Neuropathic Pain In Patients Research Articles

Neuropathic Pain Management, Pharmacological Approaches, Neuromodulation and Quality of Life

Neuropathic pain, which affects 7%–10% of the general population, is caused by a lesion or disease of the somatosensory system, which includes peripheral fibers and central neurons. There are numerous known causes of neuropathic pain, and as the world's population ages, the prevalence of diabetes mellitus rises, and cancer patients are more likely to survive postchemotherapy. Its occurrence is projected to rise. The intricacy of neuropathic symptoms, adverse outcomes, and challenging treatment choices all appear to contribute to the burden of chronic neuropathic pain. Crucially, neuropathic pain patients have a lower quality of life due to a higher need for prescription drugs, more frequent visits to the physician, the morbidity from the pain itself, and the underlying disease. The most effective strategy to treat neuropathic pain would employ the right combination of pharmacological and nonpharmacologic therapy. As first-line treatments, gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors are advised while tramadol and opioids are regarded as second-line therapy. Because there are currently insufficient high-quality trials, cannabinoids are advised as third-line treatments, and methadone and some anticonvulsants are suggested as fourth-line therapies. In cases of failure of pharmacological therapy or other special considerations, neuromodulation therapy is suggested, which involves deep brain stimulation, spinal cord stimulation, transcranial magnetic stimulation, and transcranial current stimulation and is broadly categorized under invasive and non-invasive neuromodulation procedures. In this study, we aim to comprehensively review the existing management strategies for neuropathic pain, specifically in the context of pharmacological, neuromodulation, and quality of life domains.

Nursing Management and Integrative/Integrated Applications in Diabetic Neuropathy

Diabetes is a chronic and systemic disease, characterized by hyperglycemia, with an increasing incidence and prevalence, which seriously affects the lives of individuals with acute and chronic complications. Endothelial damage and microvascular disorders occur as a result of inflammation and oxidative stress, with the increase of protein glycation, non-enzymatic glycation, and consequently the increase of end products in the tissues with hyperglycemia in diabetes. As a result of these events, peripheral and autonomic neuropathy develops in diabetic patients due to the demyelination of Schwann cells and decreased neuronal blood flow and nerve ischemia. Neuropathic pain patients due to diabetic peripheral neuropathy are seen in approximately 1/4 of the patients, and it negatively affects their quality of life. In the present study, nursing management and integrative practices in diabetic neuropathy, which is an important complication in diabetes, are discussed.

Involvement of TRPM7 Channel on the Induction of Diabetic Neuropathic Pain in Mice: Protective Role of Selenium and Curcumin.

Excessive levels of the mitochondrial reactive oxygen radical (mitSOX) and Ca2+ influx were found to cause neuropathic pain in patients with diabetes mellitus (DM). Naltriben (NLT) and mitSOX activate the transient receptor (TRP) melastatin 7 (TRPM7) channel, but antioxidants and carvacrol inhibit it. Selenium (Se) and curcumin (CRC) have been thoroughly studied for their modulator effects on streptozotocin (STZ)-induced neuropathic pain, apoptosis, and oxidative stress through the blockage of TRP channels in dorsal root ganglion (DRG) neurons. It has not yet been fully understood how Se and CRC protect against STZ-induced neuropathic pain by modulating TRPM7. Here, we assessed how Se and CRC affected the Ca2+ influx, mitSOX-mediated oxidative damage, and apoptosis in the DRGs of mice through modifying TRPM7 activity. Seven groups (control, Se, CRC, STZ, STZ + Se, STZ + CRC, and STZ + Se + CRC) were induced from the 56 male mice. We observed that the STZ-induced stimulation of TRPM7 increased mechanical neuropathic pain (von Frey), thermal neuropathic pain (hot plate), cytosolic Ca2+, TRPM7 current density, TRPM7 expression, lipid peroxidation, mitSOX, cytosolic ROS, apoptosis, caspase-3, caspase-8, and caspase-9 concentrations, whereas Se and CRC therapies diminished the alterations. The STZ-mediated decreases of DRG viability, brain glutathione, glutathione peroxidase, vitamin A, and vitamin E concentrations were also upregulated in the treatment groups by the therapies. These findings collectively imply that an imbalance of neuropathic pain, oxidative neurotoxicity, and apoptosis in the mice is caused by the STZ-mediated activation of TRPM7. However, the downregulation of TRPM7 activity caused by the injections of Se and CRC reduced the neurotoxicity and apoptosis.

Evaluation of (R)-[11C]PK11195 PET/MRI for Spinal Cord-Related Neuropathic Pain in Patients with Cervical Spinal Disorders

Activated microglia are involved in secondary injury after acute spinal cord injury (SCI) and in development of spinal cord-related neuropathic pain (NeP). The aim of the study was to assess expression of translocator protein 18 kDa (TSPO) as an indicator of microglial activation and to investigate visualization of the dynamics of activated microglia in the injured spinal cord using PET imaging with (R)-[11C]PK11195, a specific ligand for TSPO. In SCI chimeric animal models, TSPO was expressed mainly in activated microglia. Accumulation of (R)-[3H]PK11195 was confirmed in autoradiography and its dynamics in the injured spinal cord were visualized by (R)-[11C]PK11195 PET imaging in the acute phase after SCI. In clinical application of (R)-[11C]PK11195 PET/MRI of the cervical spinal cord in patients with NeP related to cervical disorders, uptake was found in cases up to 10 months after injury or surgery. No uptake could be visualized in the injured spinal cord in patients with chronic NeP at more than 1 year after injury or surgery, regardless of the degree of NeP. However, a positive correlation was found between standardized uptake value ratio and the severity of NeP, suggesting the potential of clinical application for objective evaluation of chronic NeP.

Relationship between the dose titration and adherence of mirogabalin in patients with peripheral neuropathic pain depending on renal function: a nationwide electronic medical record database study

ABSTRACT Background Mirogabalin has been attracting attention for treating peripheral neuropathic pain. The package insert recommends that mirogabalin should be titrated depending on renal function. Here, we investigated the relationship between dose titration patterns and adherence, and persistence of mirogabalin treatment. Research design and methods Peripheral neuropathic pain patients who initiated mirogabalin between March 2020 and May 2021 were identified using an electronic medical record database. The dose titration pattern was described according to degrees of renal function. Regression analyses were performed to compare adherence and persistence between the patients with and without titration. Results Of the 4,138 identified patients, 1,696 (41.0%) titrated the dose within 45 days and were more adherent than those without titration (Adjusted odds ratio: 1.75, 95% CI 1.21, 2.54). Of the total 952 patients with renal function parameters, 229 (24.1%) titrated to the effective dose within 45 days and were less likely to discontinue than those without titration (Adjusted hazard ratio: 0.57, 95% CI 0.40, 0.81). Conclusion Mirogabalin dose titration was associated with better adherence and persistence. It is important for mirogabalin treatment to determine the initial prescription dose based on renal function and subsequent dose titration according to the package insert. Trial registration UMIN000047313

Prognostic Factors for the Postoperative Improvement of Spinal Cord-Related Neuropathic Pain in Patients with Degenerative Cervical Myelopathy.

The number of patients with degenerative cervical myelopathy (DCM) requiring surgical treatment has markedly increased in today's aging society. Such patients often exhibit impaired activities of daily living because of motor dysfunction as well as neuropathic pain (NeP). Although many studies have demonstrated the safety and efficacy of surgical treatment for DCM, residual postoperative NeP has not been well described. Therefore, this study aimed to identify the predictors of postoperative NeP improvement in patients with DCM. This retrospective study included 92 outpatients with postoperative chronic NeP (≥3 months) related to DCM. Data were obtained from clinical information, magnetic resonance imaging (MRI) findings, and patient-based questionnaires using the Neuropathic Pain Symptom Inventory (NPSI) and the Brief Scale for Psychiatric Problems in Orthopaedic Patients. Univariate and multivariate analyses were performed for patients with NPSI improvement rates <30% and ≥30% to identify prognostic factors. Among 92 patients, 61 (66.3%) had residual NeP, with a low improvement rate even after surgery. The independent negative prognostic factors for NeP improvement after surgery were older age at operation (odds ratio (OR): 0.932), longer symptom duration before surgery (OR: 0.589), and higher preoperative NPSI score (OR: 0.932). The cut-off value of symptom duration before surgery for postoperative NeP improvement was 1 year. By contrast, the preoperative Japanese Orthopaedic Association score and MRI findings, including signal intensity change and the degree of spinal cord compression, were not associated with postoperative NeP improvement. Moreover, even in patients with an NPSI improvement rate ≥30%, the NPSI subscores for deep pain and paresthesia/dysesthesia remained high. Discrepancies between physician- and image-based assessments and patient-based assessments were identified as factors associated with improvement in postoperative NeP. Our findings are important for both spine surgeons and patients to manage patient expectations with respect to recovery during the postoperative course.

The Identification of Human Translational Biomarkers of Neuropathic Pain and Cross-Species Validation Using an Animal Model

Neuropathic pain is a common chronic condition, which remains poorly understood. Many patients receiving treatment continue to experience severe pain, due to limited diagnostic/treatment management programmes. The development of objective clinical diagnostic/treatment strategies requires identification of robust biomarkers of neuropathic pain. To this end, we looked to identify biomarkers of chronic neuropathic pain by assessing gene expression profiles in an animal model of neuropathic pain, and differential gene expression in patients to determine the potential translatability. We demonstrated cross-species validation of several genes including those identified through bioinformatic analysis by assessing their expression in blood samples from neuropathic pain patients, according to conservative assessments of significance measured using Bonferroni-corrected p-values. These include CASP5 (p = 0.00226), CASP8 (p = 0.00587), CASP9 (p = 2.09 × 10−9), FPR2 (p = 0.00278), SH3BGRL3 (p = 0.00633), and TMEM88 (p = 0.00038). A ROC analysis revealed several combinations of genes to show high levels of discriminatory power in the comparison of neuropathic pain patients and control participants, of which the combination SH3BGRL3, TMEM88, and CASP9 achieved the highest level (AUROC = 0.923). The CASP9 gene was found to be common in five combinations of three genes revealing the highest levels of discriminatory power. In contrast, the gene combination PLAC8, ROMO1, and A3GALT2 showed the highest levels of discriminatory power in the comparison of neuropathic pain and nociceptive pain (AUROC = 0.919), when patients were grouped by S-LANSS scores. Molecules that demonstrate an active role in neuropathic pain have the potential to be developed into a biological measure for objective diagnostic tests, or as novel drug targets for improved pain management.

The assessment of neuropathic pain in patients with prediabetes

AimsNeuropathic pain is associated with several clinical conditions, including anxiety, depression, sleep disorders, and decreased quality of life; however, less evaluated in prediabetes. This study aims to assess neuropathic pain through validated diagnostic tools in prediabetes. MethodsOne hundred and seventy-two patients with prediabetes and 170 controls were included in this cross-sectional study. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale and Douleur Neuropathique 4 Questions (DN4) were used to evaluate neuropathic pain. The Visual Analog Scale (VAS) was used to estimate pain intensity. ResultsTwenty-three (13.4%) and 12 (7%) patients with prediabetes were diagnosed with neuropathic pain using DN4 and LANSS questionnaires, respectively. Neuropathic pain rates of the patients were higher than controls with two pain scales (p < 0.001). VAS scores were higher in prediabetes group than in controls (p = 0.021). LANSS, DN4, and VAS scores were positively correlated with HbA1c level (r = 0.184, p = 0.016; r = 0.180, p = 0.018; r = 0.188, p = 0.014, respectively). LANNS and DN4 scores were higher in female patients than in males (p < 0.001). ConclusionsNeuropathic pain was increased in prediabetes by DN4 and LANNS questionnaires. An appropriate diagnosis of neuropathic pain in prediabetes may prevent patients from different pain-related clinical conditions.

Neuropathic pain in peroneal nerve entrapment at the fibular head.

Peroneal neuropathy at the fibular head (PNFH) is a mononeuropathy that typically presents with drop foot and sensory abnormalities over the skin area innervated by the peroneal nerve. The aim of the present study was to evaluate neuropathic pain in patients with PNFH. Patients with clinical and electrodiagnostic features consistent with PNFH associated with weight loss, leg postures, or prolonged sleep were included in the present retrospective cohort study. Nerve conduction studies were performed in the bilateral lower extremities of all patients. The Leeds assessment of neuropathic symptoms and signs scale (LANSS) was applied to all patients. Thirty-two PNFH patients (78% males) were included in the study. The LANSS score in the majority of patients was lower than 12. There was 1 patient with a LANSS score of 12. The electrodiagnostic features of 16 patients were compatible with axonal degeneration. The mean LANSS scores of PNFH patients with and without axonal degeneration were 4.3 ± 3.7 and 5.2 ± 2.9, respectively (p = 0.255). The present study showed that neuropathic pain is a rare symptom in patients with PNFH associated with weight loss, leg postures, or prolonged sleep.

Different Profiles of the Triad of Lysophosphatidylcholine, Lysophosphatidic Acid, and Autotaxin in Patients with Neuropathic Pain Diseases: a Preliminary Observational Study.

The mechanisms underlying neuropathic pain remain unclear. Lysophosphatidic acid (LPA) is a bioactive phospholipid derived mainly from lysophosphatidylcholine (LPC) by extracellular autotaxin (ATX), and has attracted attention as a candidate biomarker of neuropathic pain. We aimed to investigate the levels of LPA, LPC, and ATX in patients with lumbar spinal canal stenosis (LSCS) or other neuropathic pain diseases, and to distinguish the underlying mechanism of LSCS from other neuropathic pain conditions. Furthermore, the levels of phosphorylated neurofilament heavy chain (pNF-H), an objective surrogate marker of axonal damage, were also measured. Cerebrospinal fluid (CSF) samples were obtained from 56 patients with LSCS (n = 31) and various etiologies other than LSCS (n = 25). Patients with LSCS complained of pain intensity comparable to that of patients without LSCS. The LPA levels were significantly higher in patients with LSCS than in non-LSCS patients, while the ATX levels were significantly lower. However, the differences in LPC and pNF-H levels between the two patient groups were not significant. The LPA/LPC ratio was significantly higher in the LSCS group. Notably, the difference in LPA between the two groups diminished in the analysis of covariance (ANCOVA) with ATX as a covariate. Thus, it helped to reveal that LPA synthesis in patients with LSCS depends more efficiently on ATX than in non-LSCS neuropathic pain patients with other etiologies. Our findings further suggest that the triad of LPA, LPC, and ATX in LSCS may contribute to the development and maintenance of neuropathic pain in a manner different from non-LSCS neuropathic conditions.

Factors correlated with neuropathic pain in patients with neuromyelitis optica spectrum disorder

BackgroundNeuropathic pain in neuromyelitis optica spectrum disorder (NMOSD) is common but has always been overlooked. This study was conducted to explore factors correlated with neuropathic pain in NMOSD and to evaluate associations between pain and quality of life. MethodsIn this cross-sectional study, NMOSD patients were interviewed face-to-face. The Brief Pain Inventory, Douleur Neuropathique 4, and Neuropathic Pain Symptom Inventory scales were used to evaluate pain. Patients completed the Beck Depression Inventory-II and Social Functioning-36 tests to evaluate depression and quality of life. ResultsA total of 122 NMOSD patients were enrolled. Eighty-one (66.4%; 95% CI, 39.9% to 92.9%) had current pain, of which 35 (28.7%; 95% CI, 20.7% to 36.7%) had neuropathic pain. Forty-nine (40.2%; 95% CI, 31.5% to 48.9%) patients experienced depression, which was moderate to severe in 22 patients. Multinomial logistic regression showed that significantly more patients with neuropathic pain had depression than those with other pain (OR, 4.15; 95% CI, 1.40 to 12.35; P=0.010) or no pain (OR, 5.65; 95% CI, 1.74 to 18.18; P=0.004). Significantly more patients with neuropathic pain had initial spinal cord involvement than those in the no-pain group (OR, 15.78; 95% CI, 1.37 to 182.15; P=0.027). Quality of life was severely affected in NMOSD patients with neuropathic pain. Only 29.6% were treated with analgesics, and none were prescribed antidepressants. ConclusionDepression was correlated with neuropathic pain and was often overlooked. Initial spinal cord involvement might indicate a higher risk for neuropathic pain. Neuropathic pain in NMOSD patients requires scrutiny.

Can We Utilize PROMIS Neuropathic Pain Quality for Assessment of Neuropathic Heel Pain?

Category: Hindfoot; Other Introduction/Purpose: Heel pain is one of the most common presentations encountered by foot and ankle specialists. While most etiologies of heel pain such as plantar fasciitis are mechanical stress driven nociceptive pain, a combined neuropathic mechanism may contribute to worse outcomes and challenges in pain management for a subset of these patients. Diagnosis and management of neuropathic pain in foot and ankle patients remain challenging. Since neuropathic pain may play an important part in indicating surgery or counseling heel pain patients, we investigated the plausibility of utilizing the Patient-Reported Outcomes Measurement Information System (PROMIS) Neuropathic Pain Quality (PQN) as an initial screening tool to diagnose and monitor the clinical effects of treatment. Secondary outcomes were prevalence of neuropathic pain and associated risk factors. Methods: New patients presenting to a tertiary care academic institution with heel pain were prospectively recruited. PROMIS PQN t-scores were obtained from all patients to detect and determine the severity of NP. Patients were grouped into no neuropathic pain (NP), mild neuropathic pain (NP), and severe NP based on the initial PROMIS PQN t-scores. Pain Interference (PI), Physical Function (PF), and Self-Efficacy (SE) scores were assessed at baseline, 30, and 90-day follow-up timepoints. Other factors such as age, smoking, body mass index (BMI), low back/neck pain, anxiety, depression, and medications were analyzed for association with outcomes. Linear mixed modeling was utilized to assess the main effects of time and NP on PROMIS t-scores, and meaningful clinically important difference (MCID) was compared. Results: A total of 48 patients with mean age of 52.4+-12.5 years old were recruited at the initial visit. The cohort consisted of 35 (73%) female patients, 7 (15%) diabetics, 6 (13%) current smokers, 18 (38%) with low back/neck pain, 6 (13%) with anxiety, 15 (31%) with depression, and 9 (19%) had taken neuromodulator, such as gabapentin. When using the PROMIS PQN as the assessment tool, 33 patients (69%) had NP at baseline; 23 (48%) with mild, and 10 (21%) with severe NP. BMI was the only significant independent factor associated with NP (p = 0.011). Higher baseline NP was significantly associated with higher PQN (p&lt;0.001) and PI (p=0.005), and lower SE (p=0.04) across timepoints. Patients who were detected to have NP based on the PQN t-score had lower PF at baseline with significantly less improvement in PF (3 vs 9.9, p=0.035), and did not meet MCID (Figure 1). Conclusion: Prevalence of neuropathic pain in patients presenting with heel pain was high. Neuropathic pain at baseline was significantly associated with worse pain and self-efficacy over time, and less clinically meaningful improvements in function. The PROMIS PQN may serve as a valuable tool to identify and guide clinical treatment decision pathways for patients with neuropathic heel pain.

Can noninvasive Brain Stimulation Improve Pain and Depressive Symptoms in Patients With Neuropathic Pain? A Systematic Review and Meta-Analysis.

Noninvasive brain stimulations (NIBS) have been increasingly applied to the patients with neuropathic pain (NP), while the effectiveness of NIBS in the management of NP is still conflicting. To examine the effectiveness of NIBS on pain and depression symptoms of patients with NP. A comprehensive literature retrieval was performed on MEDLINE, Embase, PsycINFO, PEDro, and CENTRAL from the establishment of the databases to June 2021. Randomized controlled trials comparing NIBS with sham stimulation were included. A total of thirteen trials comprising 498 participants met the inclusion criteria. The pooled analysis found a significant effect on the improvement of pain scores at post-treatment, favoring NIBS over sham stimulation (SMD = -0.60; 95% CI: -1.00 to -0.20; P = 0.004). Subgroup analysis showed that only transcranial direct current stimulation (tDCS) (SMD = -0.38; 95% CI: -0.71 to -0.04; P = 0.030) and high-frequency repetitive transcranial magnetic stimulation (H-rTMS) (SMD = -0.95; 95% CI: -1.85 to -0.04; P = 0.040) had positive effects on pain reduction among all types of NIBS. The favorable effects of NIBS remained significant at follow-up visit (SMD = -0.51; 95% CI: -0.79 to -0.23; P = 0.000), while only H-rTMS was found in subgroup analyses to significantly improve pain scales of the patients (SMD = -0.54; 95% CI: -0.85 to -0.24; P = 0.000). Additionally, overall NIBS showed no beneficial effect over sham stimulation in reducing depression symptoms of NP patients either at post-treatment (SMD = -0.19; 95% CI: -0.39 to 0.01; P = 0.061) or at follow-up visit (SMD = -0.18; 95% CI: -0.45 to 0.10; P = 0.202). This meta-analysis revealed the analgesic effect of NIBS on patients with NP, while no beneficial effect was observed on reducing concomitant depression symptoms. The findings recommended the clinical application of NIBS in patients with NP.

Sensory testing might not be perfect- but it is the best biomarker for pain phenotypes we have right now.

Currently available treatments for neuropathic pain fail in roughly half of the patients- and it is impossible to predict which treatments will help patients. Stratification of neuropathic pain patients is needed, and sensory profiling has so far been the most promising approach: it has been shown to be responsive to treatment, linked to potential mechanisms, and, most importantly, predictive of treatment success. Despite a number of limitations, it is the currently most promising stratification tool and should be refined rather than disregarded.

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.

Effects of high-dose opioid analgesia on survival, pain relief, quality of life and adverse drug reactions in cancer and neuropathic pain patients: a retrospective cohort study in real-world clinical practice.

BackgroundPain is a common symptom among cancer patients and directly affects their prognosis. As the leading drug for pain management, opioids are widely prescribed. So it is necessary to get people a correct understanding and application of opioids. In order to examine whether the use of high-dose opioids might affect survival and quality of life, this retrospective cohort study was performed to explore the outcomes of patients receiving high-dose opioids for pain management in a first-class tertiary hospital in China.MethodsWe retrospectively searched medical records of inpatients and outpatients with pain who were treated with opioids in The First Affiliated Hospital, Zhejiang University School of Medicine from July to December 2021. Forty-three cases who were treated with high-dose opioids meeting inclusion criteria. Among these patients, 37 had cancer pain and 6 had neuropathic pain. All patients had regular follow-up when readmission until to April 7, 2022. Medical records of patients on high-dose opioids (equivalent to morphine ≥300 mg/d) was collected, including numerical rating scale (NRS), Karnofsky performance score (KPS), survival and adverse drug reactions (ADRs). Pain relief, quality of life, survival, and ADRs of patients after pain treatment were analyzed and evaluated.ResultsThe NRS score was significantly reduced and pain was relieved after high-dose opioid treatment. The before and after average NRS score of cancer pain was 5.2±1.6 vs. 2.2±1.1 points (P<0.001), neuropathic pain was 5.0±2.2 vs. 1.3±1.2 points (P<0.05), respectively. Although there is no statistical difference, quality of life showed a trend of improvement compared with before treatment. The before and after average KPS scores of cancer pain patients was 55.7±17.3 vs. 62.4±20.0, and neuropathic pain patients was 71.7±9.0 vs. 83.3±4.7. There were no intolerable ADRs. The median survival time was 238 days and 83 days in patients with cancer pain who received high-dose opioids and ultra-high dose opioids (equivalent to morphine ≥600 mg/d).ConclusionsMultimodal high-dose opioid pain treatments are important approaches to effectively relieve moderate to severe pain and improve the quality of life of patients. This study provides a clinical basis for future pain treatment with high-dose opioids.

Neuropathic Pain Component in Patients with Cervical Radicular Pain: A Single-Center Retrospective Study.

Background and Objectives: Evidence regarding the prevalence of neuropathic pain in patients with cervical radicular pain is limited. This study aimed to investigate the prevalence of neuropathic pain components in patients with cervical radicular pain using established screening tools and identify the relationship between neuropathic pain components and clinical factors. Materials and Methods: Data from 103 patients (aged ≥ 20 years) with cervical radicular pain who visited our pain clinic were analyzed retrospectively. Demographic characteristics, history of neck surgery, pain intensity using numeric rating score, dominant pain site, duration of symptoms, and neck disability index were assessed. The prevalence of neuropathic pain components was defined according to the Douleur Neuropathique 4 questions and painDETECT questionnaire tools. Patient characteristics were compared using the chi-square test or Fisher’s exact test for categorical variables and the independent t-test or Mann–Whitney U test for continuous variables. The correlation between neck disability index and other variables was analyzed using Pearson’s correlation coefficient. Results: Of the 103 patients, 29 (28.1%) had neuropathic pain components. The neck disability index was significantly higher (p < 0.001) for patients in the neuropathic pain group (23.79 ± 6.35) than that in the non- neuropathic pain group (18.43 ± 7.68). The Douleur Neuropathique 4 questions (r = 0.221, p < 0.025) and painDETECT questionnaire (r = 0.368, p < 0.001) scores positively correlated with the neck disability index score. Conclusions: The prevalence of neuropathic pain components in patients with cervical radicular pain was low. The patients in our study showed a strong correlation between functional deterioration and their neuropathic pain screening score. This study may be useful in understanding the characteristics of cervical radicular pain.

Is pregabalin better than gabapentin in treatment of neuropathic pain? An observation-based study at tertiary care centre of North India

Background: The present study was undertaken to assess the efficacy of pregabalin and gabapentin in treatment of neuropathic pain at a government tertiary care hospital of Uttar Pradesh, India. Due to indiscriminate use of drugs for treatment of neuropathic pain, selection of an effective drug is need of hour.Methods: Out of 130 patients, 62 patients were given pregabalin and 68 were given gabapentin. Douleur Neuropathique 4 questionnaire (DN4) which was used to diagnose patients of neuropathic pain. Efficacy of drug was based on their capability to decrease neuropathic pain at regular intervals.Results: On comparing the efficacy of drugs by their ability to decrease neuropathic pain, there was a significant difference when comparing pregabalin and gabapentin, pregabalin being statistically significant than gabapentin.Conclusions: On the basis present study efficacy of pregabalin 300 mg once daily brought better improvement of symptoms and sign than that of gabapentin 600 mg administered once daily dose. So pregabalin is a better drug than gabapentin.

The risk factors of neuropathic pain in neuromyelitis optica spectrum disorder: a retrospective case-cohort study

BackgroundNeuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain.ObjectiveTo investigate the risk factors of neuropathic pain in a NMOSD cohort.Materials and methodsOur study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”.ResultsOne hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions (≥ 3 spinal lesions), extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions (OR 20.21 [1.18–346.05], P = 0.038) and age (OR 1.35 (1–1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97–151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients.ConclusionExtended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.

Development of a variant of dinutuximab with enhanced antitumor efficacy and reduced induction of neuropathic pain.

Dinutuximab (ch14.18) was the first approved monoclonal antibody against the tumor‐associated antigen disialoganglioside GD2. Despite its success in treating neuroblastoma (NB), it triggers a significant amount of neuropathic pain in patients, possibly through complement‐dependent cytotoxicity (CDC). We hypothesized that modifying ch14.18 using antibody engineering techniques, such as humanization, affinity maturation, and Fc engineering, may enable the development of next‐generation GD2‐specific antibodies with reduced neuropathic pain and enhanced antitumor activity. In this study we developed the H3‐16 IgG1m4 antibody from ch14.18 IgG1. H3‐16 IgG1m4 exhibited enhanced binding activity to GD2 molecules and GD2‐positive cell lines as revealed by ELISA, and its cross‐binding activity to other gangliosides was not altered. The CDC activity of H3‐16 IgG1m4 was decreased, and the antibody‐dependent cellular cytotoxicity (ADCC) activity was enhanced. The pain response after H3‐16 IgG1m4 antibody administration was also reduced, as demonstrated using the von Frey test in Sprague–Dawley (SD) rats. In summary, H3‐16 IgG1m4 may have potential as a monoclonal antibody with reduced side effects.