Effect of aerobic exercise program on neuropathic pain and quality of life in person with paraplegia: study protocol for a randomized controlled trial.

BACKGROUND: Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited. METHODOLOGY: This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6 weeks. OUTCOME MEASURES: International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity. DISCUSSION: The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3 weeks mid-intervention and after 6 weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023.

HCN channels in the lateral habenula regulate pain and comorbid depressive-like behaviors in mice.

AIMS: Comorbid anxiodepressive-like symptoms (CADS) in chronic pain are closely related to the overactivation of the lateral habenula (LHb). Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels have been implicated to play a key role in regulating neuronal excitability. However, the role of HCN channels in the LHb during CADS has not yet been characterized. This study aimed to investigate the effect of HCN channels in the LHb on CADS during chronic pain. METHODS: After chronic neuropathic pain induction by spared nerve injury (SNI), mice underwent a sucrose preference test, forced swimming test, tail suspension test, open-field test, and elevated plus maze test to evaluate their anxiodepressive-like behaviors. Electrophysiological recordings, immunohistochemistry, Western blotting, pharmacological experiments, and virus knockdown strategies were used to investigate the underlying mechanisms. RESULTS: Evident anxiodepressive-like behaviors were observed 6w after the SNI surgery, accompanied by increased neuronal excitability, enhanced HCN channel function, and increased expression of HCN2 isoforms in the LHb. Either pharmacological inhibition or virus knockdown of HCN2 channels significantly reduced LHb neuronal excitability and ameliorated both pain and depressive-like behaviors. CONCLUSION: Our results indicated that the LHb neurons were hyperactive under CADS in chronic pain, and this hyperactivation possibly resulted from the enhanced function of HCN channels and up-regulation of HCN2 isoforms.

Factors Associated With Pain Catastrophizing in Patients With Chronic Neuropathic Pain: A Cross-Sectional Study.

BACKGROUND: Pain catastrophizing is a significant factor in the recovery of patients with chronic pain. This topic has not received the warranted attention in clinical practice, while the outcomes of pain interventions have been suboptimal. This study explores the current situation of pain catastrophizing in patients with chronic neuropathic pain, its influencing factors, and further analyzes the complex relationship between these factors. METHODS: A cross-sectional study design was used to select preoperative patients hospitalized in the pain and spine surgery departments of two tertiary hospitals in Shandong Province, China, between February and August 2022. The Pain Catastrophizing Scale, Toronto Alexithymia Scale, Connor-Davidson Resilience Scale-Short, Somatization Sub-Scale of Symptom Checklist 90, and a sociodemographic questionnaire were used to evaluate participants' pain catastrophizing, alexithymia, psychological resilience, somatization, and relevant sociodemographic variables, respectively. Descriptive statistics, correlation, univariate, and multivariate analyses were employed throughout this process. RESULTS: Pain catastrophizing in patients with chronic neuropathic pain was affected by pain severity, disease type, alexithymia, psychological resilience, and somatization (p < .05). The mediating effect values of psychological resilience and somatization between alexithymia and pain catastrophizing were both 0.05, with 95% confidence intervals of (0.02, 0.09) and (0.02, 0.07), respectively. CONCLUSIONS: Pain severity, disease type, alexithymia, psychological resilience, and somatization all had a significant effect on pain catastrophizing. Healthcare workers must provide timely and accurate assessments of patients' pain levels to help prevent the onset of pain catastrophizing. Adopting measures to improve alexithymia and somatization symptoms, and focusing on enhancing patients' psychological resilience can also help reduce the level of pain catastrophizing. Cognitive behavioral therapy may be an effective treatment method for pain catastrophizing.

After 4 years of survival, patients treated for an oral or oropharyngeal cancer have more neurosensorial disorders than chronic pain and a better quality of life.

PURPOSE: During follow-up, patients in remission after oral or oropharyngeal cancer are few to express pain, depression or anxiety, their chief complain are dry mouth and difficulties to chewing. The aim of the study is to estimate prevalence of pain, quality of life and their evolution over four years. METHODS: This prospective observational study included 21 patients between June and September 2017. Clinical examination, neurosensory examination and questionnaires (using visual analogic scale DN4, PCS-CF, HADS EORTC QLQ30 and H&N 35) were performed and a second time 4 years later. RESULTS: After 4 years, 17 patients could be reviewed. In 2017 as in 2021, two patients (11.8 %) experience neuropathic pain. In 2017, 14 (82.3 %) reported paresthesia or dysesthesia or hypo/anesthesia, none of them have provoked pain to a mechanical or thermal stimulus. In 2021, only 9 (53 %) still report those symptoms. Global analysis of the questionnaire QLQC30 reveals a significant increase quality of life of all 17 patients (p = 0.0003). For the two questionnaires QLQC30 and QLQ-H&N 35, dry mouth, sticky saliva, difficulties for eating and relation with food, are strong grievances which an absence of amelioration or a degradation. CONCLUSIONS: Neurosensory disturbance is a frequent symptom but pain concerns only 11.8 % of patients. Quality of life increase globally, yet difficulties concerning oral cavity functions endure. IMPLICATIONS FOR CANCER SURVIVORS: For remission patients, pain is an unfrequent situation unlike neurosensory disturbance. Support care improve life quality. In case of onset of pain, recurrence and osteoradionecrosis should be mentioned immediately.

Path Analysis Between Family Functioning and Mental Health in People With Neuropathic Pain: Roles of Pain Intensity, Self-Perceived Burden, Pain Catastrophizing, and Functional Status.

PURPOSE: This study aimed to explore the pathways between family functioning and mental health in people with neuropathic pain, as well as to discuss the mediating role of pain intensity, self-perceived burden, pain catastrophizing, and functional status. DESIGN: Cross-sectional design reported using the STROBE guidelines. METHODS: A total of 277 people with neuropathic pain completed face-to-face questionnaires to evaluate family functioning, pain intensity, pain catastrophizing, self-perceived burden, functional status, and mental health. Structural equation modeling (SEM) was constructed to analyze the pathways between these variables. RESULTS: The positive total effect between family functioning and mental health was significant and partially mediated by self-perceived burden, pain catastrophizing, and functional status. In addition, better family functioning was associated with higher pain intensity, which worsens self-perceived burden, pain catastrophizing, and functional status, masking 23.68% of the positive effects between family functioning and mental health. CONCLUSIONS: Better family functioning was associated with better mental health, as explained by reduced self-perceived burden, reduced pain catastrophizing, and improved functional status. However, this benefit may be partially masked by the relationship that better family functioning explains higher pain intensity. CLINICAL IMPLICATIONS: Nurses' comprehensive assessment and management of neuropathic pain from both the family and individual levels, such as family functioning, pain intensity, self-perceived burden, pain catastrophizing, and functional status, may be beneficial in promoting patients' mental health. In addition, it is necessary to identify why good family functioning is associated with higher pain intensity and intervene in this regard.

Evaluating Sensitization-associated, Neuropathic-like Symptoms and Psychological Factors in Patients With Interstitial Lung Disease.

The aims of this study were to phenotype pain in patients with interstitial lung disease (ILD) by investigating the association between sensitization-associated symptoms with quality of life, anxiety/depression, pain catastrophizing, and kinesiophobia levels and identifying those risk factors explaining the variance of quality of life in individuals with ILD and pain. One hundred and thirty-two (38.6% women, mean age: 70, standard deviation: 10.5 years) patients with ILD completed clinical (age, sex, height, weight), psychological (Hospital Anxiety and Depression Scale [HADS] and the Pittsburgh Sleep Quality Index), and health-related quality of life (EQ-5D-5L) variables, as well as the Central Sensitization Inventory (CSI), the Self-Report Leeds Assessment of Neuropathic Symptoms (S-LANSS), Pain Catastrophizing Scale, and Tampa Scale for Kinesiophobia (TSK-11) questionnaires. The prevalence of sensitization-associated symptomatology (CSI), neuropathic-like features (S-LANSS), anxiety symptoms, depressive symptoms, or poor sleep was 20.5%, 23.5%, 23.6%, 22.9%, or 51.6%. Significant associations between CSI, S-LANSS, HADS-A, HADS-D, Pain Catastrophizing Scale, TSK-11, and EQ-5D-5L (.220 < r < .716) were found. The regression analysis revealed that CSI, TSK-11, and HADS-D explained 44.8% of the variance of EQ-5D-5L (r2 adjusted: .448). This study found the presence of sensitization-associated and neuropathic-like symptoms as well as other central nervous system-derived symptoms, such as anxiety, depression, poor sleep, pain catastrophizing, and kinesiophobia in 25% of ILD patients with pain. Sensitization-associated symptoms, depression, and kinesiophobia were associated with a worse quality of life. These findings would support that individuals with ILD can exhibit different pain phenotypes, including nociplastic-like pain phenotype based on self-reported measurements. PERSPECTIVE: Pain in patients with ILD can fulfill features of different phenotypes, including nociplastic pain, when sensory, emotional, and cognitive mechanisms are involved at the same time.

Associations of long-term clinical recovery and improved quality of life across ICD-11 chronic pain categories in a real-world registry study.

BACKGROUND: There is little knowledge of what factors are needed for successful chronic pain management. We aim to identify psychosocial and treatment predictors of clinical recovery and improved quality of life (QOL) at 12-month follow-up across three chronic pain groups, based on the International Classification of Diseases-11: neuropathic pain, secondary non-neuropathic pain, and primary pain. Furthermore, we investigate baseline differences across diagnostic groups. METHODS: The sample included baseline and 12-month follow-up data from 1056 chronic pain patients from the Oslo University Hospital's Pain Registry. Logistic regression models investigated longitudinal associations between psychosocial and treatment characteristics, and the outcome measures clinical recovery and improved QOL. Characteristics were compared across the diagnostic groups. RESULTS: Increased odds of clinical recovery and improved QOL were seen in patients receiving invasive treatment (OR = 8.04, 95% CI = 3.50-19.40; OR = 5.47, 95% CI = 2.42-12.86), while decreased odds of clinical recovery were seen for secondary non-neuropathic pain patients with pain-related disability (0.05, 95% CI = 0.01-0.29). In comparing baseline characteristics, neuropathic pain patients had lower QOL, and more severe insomnia compared to the other groups. CONCLUSION: Invasive treatment modalities were strongly associated with clinical recovery and improved QOL. Although this could be due to patient selection, it does warrant further examination as an intervention alternative for chronic pain. Intervention efficacy, risk factors and predictors of clinical recovery across diagnostic groups should be further investigated through longitudinal RCTs. SIGNIFICANCE: This observational study indicates a potential advantage in sustained recovery for pre-selected individuals with chronic pain who undergo invasive treatments. The relationship between sustained recovery and psychosocial factors differs across neuropathic, secondary non-neuropathic, and primary pain patients. This suggests that employing ICD-11 for classifying patients into mechanistically distinct pain groups could inform the evaluation and management of chronic pain. Furthermore, factors previously identified as negative indicators for long-term outcomes in chronic pain cohorts were not clinically significant in this study.

Psychologically based interventions for adults with chronic neuropathic pain: a scoping review.

OBJECTIVE: As psychologically based interventions have been shown to have clinical utility for adults with chronic pain generally, a similar benefit might be expected in the management of chronic neuropathic pain (NeuP). However, to date, this has not been established, with existing systematic reviews on this topic being hampered by the scarcity of randomized controlled trials (RCTs). This review aimed to identify the type of psychologically based interventions studied for adults with chronic NeuP. It also aimed to assess whether there are enough RCTs to justify undertaking an updated systematic review. METHODS: Seven databases and 2 clinical trial registries were searched for NeuP and psychologically based interventions from database inception to December 2021, and the search was updated in February 2023. The search was broadened by reviewing the reference list of included studies and contacting field experts. Predetermined study characteristics were extracted. RESULTS: Of 4682 records screened, 33 articles (less than 1%) met the eligibility criteria. Four broad intervention approaches were observed, including cognitive-behavioral approaches (n = 16), mindfulness/meditation (n = 10), trauma-focused therapy (n = 4), and hypnosis (n = 3). Thirteen RCTs were identified, and of these, 9 retained 20 participants in each arm after treatment. CONCLUSIONS: Cognitive-behavioral therapy was the most common therapeutic approach identified, whereas mindfulness/meditation was the most frequently used technique. Almost half to two-thirds of the studies reported significant improvements in pain, disability, or distress, which suggests that psychologically based interventions are potentially beneficial for adults with chronic NeuP. An updated systematic review seems warranted. STUDY REGISTRATION: Open Science Framework (https://osf.io) (December 6, 2021; DOI: 10.17605/OSF.IO/WNSTM).

Pain intensity and self-perceived burden mediate the relationship between family functioning and pain catastrophizing in patients with neuropathic pain.

This cross-sectional study aimed to investigate the relationship between family functioning, pain intensity, self-perceived burden, and pain catastrophizing. Moreover, we also wanted to explore the multiple mediating roles of pain intensity and self-perceived burden. From October 2022 to March 2023, 252 Chinese people with neuropathic pain completed face-to-face questionnaires to assess family functioning, pain intensity, self-perceived burden, and pain catastrophizing. Data analysis was done using descriptive statistics and a structural equation model. The results showed better family functioning was significantly associated with more intense pain, less self-perceived burden, and less pain catastrophizing. Mediation analysis showed that family functioning could indirectly affect pain catastrophizing through pain intensity and self-perceived burden in addition to a direct effect on pain catastrophizing. Moreover, the mediating variable of pain intensity played a masking role. These findings suggest that good family functioning can effectively reduce the self-perceived burden and pain catastrophizing in patients with neuropathic pain. However, family functioning cannot show its maximum effectiveness, and it may be necessary to construct a model of family functioning suitable for patients with neuropathic pain in the future.

Neuropathic Pain Affects Quality of Life in Breast Cancer Survivors with Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Despite the significant impact of chemotherapy-induced peripheral neuropathy on the quality of life for breast cancer survivors, there is a notable lack of comprehensive research. Therefore, a crucial need exists for further systematic investigation and inquiry into this matter. AIMS: This study examined predictors of quality of life in breast cancer survivors with chemotherapy-induced peripheral neuropathy. DESIGN: A cross-sectional, correlational design. SETTINGS: This study was conducted at a medical center in northern Taiwan and a teaching hospital in northeastern Taiwan. PARTICIPANTS/SUBJECTS: One hundred and thirty adult women with breast cancer, who have undergone chemotherapy and obtained a Total Neuropathy Scale-Clinical Version score>0, were enrolled. METHODS: Neuropathic pain, sleep disturbances, depression, and quality of life were evaluated using multiple regression analysis to identify quality of life predictors. Clinical importance was established using the minimally important difference of Functional Assessment of Cancer Therapy-Breast. RESULTS: The study indicated that improving depression (B = -10.87, p < .001) and neuropathic pain (B = -8.33, p = .004) may enhance the quality of life of breast cancer survivors with chemotherapy-induced peripheral neuropathy. Moreover, the individual's marital status and family history of breast cancer were identified as predictive factors. CONCLUSIONS: This study illuminates quality of life determinants for breast cancer survivors with chemotherapy-induced peripheral neuropathy, advocating comprehensive care and addressing depression and neuropathic pain for better outcomes.

Development of a pain self-management intervention framework for people with spinal cord injury.

BACKGROUND:  Pain is the most common reason for medical visits to primary health care practitioners. Pain self-management interventions are encouraged and there is no known self-management intervention framework available that clinicians and people with spinal cord injury (PWSCI) can use to guide treatment selection. AIM:  This study aimed to develop a pain self-management intervention framework for PWSCI. SETTING:  Online and facilitated in Gauteng, South Africa. METHODS:  A three-round modified e-Delphi method was used to reach an 80% consensus among a 21-expert panel. Fifty-nine interventions were distributed via REDCap and a final online audio meeting was held to either include or exclude interventions in the final framework. SPSS v27 was used to analyse descriptive data and content analysis was used for qualitative responses. RESULTS:  The final developed pain self-management framework consists of 56 interventions and includes interventions from multiple health professions to encompass medical, psychological, therapeutic and social interventions. Interventions are also specified for nociceptive and/or neuropathic pain and grouped according to the biopsychosocial model. CONCLUSION:  The interprofessional framework may be used as a guideline for PWSCI to alleviate pain, as well as assist health professionals in clinical decision-making, by providing them with the freedom to choose acceptable and adequate interventions that may be appropriate to treat the affected individual's pain.Contribution: Pain management is a basic need at the primary healthcare level and PWSCI need access to the broad range of interventions available to manage their pain. The framework highlights the variety of appropriate interventions to guide both health professionals and PWSCI with pain relief options.

Mitochondrial dysfunction and type I interferon signaling induce anxiodepressive-like behaviors in mice with neuropathic pain.

Clinical evidence indicates that major depression is a common comorbidity of chronic pain, including neuropathic pain; however, the cellular basis for chronic pain-mediated major depression remains unclear. Mitochondrial dysfunction induces neuroinflammation and has been implicated in various neurological diseases, including depression. Nevertheless, the relationship between mitochondrial dysfunction and anxiodepressive-like behaviors in the neuropathic pain state remains unclear. The current study examined whether hippocampal mitochondrial dysfunction and downstream neuroinflammation are involved in anxiodepressive-like behaviors in mice with neuropathic pain, which was induced by partial sciatic nerve ligation (PSNL). At 8 weeks after surgery, there was decreased levels of mitochondrial damage-associated molecular patterns, such as cytochrome c and mitochondrial transcription factor A, and increased level of cytosolic mitochondrial DNA in the contralateral hippocampus, suggesting the development of mitochondrial dysfunction. Type I interferon (IFN) mRNA expression in the hippocampus was also increased at 8 weeks after PSNL surgery. The restoration of mitochondrial function by curcumin blocked the increased cytosolic mitochondrial DNA and type I IFN expression in PSNL mice and improved anxiodepressive-like behaviors. Blockade of type I IFN signaling by anti-IFN alpha/beta receptor 1 antibody also improved anxiodepressive-like behaviors in PSNL mice. Together, these findings suggest that neuropathic pain induces hippocampal mitochondrial dysfunction followed by neuroinflammation, which may contribute to anxiodepressive-behaviors in the neuropathic pain state. Improving mitochondrial dysfunction and inhibiting type I IFN signaling in the hippocampus might be a novel approach to reducing comorbidities associated with neuropathic pain, such as depression and anxiety.

Abnormal Spontaneous Discharges of Primary Sensory Neurons and Pain Behavior in a Rat Model of Vascular Dementia.

Patients with vascular dementia experience more pain than healthy elders, potentially due to the presence of central neuropathic pain. However, the mechanisms underlying neuropathic pain in vascular dementia remain poorly understood, and there is currently a lack of effective treatment available. In this study, a rat model of vascular dementia was induced by permanently occluding the common carotid arteries bilaterally (2-VO). The cognitive impairments in the 2-VO rats were evaluated using the Morris Water Maze test, while HE and LBF staining were employed to assess brain tissue lesions in the hippocampal, cerebral cortex, and white matter regions known to be associated with severe memory and learning deficits. Furthermore, pain-related behavioral tests, including mechanical and thermal stimuli assessments, were conducted, and in vivo electrophysiological recordings of primary sensory neurons were performed. Compared to sham-operated and pre-operative rats, rats with vascular dementia exhibited mechanical allodynia and thermal hyperalgesia 30 days after surgery. Furthermore, in vivo electrophysiology revealed a significant increase in the occurrence of spontaneous activity of Aß- and C-fiber sensory neurons in the rat model of vascular dementia. These results indicate that neuropathic pain behaviors developed in the rat model of vascular dementia, and abnormal spontaneous discharges of primary sensory neurons may play a crucial role in the development of pain after vascular dementia.

Factors related to cognitive function in type-2 diabetes and neuropathic pain patients, the role of mood and sleep disorders in this relationship.

To compare cognitive function in patients with diabetes mellitus type-2 (T2DM) both with and without diabetic neuropathic pain (DNP). To analyse the relationship between mood and sleep disorders, quality of life and cognitive function in patients with DNP. Cross-sectional study conducted in patients with T2DM and neuropathy. The presence of DNP, cognitive function, mood status, sleep quality, health-related quality of life, pain intensity and phenotype of pain were measured. Descriptive, bivariate and multivariate analyses were performed. A total of 149 patients (71 with DNP) were included. Patients with and without DNP presented similar scores on the TYM (41.46; SD = 6.70 vs. 41.97; SD = 5.50) and those with DNP had a slightly higher frequency of cognitive impairment (TYM score ≤ 41: 40.8% vs. 43.6%). The patients without DNP performed better in the verbal fluency dimension (mean = 3.53; SD = 0.98 vs. mean = 3.82; SD = 0.66). Being older (B = - 0.258) and under treatment with insulin (B = - 2.919) were related with greater cognitive impairment. Obesity (OR = 17.277) and a longer duration of diabetes (OR = 1.317) were also related to greater risk of cognitive impairment. Impaired cognitive function in patients with DNP is more related to T2DM factors than pain factors. The presence of depression and a worse quality of life were related to a greater risk of cognitive impairment. Identifying and controlling these factors should be an essential intervention for maintaining the cognitive function in patients with T2DM and DNP.

Comprehensive Targeted Treatment for Neuropathic and Nociceptive Pain in Palliative Care Patients.

BACKGROUND: Pain is a common symptom in patients with advanced, metastatic, or terminal cancer. Neuropathic pain and psycho-emotional suffering are factors that increase the difficulty of pain management. Pain control in patients with cancer remains a challenge for medical professionals. STUDY QUESTION: What is the evolution of neuropathic/mixed pain compared with nociceptive pain under standardized treatment in patients with cancer? STUDY DESIGN: A prospective, longitudinal, open-label, nonrandomized study was conducted on patients with cancer pain. MEASURES AND OUTCOMES: Pain type was assessed at admission using the modified Brief Pain Inventory, and pain intensity was assessed daily using the Numerical Rating Scale for 14 days and on days 21 and 28. Screening of depression was performed on days 1, 7, 14, 21, and 28 using the Hamilton Depression Rating Scale. Patients with pain and depression received analgesics with antidepressants, while patients without depression received analgesics or analgesics with an anticonvulsant depending on the pain subtype. RESULTS: Of 72 patients, 23 had nociceptive pain and 49 had neuropathic/mixed pain. At admission, pain intensity was higher for patients with neuropathic/mixed pain compared with nociceptive pain (mean values: 7.06 vs. 5.82) with statistical significance ( P = 0.001) and remained as such at the end of this study (mean values: 3.77 vs. 2.73). A decrease in the mean pain intensity was observed in all types of pain, but without statistical significance regardless of pain type and treatment protocol used ( P = 0.77). If depression was present, antidepressants combined with analgesics decreased pain and depression scores significantly ( P = 0.001). CONCLUSIONS: Patients with neuropathic/mixed pain have higher levels of pain and lower response to treatment. Identifying psycho-emotional suffering can improve pain control by intervening in the physical and psycho-emotional components of pain.

Effects of rTMS and tDCS on neuropathic pain after brachial plexus injury: a randomized placebo-controlled pilot study.

Neuropathic pain after brachial plexus injury (NPBPI) is a highly disabling clinical condition and is increasingly prevalent due to increased motorcycle accidents. Currently, no randomized controlled trials have evaluated the effectiveness of non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS) in patients suffering from NPBPI. In this study, we directly compare the efficacy of 10-Hz rTMS and anodal 2 mA tDCS techniques applied over the motor cortex (5 daily consecutive sessions) in 20 patients with NPBPI, allocated into 2 parallel groups (active or sham). The order of the sessions was randomised for each of these treatment groups according to a crossover design and separated by a 30-day interval. Scores for "continuous" and "paroxysmal" pain (primary outcome) were tabulated after the last stimulation day and 30 days after. Secondary outcomes included the improvement in multidimensional aspects of pain, anxiety state and quality of life from a qualitative and quantitative approach. Active rTMS and tDCS were both superior to sham in reducing continuous (p < 0.001) and paroxysmal (p = 0.002; p = 0.02) pain as well as in multidimensional aspects of pain (p = 0.001; p = 0.002) and anxiety state (p = < 0.001; p = 0.005). Our results suggest rTMS and tDCS are able to treat NPBPI with little distinction in pain and anxiety state, which may promote the use of tDCS in brachial plexus injury pain management, as it constitutes an easier and more available technique.Clinical Trial Registration: http://www.ensaiosclinicos.gov.br/, RBR-5xnjbc - Sep 3, 2018.

The Evaluation of Pain with Nociceptive and Neuropathic Characteristics from Three Different Perspectives in Amyotrophic Lateral Sclerosis Patients: A Case Controlled Observational Study in Southwestern China.

Background: Pain was considered a common and neglected symptom in amyotrophic lateral sclerosis (ALS) and had a substantial impact on the quality of life of ALS patients and their caregivers. However, pain in ALS was mainly evaluated from the perspective of nociceptive pain; only three studies referred to neuropathic pain in ALS, and there has been yet no study considering the neuropathic pain characteristics in ALS patients from China. Therefore, the purpose of our study was to determine characteristics of pain (nociceptive pain and neuropathic pain) by three different types of questionnaires. The correlation between pain and clinical parameters in ALS patients was also evaluated. Methods: Patients were eligible if they fulfilled the criteria of probable and definitive ALS according to the revised El Escorial criteria. Healthy normal controls, matched to ALS patients by age and gender, were recruited. Pain was evaluated by numerical pain rating scale (NRS), Brief Pain Inventory (BPI), and Douleur Neuropathique-4 (DN4) in ALS patients and controls. Physical status of ALS patients was evaluated with ALS Functional Rating Scale-revised (ALSFRS-R). Results: 65 patients with sporadic ALS and 100 healthy normal controls in Southwestern China were included. Pain in the preceding week was more frequently reported by patients with ALS (30, 46.2%) than controls (36, 36%) (p = 0.193). DN4 score⩾4 was found in three ALS patients and one control (p = 0.480). Ten ALS patients (33.3%) and twenty-eight controls (77.8%) (p < 0.001) received therapy for pain. ALS patients with a DN4 score ≥ 4 had a longer disease duration and a higher PSI and PII score than ALS cases reporting nociceptive pain (p = 0.041, 0.048, and 0.027, respectively). Pain mainly interfered with ALS patients' mood, enjoyment of life, and the Pain Interference Index (PII) score. Conclusions: Our findings indicated that pain in our ALS cohorts was insufficiently treated and interfered with patients' mood and enjoyment of life. Most notably, we found that ALS patients with a DN4 score⩾4 may have a longer disease duration and a higher PSI and PII score than ALS patients reporting nociceptive pain, which has never been reported, strongly deserving further validation.

Escalating morphine dosage fails to elicit conditioned analgesia in a preclinical chronic neuropathic pain model.

Many people with chronic pain escalate their opioid dosage to counteract tolerance effects. A treatment regimen consisting of placebos admixed with opioids has been suggested as a possible therapeutic option that could reduce the harm of long-term opioid use. However, the analgesic efficacy of such a regimen requires further investigation before widespread adoption. We have recently reported that a 4-day pharmacological conditioning procedure, which paired morphine (6 mg/kg) with contextual cues, elicited placebo analgesia in subpopulations of male (35%) and female (25%) rats with sciatic nerve chronic constriction injury (CCI). Here, we investigated how an escalating morphine dosage during conditioning affects the incidence and strength of placebo analgesia. Forty-four male, Sprague-Dawley rats received CCI. Thirty-eight (86%) rats developed strong cold allodynia by day 6 post-surgery, as measured by hind paw withdrawal (HPW) behaviour on a 5°C cold plate (120 s). In this experiment, pharmacological conditioning consisted of an escalating morphine dose over 4 days (8/9/10/12 mg/kg). This dosing regimen produced strong reductions in HPW behaviour and counteracted the effects of morphine tolerance during conditioning. However, none of the rats given the placebo treatment (n = 12) demonstrated reductions in HPW behaviour when morphine was substituted for saline (i.e. placebo analgesia), but instead showed a strong behavioural response (rearing). These results demonstrate that a high, escalating dose of morphine failed to produce conditioned placebo analgesia in rats with CCI. It is possible that admixing placebos with opioids may be similarly ineffective in chronic pain patients when the opioids regimen is high or escalating.

Can dogs and cats really help our spinal cord stimulation patients?

OBJECTIVES: Pet ownership has been shown to decrease morbidity and mortality in several aspects of health but has not been studied in chronic pain patients. We evaluate whether subjects who underwent spinal cord stimulation (SCS) and own a pet have improved outcomes compared to non-pet owners. METHODS: After obtaining IRB approval, we re-contacted 38 subjects who underwent SCS surgery with preoperative and 1-year postoperative data on Numerical Rating Scale (NRS), McGill Pain Questionnaire (MPQ), Oswestry Disability Index (ODI), Beck Depression Inventory (BDI), and Pain Catastrophizing scale (PCS). We examined influence of pets and pet ownership-specific behaviors on improvement in SCS outcomes. RESULTS: Patients included 24 males/14 females with a mean age of 59.9 ± 11.5 years. At mean follow-up of 12.2 months (range 10-14), there were improvements in NRS, ODI, BDI, PCS and MPQ. Twenty subjects owned pets and 18 did not; all believed pet ownership could improve health. Pet owners improved more on NRS-right now (p = 0.05) and BDI (p = 0.05), and were more satisfied with SCS (p = 0.04). No significant improvement was seen in ODI, MPQ, or PCS. However, PCS did improve in pet owners who exercised their pet (PCS-total, p < 0.01; PCS-helplessness, p < 0.01; PCS-rumination, p = 0.05; PCS-magnification, p = 0.02). CONCLUSIONS: We provide preliminary evidence that pet ownership is associated with improved pain, depression and SCS satisfaction. Exercising with a pet also appears to be beneficial in limiting pain catastrophizing. Pets show promise as a novel means to improve patient SCS outcomes.