic altered nociception related to central sensitization including both sensory components with nociceptive and/or neuropathic pain and emotional components. Nociplastic pain may be developed to explain unexplained chronic pain beyond tissue damage or pathology regardless of its origin from nociceptive, neuropathic, emotional, or mixed pain components.

Pain types and risk factors in post-COVID-19.

Objectives: This study aims to accurately evaluate pain lasting longer than three months and falls under the category of chronic pain and to determine the risk factors to follow up and treat properly and to develop appropriate diagnostic and treatment algorithms. Patients and methods: Between March 2021 and December 2021, a total of 437 patients (162 males, 275 females; mean age: 44±14.6 years; range, 12 to 82 years) who were referred to the participating centers due to pain complaints and were diagnosed with post-COVID-19 condition according to the criteria defined by the World Health Organization (WHO) were included in the study. The patients were divided into three groups as nociceptive pain, neuropathic pain, and central sensitization, based on the physician's clinical evaluation and the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and Central Sensitization Inventory scores. Results: The most common diagnosis was nociceptive pain followed by central sensitization. Patients with nociceptive pain had less pain. It was found that not exercising regularly, having a chronic disease and being a woman were risk factors for central sensitization, having thyroid disease before COVID-19, and defining the current pain as very severe were risk factors for neuropathic pain. Conclusion: In the evaluation of post-COVID-19 pain, neuropathic pain and central sensitization should be also considered in addition to nociceptive pain and the severity of pain, systemic diseases and physical activity should be questioned.

Can we achieve pain stratification in musculoskeletal conditions? Implications for clinical practice.

In the last few years there has been an increased appreciation that pain perception in rheumatic and musculoskeletal diseases (RMDs) has several mechanisms which include nociceptive, inflammatory, nociplastic and neuropathic components. Studies in specific patient groups have also demonstrated that the pain experienced by people with specific diagnoses can present with distinctive components over time. For example, the pain observed in rheumatoid arthritis has been widely accepted to be caused by the activation of nociceptors, potentiated by the release of inflammatory mediators, including prostaglandins, leukotrienes and cytokine networks in the joint environment. However, people with RA may also experience nociplastic and neuropathic pain components, particularly when treatments with disease modifying anti-rheumatic drugs (DMARDs) have been implemented and are insufficient to control pain symptoms. In other RMDs, the concept of pain sensitisation or nociplastic pain in driving ongoing pain symptoms e.g. osteoarthritis and fibromyalgia, is becoming increasingly recognised. In this review, we explore the hypothesis that pain has distinct modalities based on clinical, pathophysiological, imaging and genetic factors. The concept of pain stratification in RMD is explored and implications for future management are also discussed.

Do we perceive sensations inside and outside of our body differently? Perceptual, emotional, and behavioral differences between visceral and somatic sensation, discomfort, and pain.

BACKGROUND: Experimental research evaluating differences between the visceral and somatic stimulation is limited to pain and typically uses different induction methods for visceral and somatic stimulation (e.g., rectal balloon distention vs. tactile hand stimulation). Our study aimed to compare differences in response time, intensity, unpleasantness, and threat between identical electrical visceral and somatic stimulations at both painful and non-painful perceptual thresholds. METHODS: Electrical stimulation was applied to the wrist and distal esophagus in 20 healthy participants. A double pseudorandom staircase determined perceptual thresholds of Sensation, Discomfort, and Pain for the somatic and visceral stimulations, separately. Stimulus reaction time (ms, via button press), and intensity, unpleasantness, and threat ratings were recorded after each stimulus. General linear mixed models compared differences in the four outcomes by stimulation type, threshold, and the stimulation type-by-threshold interaction. Sigmoidal maximum effect models evaluated differences in outcomes across all delivered stimulation intensities. KEY RESULTS: Overall, visceral stimulations were perceived as more intense, threatening, and unpleasant compared to somatic stimulations, but participants responded faster to somatic stimulations. There was no significant interaction effect, but planned contrasts demonstrated differences at individual thresholds. Across all delivered intensities, higher intensity stimulations were needed to reach the half-maximum effect of self-reported intensity, unpleasantness, and threat ratings in the visceral domain. CONCLUSIONS AND INFERENCES: Differences exist between modalities for both non-painful and painful sensations. These findings may have implications for translating paradigms and behavioral treatments from the somatic domain to the visceral domain, though future research in larger clinical samples is needed.

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.

Tetrahydrocannabinol and Cannabidiol for Pain Treatment-An Update on the Evidence.

In light of the current International Association for the Study of Pain (IASP) clinical practice guidelines (CPGs) and the European Society for Medical Oncology (ESMO) guidelines, the topic of cannabinoids in relation to pain remains controversial, with insufficient research presently available. Cannabinoids are an attractive pain management option due to their synergistic effects when administered with opioids, thereby also limiting the extent of respiratory depression. On their own, however, cannabinoids have been shown to have the potential to relieve specific subtypes of chronic pain in adults, although controversies remain. Among these subtypes are neuropathic, musculoskeletal, cancer, and geriatric pain. Another interesting feature is their effectiveness in chemotherapy-induced peripheral neuropathy (CIPN). Analgesic benefits are hypothesized to extend to HIV-associated neuropathic pain, as well as to lower back pain in the elderly. The aim of this article is to provide an up-to-date review of the existing preclinical as well as clinical studies, along with relevant systematic reviews addressing the roles of various types of cannabinoids in neuropathic pain settings. The impact of cannabinoids in chronic cancer pain and in non-cancer conditions, such as multiple sclerosis and headaches, are all discussed, as well as novel techniques of administration and relevant mechanisms of action.

Nociceptive pain assessed by the PainDETECT questionnaire may predict response to opioid treatment for chronic low back pain.

Introduction: The pharmacological management of chronic low back pain (LBP) is complex. The World Health Organisation recommends a laddered approach to pain medication usage. The PainDETECT questionnaire distinguishes between neuropathic pain (NeP), nociceptive pain (NoP), and ambiguous pain. By elucidating the difference in medication efficacy between these groups, clinicians can provide a tailored treatment plan to manage patient's pain. This study aimed to investigate the relationship between pharmacological treatments, pain categorizations, and medication efficacy as reported by patients. Methods: A secondary retrospective analysis of a prospectively collected database was conducted involving 318 consecutively recruited patients, aged 18 years and above, who completed PainDETECT, medication history and patient reported medication efficacy questionnaires. Medication history was categorized into four lines of treatment: first line (paracetamol ± non-prescribed anti-inflammatories), second line (prescribed anti-inflammatories), third line (anticonvulsants/neuromodulators) and fourth line (opioids). Medication efficacy was measured using a three-point Likert scale: effective (+2), somewhat effective (+1), no effect (0). Findings: The study included 120, 50, 54 and 94 patients on first line, second line, third line and fourth line treatment, respectively. The NeP group had higher mean numerical rating scale (NRS) compared to NoP group in all four lines of treatment (8.10 ± 1.59 vs. 5.47± 2.27, p < 0.001, 8.64± 1.43 vs. 5.52± 1.86, p < 0.001, 8.00± 1.07 vs. 6.37± 2.39, p < 0.01, and 8.05± 1.73 vs. 7.2± 1.29, p < 0.05). When confounding for severity of LBP as measured by NRS, the distribution of medication efficacy significantly differed amongst the NeP, ambiguous and NoP groups in patients undergoing fourth line pharmacological treatment (r2 = 8.623, p < 0.05). The NoP group exhibited significantly higher medication efficacy compared to the NeP group (U = 14.038, p < 0.05). There was no significant difference in medication efficacy across the pain classifications for first, second- and third-line treatment. Interpretation: Opioids was the only line of treatment more effective in targeting NoP, as determined by the PainDETECT questionnaire, compared to NeP. This pioneering study illustrates the complex nature of pharmacological management for chronic LBP. It underscores the importance of tailoring pharmacological treatment plans to fit individual pain profiles and expectations instead of adopting a blanket approach to pain management.

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.

Potential Role of Focal Microvibration (Equistasi®) in the Management of Chronic Pain: A Pilot Study.

INTRODUCTION: Chronic pain is one of the leading causes of medical consultation with a dramatic psychophysical and socioeconomic impact. Focal microvibration (Equistasi®) is a revolutionary technology that converts the thermal energy of the skin into vibration. Equistasi® was shown to be effective in the treatment of gait and balance dysfunction in many pathological conditions such as Parkinson's disease and multiple sclerosis. Our aim was to explore the efficacy of focal microvibration in the management of chronic pain. METHODS: We randomized 60 patients with pain of different origin into two groups: an experimental group (group E) treated with Equistasi, and a control group (group C) treated with standard pharmacological therapy. Pain, disability, and working capacity were evaluated by Brief Pain Inventory (BPI), Oswestry Disability Index (ODI), and Work Ability Index (WAI) at the baseline and after 7 (T7), 15 (T15), 30 (T30), 60 (T60), and 90 (T90) days. RESULTS: According to BPI, average and worst pain in the last 24 h significantly decreased in group E at T15 and this result persisted up to T90; pain interference on general activity, mood, waling ability, normal work, relations with other people, sleep, and enjoyment of life decreased in group E with a significant improvement from T15. Lifting activity and work ability in relation to demands also significantly improved in group E. No significant changes in BPI, ODI, and WAI scores were recorded in group C during the follow-up. CONCLUSIONS: Focal microvibration can be an effective tool for managing chronic pain in combination with other therapies.

Optogenetic Neuromodulation in Inflammatory Pain.

Inflammatory pain is one of the most prevalent forms of pain and negatively influences the quality of life. Neuromodulation has been an expanding field of pain medicine and is accepted by patients who have failed to respond to several conservative treatments. Despite its effectiveness, neuromodulation still lacks clinically robust evidence on inflammatory pain management. Optogenetics, which controls particular neurons or brain circuits with high spatiotemporal accuracy, has recently been an emerging area for inflammatory pain management and studying its mechanism. This review considers the fundamentals of optogenetics, including using opsins, targeting gene expression, and wavelength-specific light delivery techniques. The recent evidence on application and development of optogenetic neuromodulation in inflammatory pain is also summarised. The current limitations and challenges restricting the progression and clinical transformation of optogenetics in pain are addressed. Optogenetic neuromodulation in inflammatory pain has many potential targets, and developing strategies enabling clinical application is a desirable therapeutic approach and outcome.

Dor neuropática: sentimentos e vivências de pacientes após lesões traumáticas / Neuropathic pain: feelings and experiences of patients after traumatic injuries / Dolor neuropático: sentimientos y experiencias de pacientes después lesiones traumáticas

Objetivo: Compreender o cotidiano de portadores de dor neuropática decorrente de lesão traumática. Metodologia: Pesquisa exploratória, descritiva, de abordagem qualitativa, com participantes selecionados por meio de mídias sociais. A coleta de dados foi realizada entre o período de julho a setembro de 2022, com indivíduos adultos que possuem diagnóstico de dor neuropática após lesão traumática. A coleta ocorreu por meio de um formulário online, utilizando um questionário sociodemográfico e um questionário aberto, para a captura de informações pertinentes sobre seu caso clínico e vivência com a dor crônica. Os dados foram analisados por meio de Bardin. Todos os preceitos éticos foram respeitados e o projeto foi aprovado sob parecer n.º 5.529.581 da Universidade Cesumar. Resultados: Participaram 15 pessoas com dor neuropática, com prevalência do sexo feminino (93,3%), com idade entre 41 a 50 anos (66,7%). Observou-se que 53,3% relataram comorbidades crônicas, sendo as doenças psíquicas, ansiolíticas e cardíacas mais citadas. Ainda, 33,3% dos participantes relataram que foram internados por causas de dores ou por tentativa de suicídio, 93,3% usam opióides e analgésicos potentes e ainda foram citados antidepressivos e ansiolíticos em 62% das respostas. Dentre os temas em destaque nas respostas, sobressaíram-se "Contexto e diagnóstico da dor neuropática; Vivência e frequência da dor; Apoio profissional e familiar diante da doença". Considerações Finais: Nesse sentido, a percepção acerca dos profissionais de saúde e valorização do médico para o tratamento da dor neuropática está relacionada, muitas vezes, à necessidade de aumentar o conhecimento referente ao manejo da dor e à utilização de opióides.

Objective: To understand the daily life of patients with neuropathic pain resulting from traumatic injury. Methodology: Exploratory, descriptive research, with a qualitative approach, with participants selected through social media. Data collection was carried out between July and September 2022, with adult individuals diagnosed with neuropathic pain after traumatic injury. The collection took place through an online form, using a sociodemographic questionnaire and an open questionnaire, to capture relevant information about their clinical case and experience with chronic pain. Data were analyzed using Bardin. All ethical precepts were respected and the project was approved by report n.º 5,529,581 of Cesumar University. Results: 15 people with neuropathic pain participated, with a prevalence of females (93.3%), aged between 41 and 50 years (66.7%). It was observed that 53.3% reported chronic comorbidities, with psychic, anxiolytic and cardiac diseases being the most cited. Also, 33.3% of the participants reported that they were hospitalized due to pain or a suicide attempt, 93.3% used opioids and potent analgesics, and antidepressants and anxiolytics were mentioned in 62% of the answers. Among the topics highlighted in the responses, the most important were "Context and diagnosis of neuropathic pain; Experience and frequency of pain; Professional and family support in the face of the disease". Final Considerations: In this sense, the perception of health professionals and the appreciation of physicians for the treatment of neuropathic pain is often related to the need to increase knowledge regarding pain management and the use of opioids.

Objetivo: Comprender el cotidiano de los pacientes con dolor neuropático resultante de lesiones traumáticas. Metodología: Investigación exploratoria, descriptiva, con enfoque cualitativo, con participantes seleccionados a través de las redes sociales. La recolección de datos se llevó a cabo entre julio y septiembre de 2022, con individuos adultos diagnosticados con dolor neuropático posterior a una lesión traumática. La recogida se realizó a través de un formulario online, utilizando un cuestionario sociodemográfico y un cuestionario abierto, para captar información relevante sobre su caso clínico y experiencia con el dolor crónico. Los datos se analizaron utilizando Bardin. Se respetaron todos los preceptos éticos y el proyecto fue aprobado bajo el dictamen número 5.529.581 de la Universidad Cesumar. Resultados: Participaron 15 personas con dolor neuropático, con predominio del sexo femenino (93,3%), con edades entre 41 y 50 años (66,7%). Se observó que 53,3% relataron comorbilidades crónicas, siendo las enfermedades psíquicas, ansiolíticas y cardíacas las más citadas. Aún así, el 33,3% de los participantes informaron que fueron hospitalizados por dolor o intento de suicidio, el 93,3% usaba opioides y analgésicos potentes, y los antidepresivos y ansiolíticos se mencionaron en el 62% de las respuestas. Entre los temas destacados en las respuestas, los más importantes fueron "Contexto y diagnóstico del dolor neuropático; Experiencia y frecuencia del dolor; Apoyo profesional y familiar ante la enfermedad". Consideraciones Finales: En este sentido, la percepción de los profesionales de la salud y la apreciación de los médicos por el tratamiento del dolor neuropático muchas veces se relaciona con la necesidad de aumentar el conocimiento sobre el manejo del dolor y el uso de opioides.

A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain.

The transient receptor potential (TRP) superfamily of ion channels in humans comprises voltage-gated, non-selective cation channels expressed both in excitable as well as non-excitable cells. Four TRP channel subunits associate to create functional homo- or heterotetramers that allow the influx of calcium, sodium, and/or potassium. These channels are highly abundant in the brain and kidney and are important mediators of diverse biological functions including thermosensation, vascular tone, flow sensing in the kidney and irritant stimuli sensing. Inherited or acquired dysfunction of TRP channels influences cellular functions and signaling pathways resulting in multifaceted disorders affecting skeletal, renal, cardiovascular, and nervous systems. Studies have demonstrated the involvement of these channels in the generation and transduction of pain. Based on the multifaceted role orchestrated by these TRP channels, modulation of the activity of these channels presents an important strategy to influence cellular function by regulating intracellular calcium levels as well as membrane excitability. Therefore, there has been a remarkable pharmaceutical inclination toward TRP channels as therapeutic interventions. Several candidate drugs influencing the activity of these channels are already in the clinical trials pipeline. The present review encompasses the current understanding of TRP channels and TRP modulators in pain and pain management.

Restorative neurostimulation for chronic mechanical low back pain - Three year results from the United Kingdom post market clinical follow-up registry.

Introduction: Mechanical chronic low back pain is often associated with impaired neuromuscular control of the lumbar multifidus muscles, the most important stabilizers of the lumbar spine. Restorative neurostimulation is a modality for the treatment for this specific subset of patients aimed to facilitate restoration of neuromuscular control by bilateral stimulation of the L2 medial branches. Evidence from both prospective and randomised clinical trials to date has demonstrated substantial improvements in clinical outcomes such as pain, disability and health-related quality of life. Methods: This study is an open label prospective follow-up for the treatment of chronic mechanical low back pain of nociceptive origin with restorative neurostimulation. Patients completed assessments for pain, disability and health-related quality of life. Outcomes were collected at 45, 90 and 180 days, and 1, 2 and 3 years after the activation visit. Results: Forty-two patients were implanted with the device and 33 (79%) were available at the 3-year appointment. Patients in this cohort presented with severe chronic low back pain (NRS = 7.0 ± 0.2) and severe disability (ODI 46.6 ± 12.0). The health-related quality of life was also severely impacted at baseline (EQ-5D 0.426 ± 0.061). Changes in pain, disability and quality of life at three-year follow-up demonstrated a statistically significant improvement between baseline and 1, 2 and 3 years. After 3 years of therapy, average NRS scores had reduced to 2.7± 0.3 and mean ODI score to 26.0 ± 3.1 while EQ-5D-5L index improved to 0.707 ± 0.036. Conclusions: The ongoing follow-up of this post market cohort continues to demonstrate that restorative neurostimulation provides a statistically significant, clinically meaningful and durable response across pain, disability and quality-of life scores for patients suffering chronic mechanical low back pain that has been refractory to conventional management. Trial Registration: ClinicalTrials.gov Identifier: NCT01985230.

From CGRP to PACAP, VIP, and Beyond: Unraveling the Next Chapters in Migraine Treatment.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nonetheless, newly approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) have a 50% responder rate ranging from 27 to 71.0%, whereas CGRP receptor inhibitors have a 50% responder rate ranging from 56 to 71%. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge of PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.