Prognosis of Pain after Stroke during Rehabilitation Depends on the Pain Quality.

OBJECTIVE: Pain after a stroke interferes with daily life and the rehabilitation process. This study aimed to clarify the prognosis of pain in subgroups of patients with pain after a stroke using pain quality data. METHODS: The study included 85 patients with pain after stroke undergoing exercise-based rehabilitation. Items of the Neuropathic Pain Symptom Inventory (NPSI) were used, and patients with pain after stroke were clustered according to their scores of NPSI. Other clinical assessments, such as physical and psychological conditions, were assessed by interviews and questionnaires, and then these were compared among subgroups in a cross-sectional analysis. Longitudinal pain intensity in each subgroup was recorded during 12 weeks after the stroke and the patients' pain prognoses were compared between subgroups. RESULTS: Four distinct subgroups were clustered: cluster 1 (cold-evoked pain and tingling), cluster 2 (tingling only), cluster 3 (pressure-evoked pain), and cluster 4 (deep muscle pain with a squeezing and pressure sensation). The cross-sectional analysis showed varying clinical symptoms among the subgroups, with differences in the prevalence of joint pain, limited range of motion, somatosensory dysfunction, and allodynia. There were no significant differences in pain intensity at baseline among the subgroups. A longitudinal analysis showed divergent prognoses of pain intensity among the subgroups. The pain intensity in cluster 4 was significantly alleviated, which suggested that musculoskeletal pain could be reduced with conventional exercise-based rehabilitation. However, the pain intensity of patients in clusters 1 and 2 remained over 12 weeks. CONCLUSION: The study classified patients into clinically meaningful subgroups using pain quality data and provided insight into their prognosis of pain. The findings could be useful for guiding personalized rehabilitation strategies for pain management. IMPACT: Assessment of pain quality in patients with pain after stroke leads to personalized rehabilitation for pain management.

Development of an advanced liquid chromatography-tandem mass spectrometry measurement system for simultaneous sphingolipid analysis.

Mass spectrometry-based lipidomics approaches offer valuable tools for the detection and quantification of various lipid species, including sphingolipids. The present study aimed to develop a new method to simultaneously detect various sphingolipid species that applies to diverse biological samples. We developed and validated a measurement system by employing a single-column liquid chromatography-mass spectrometry system utilizing a normal-phase separation mode with positive ionization. The measurement system provided precision with a coefficient of variant below 20% for sphingolipids in all types of samples, and we observed good linearity in diluted serum samples. This system can measure the following sphingolipids: sphingosine 1-phosphate (S1P), sphingosine (Sph), dihydroS1P (dhS1P), dihydroSph (dhSph), ceramide 1-phosphate (Cer1P), hexosylceramide (HexCer), lactosylceramide (LacCer), dh-ceramide, deoxy-ceramide, deoxy-dh-ceramide, and sphingomyelin (SM). By measuring these sphingolipids in cell lysates where S1P lyase expression level was modulated, we could observe significant and dynamic modulations of sphingolipids in a comprehensive manner. Our newly established and validated measurement system can simultaneously measure many kinds of sphingolipids in biological samples. It holds great promise as a valuable tool for laboratory testing applications to detect overall modulations of sphingolipids, which have been proposed to be involved in pathogenesis processes in a series of elegant basic research studies.

Effectiveness of antipsychotics for managing agitated delirium in patients with advanced cancer: a secondary analysis of a multicenter prospective observational study in Japan (Phase-R).

PURPOSE: Delirium is a common and serious comorbidity in patients with advanced cancer, necessitating effective management. Nonetheless, effective drugs for managing agitated delirium in patients with advanced cancer remain unclear in real-world settings. Thus, the present study aimed to explore an effective pharmacotherapy for this condition. METHODS: We conducted a secondary analysis of a multicenter prospective observational study in Japan. The analysis included patients with advanced cancer who presented with agitated delirium and received pharmacotherapy. Agitation was defined as a score of the Richmond Agitation-Sedation Scale for palliative care (RASS-PAL) of ≥ 1. The outcome was defined as -2 ≤ RASS-PAL ≤ 0 at 72 h after the initiation of pharmacotherapy. Multiple propensity scores were quantified using a multinomial logistic regression model, and adjusted odds ratios (ORs) were calculated for haloperidol, chlorpromazine, olanzapine, quetiapine, and risperidone. RESULTS: The analysis included 271 patients with agitated delirium, and 87 (32%) showed -2 ≤ RASS-PAL ≤ 0 on day 3. The propensity score-adjusted OR of olanzapine was statistically significant (OR, 2.91; 95% confidence interval, 1.12 to 7.80; P = 0.030). CONCLUSIONS: The findings suggest that olanzapine may effectively improve delirium agitation in patients with advanced cancer.

Neuropathic pain development and maintenance and its association with motor recovery after cervical spinal cord injury.

BACKGROUND: In our published randomized controlled trial, we revealed that patients with acute ASIA Grade C incomplete cervical spinal cord injury (SCI) who underwent early surgery (within 24 h post-injury) had accelerated motor recovery at six months than those with delayed surgery (>2 weeks post-injury); however, neuropathic pain (NeP) worsened regardless of surgery timing. Here, we conducted post-hoc analyses to intensively assess NeP development and maintenance. METHODS: Of 44 patients (median 64.5 years; three female; early intervention, n = 26), NeP was categorized into at-level and below-level pain and evaluated at  two weeks and one year after injury using the Neuropathic Pain Symptom Inventory (NPSI). We compared the two groups based on background characteristics. A mixed-design analysis of variance with sex as a covariate was conducted to analyze motor recovery and Health-related quality of life (HRQOL) in groups with severe (NPSI ≥ 10) or mild (NPSI < 10) pain. RESULTS: Upper and lower limb motor impairments were comparable between both groups regardless of pain severity. Severe at-level pain remained stable and worsened at one year than mild at-level pain; however, the upper- and lower-limb motor scores and HRQOL had comparable recovery. Background characteristics did not affect severity or time course of NeP. Patients with severe below-level pain demonstrated slower lower-limb motor recovery than those with mild below-level pain, whereas HRQOL improved regardless of pain severity. CONCLUSIONS: Both at-level and below-level NeP developed and persisted relatively early in the course of traumatic SCI with incomplete motor paralysis; their severities worsened over time or remained severe since onset.

Secondary trigeminal neuralgia caused by lung adenocarcinoma metastasis on trigeminal nerve roots successfully relieved by opioids: A case report.

Secondary trigeminal neuralgia (TN) is caused by identifiable diseases or lesions of the trigeminal nerve root, Gasserian ganglion and/or pons. TN is a neuropathic pain disorder characterized by electric shock-like or stabbing pain in the facial region, which can lead to impaired health-related quality of life. The present case report describes a rare case of secondary TN caused by trigeminal nerve metastases from lung adenocarcinoma, in which opioids provided symptomatic relief. The patient was a 46-year-old man with stage IV lung adenocarcinoma. They were admitted to hospital for the introduction of fifth-line chemotherapy because of previous chemotherapy-refractory disease progression. Electric shock-like or stabbing pain in the left facial area and bilateral auditory disturbances coincided with intracranial peri-brainstem metastases. Facial pain was triggered by mastication, making it difficult for the patient to eat. A fentanyl transdermal patch (25 mcg/h) was initiated following a diagnosis of TN secondary to lung adenocarcinoma metastases on the trigeminal nerves by magnetic resonance imaging. Subsequently, the facial pain improved rapidly. In conclusion, unlike classic and idiopathic TN, which is usually treated with carbamazepine as a first-line drug, oncologic secondary TN can be treated with opioids.

Cerebrospinal Fluid Lysophosphatidylcholine Species for Distinguishing Narrowing of the Lumbar Spine.

BACKGROUND: Reoperation, sometimes multiple, is common with progressively worse outcomes in patients with degenerative lumbar spine diseases. Lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acid, in the cerebrospinal fluid (CSF) is a possible biomarker for neuropathic pain and discriminating neuropathic pain caused by lumbar spinal canal stenosis (LSCS) from other etiologies. This study aimed to explore this possible use of LPC species in the CSF. METHODS: Patients with LSCS (n = 137) and persistent spinal pain syndrome (n = 22) were subjected in this multi-site observational study. The CSF was collected by lumbar puncture. Using liquid chromatography-tandem mass spectrometry, we measured 6 LPC species, (16:0), (18:0), (18:1), (18:2), (20:4), and (22:6), in the CSF. We compared the LPC values between the groups and determined the cutoff levels that could efficiently discriminate the groups with high accuracy. RESULTS: The levels of all measured LPC species were significantly higher in the LSCS group than the persistent spinal pain syndrome group. Four LPC species demonstrated more than 0.80 area under the curve obtained from the receiver operating characteristic curve analysis. Although the specificity of cutoff levels for the 6 LPC species was low to moderate, their sensitivity was consistently high. CONCLUSIONS: The existing diagnostic protocols combining physical examinations and morphological imaging studies for lumbar spinal pain have limited sensitivity. Measuring LPC species in the CSF is a promising objective laboratory test and could be suitable for detecting the presence of lumbar spinal stenosis and can help indications for surgery.

Effect of experimentally induced plantar pain on trunk posture during gait.

[Purpose] Plantar pain is associated with the prevalence of low back pain. Therefore, it is reasonable to assume that some kind of physical change should be occurring in the trunk due to plantar pain. However, the physical effect of plantar pain on the trunk remains unknown. We evaluated the effect of plantar pain on trunk posture during gait. [Participants and Methods] Ten healthy volunteers participated in the present study. Participants walked under two conditions: without pain and with pain. In the with pain condition, we set pain-inducing devices to the right foot to induce plantar pain during stance phase. By using 3D motion analysis system, the angles of the head, thorax, and pelvis segments, as well as the neck, trunk, bilateral hip, bilateral knee, and bilateral ankle joints, were measured. We analyzed the angle data throughout the gait cycle by using one-dimensional statistical parametric mapping. [Results] The anterior trunk tilt was observed in the right stance phase. [Conclusion] The anterior trunk tilt observed in the with pain condition may be a burden on the trunk. Our results presented one of the possible reasons for increased prevalence of low back pain in the plantar pain patients.

Preliminary Efficacy, Feasibility, and Perceived Usefulness of a Smartphone-Based Self-Management System With Personalized Goal Setting and Feedback to Increase Step Count Among Workers With High Blood Pressure: Before-and-After Study.

BACKGROUND: High blood pressure (BP) and physical inactivity are the major risk factors for cardiovascular diseases. Mobile health is expected to support patients' self-management for improving cardiovascular health; the development of fully automated systems is necessary to minimize the workloads of health care providers. OBJECTIVE: The objective of our study was to evaluate the preliminary efficacy, feasibility, and perceived usefulness of an intervention using a novel smartphone-based self-management system (DialBetes Step) in increasing steps per day among workers with high BP. METHODS: On the basis of the Social Cognitive Theory, we developed personalized goal-setting and feedback functions and information delivery functions for increasing step count. Personalized goal setting and feedback consist of 4 components to support users' self-regulation and enhance their self-efficacy: goal setting for daily steps, positive feedback, action planning, and barrier identification and problem-solving. In the goal-setting component, users set their own step goals weekly in gradual increments based on the system's suggestion. We added these fully automated functions to an extant system with the function of self-monitoring daily step count, BP, body weight, blood glucose, exercise, and diet. We conducted a single-arm before-and-after study of workers with high BP who were willing to increase their physical activity. After an educational group session, participants used only the self-monitoring function for 2 weeks (baseline) and all functions of DialBetes Step for 24 weeks. We evaluated changes in steps per day, self-reported frequencies of self-regulation and self-management behavior, self-efficacy, and biomedical characteristics (home BP, BMI, visceral fat area, and glucose and lipid parameters) around week 6 (P1) of using the new functions and at the end of the intervention (P2). Participants rated the usefulness of the system using a paper-based questionnaire. RESULTS: We analyzed 30 participants (n=19, 63% male; mean age 52.9, SD 5.3 years); 1 (3%) participant dropped out of the intervention. The median percentage of step measurement was 97%. Compared with baseline (median 10,084 steps per day), steps per day significantly increased at P1 (median +1493 steps per day; P<.001), but the increase attenuated at P2 (median +1056 steps per day; P=.04). Frequencies of self-regulation and self-management behavior increased at P1 and P2. Goal-related self-efficacy tended to increase at P2 (median +5%; P=.05). Home BP substantially decreased only at P2. Of the other biomedical characteristics, BMI decreased significantly at P1 (P<.001) and P2 (P=.001), and high-density lipoprotein cholesterol increased significantly only at P1 (P<.001). DialBetes Step was rated as useful or moderately useful by 97% (28/29) of the participants. CONCLUSIONS: DialBetes Step intervention might be a feasible and useful way of increasing workers' step count for a short period and, consequently, improving their BP and BMI; self-efficacy-enhancing techniques of the system should be improved.

Adaptation and Limitations of painDETECT Questionnaire Score Approach Before and After Posterior Cervical Decompression Surgery.

BACKGROUND: The painDETECT questionnaire (PDQ) is one of the available screening tools for neuropathic pain (NeP), with a cut-off score of 13. This study aimed to investigate changes in PDQ scores in patients undergoing posterior cervical decompression surgery for degenerative cervical myelopathy (DCM). METHODS: Patients with DCM undergoing cervical laminoplasty or laminectomy with posterior fusion were recruited. They were asked to complete a booklet questionnaire including PDQ and Numerical Rating Scales (NRS) for pain at baseline and one year after surgery. Patients with a preoperative PDQ score ≥13 were further investigated. RESULTS: A total of 131 patients (mean age = 70.1 years; 77 male and 54 female) were analyzed. After posterior cervical decompression surgery for DCM, mean PDQ scores decreased from 8.93 to 7.28 (P = 0.008) in all patients. Of the 35 patients (27%) with preoperative PDQ scores ≥13, mean PDQ changed from 18.83 to 12.09 (P < 0.001). Comparing the NeP improved group (17 patients with postoperative PDQ scores ≤12) with the NeP residual group (18 patients with postoperative PDQ scores ≥13), the NeP improved group showed less preoperative neck pain (2.8 vs. 4.4, P = 0.043) compared to the NeP residual group. There was no difference in the postoperative satisfaction rate between the two groups. CONCLUSIONS: Approximately 30% of patients exhibited preoperative PDQ scores ≥13, and about half of these patients demonstrated improvements to below to the cut-off value for NeP after posterior cervical decompression surgery. The PDQ score change was relatively associated with preoperative neck pain.

Development of a Japanese Version of the Quality of Life at the End of Life-Cancer Scale.

CONTEXT: The Quality of Life at the End of Life-Cancer Scale (QUAL-EC) is a self-reported instrument to assesses the quality of life of patients with cancer near the end of life. OBJECTIVE: To test the reliability and validity of the QUAL-EC-J, a Japanese translated version of the QUAL-EC. METHODS: A total of 179 Japanese patients with advanced cancer completed the QUAL-EC-J, Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Rosenberg Self-Esteem Scale, Multidimensional Scale of Perceived Social Support, Functional Assessment of Cancer Therapy-General Scale, and Functional Assessment of Chronic Illness Therapy-Spiritual questionnaires. We performed confirmatory factor analysis of the four structures of the QUAL-EC and exploratory factor analysis of the QUAL-EC-J. Internal consistency was assessed using Cronbach's α coefficient and validity was examined by calculating correlations with relevant scales. RESULTS: Confirmatory factor analysis showed an inadequate fit to the original QUAL-EC structure. Exploratory factor analysis revealed a three-factor structure of the QUAL-EC-J, with Cronbach's α values of 0.68-0.88. All subscales were negatively correlated with depression and anxiety. Each subscale was correlated with related measures: "symptom control" with "physical well-being"; "acceptance of disease and life" with "social and family well-being" and "meaning/peace"; and "preparation for end of life" with "emotional well-being" and "meaning/peace." CONCLUSIONS: The QUAL-EC-J has a three-factor structure with acceptable reliability and sufficient validity. Differences in the factor structure between the QUAL-EC-J and the QUAL-EC may be due to cultural factors. Study findings suggest that utilization of the QUAL-EC-J could help to improve research and clinical care in advanced cancer in Japan.

Genetic Polymorphisms of ENPP2 Are Possibly Associated with Pain Severity and Opioid Dose Requirements in Patients with Inflammatory Pain Conditions: Clinical Observation Study.

Autotaxin, encoded by the ENPP2 gene, is a known key element of neuropathic pain; however, its involvement in nociceptive pain processing remains unclear. We explored the associations between postoperative pain intensity, 24-h postoperative opioid dose requirements, and 93 ENNP2-gene single-nucleotide polymorphisms (SNPs) in 362 healthy patients who underwent cosmetic surgery using the dominant, recessive, and genotypic models. Next, we validated the associations between relevant SNPs on the one hand and pain intensity and daily opioid dosages on the other in 89 patients with cancer-related pain. In this validation study, a Bonferroni correction for multiplicity was applied on all relevant SNPs of the ENPP2 gene and their respective models. In the exploratory study, three models of two SNPs (rs7832704 and rs2249015) were significantly associated with postoperative opioid doses, although the postoperative pain intensity was comparable. In the validation study, the three models of the two SNPs were also significantly associated with cancer pain intensity (p < 0.017). Patients with a minor allele homozygosity complained of more severe pain compared with patients with other genotypes when using comparable daily opioid doses. Our findings might suggest that autotaxin is associated with nociceptive pain processing and the regulation of opioid requirements.

Usefulness of lysophosphatidylcholine measurement in the cerebrospinal fluid for differential diagnosis of neuropathic pain: Possible introduction into clinical laboratory testing.

BACKGROUND: The differential diagnosis of neuropathic pain, especially discrimination between neuropathic pain caused by spinal canal stenosis (SCS) and neuropathic pain associated with causes other than SCS, is sometimes difficult; however, it is important for surgical application. METHODS: We established a reliable method for measuring lysophosphatidylcholine (LPC), a precursor of lysophosphatidic acids which are known as being pain initiators, using a liquid chromatography-tandem mass spectrometry method, and measured the LPC concentrations in the cerebrospinal fluid (CSF) in patients with SCS (SCS group; n = 76), patients with neuropathic pain caused by non-SCS diseases (Others group; n = 49), and control subjects without pain (control group; n = 92). RESULTS: Both within-run and between-run CV(%) were almost < 10 %, suggesting an enough performance for clinical introduction. The CSF concentrations of LPC (16:0) and LPC (18:0) were higher in the SCS group than those in the Control or Others group; the concentrations of LPC (18:1), LPC (18:2), LPC (20:4), LPC (22:6) levels were higher in the SCS group than those in the control or others group, but they were also higher in the Others group than those in the control group. The areas under the curve in the ROC curve analyses of LPC (18:1) for discriminating between the SCS and control groups, others and control groups, and SCS and others groups were 0.994, 0.860, and 0.869, respectively. CONCLUSIONS: LPC measurement in the CSF is useful for the differential diagnosis of neuropathic pain, especially for surgical decision-making, which is expected for clinical introduction.

Influence of vibrotactile random noise on the smoothness of the grasp movement in patients with chemotherapy-induced peripheral neuropathy.

Patients with chemotherapy-induced peripheral neuropathy (CIPN) often suffer from sensorimotor dysfunction of the distal portion of the extremities (e.g., loss of somatosensory sensation, numbness/tingling, difficulty typing on a keyboard, or difficulty buttoning/unbuttoning a shirt). The present study aimed to reveal the effects of subthreshold vibrotactile random noise stimulation on sensorimotor dysfunction in CIPN patients without exacerbating symptoms. Twenty-five patients with CIPN and 28 age-matched healthy adults participated in this study. To reveal the effects of subthreshold vibrotactile random noise stimulation on sensorimotor function, participants were asked to perform a tactile detection task and a grasp movement task during random noise stimulation delivered to the volar and dorsal wrist. We set three intensity conditions of the vibrotactile random noise: 0, 60, and 120% of the sensory threshold (Noise 0%, Noise 60%, and Noise 120% conditions). In the tactile detection task, a Semmes-Weinstein monofilament was applied to the volar surface of the tip of the index finger using standard testing measures. In the grasp movement task, the distance between the thumb and index finger was recorded while the participant attempted to grasp a target object, and the smoothness of the grasp movement was quantified by calculating normalized jerk in each experimental condition. The experimental data were compared using two-way repeated-measures analyses of variance with two factors: experimental condition (Noise 0, 60, 120%) × group (Healthy controls, CIPN patients). The tactile detection threshold and the smoothness of the grasp movement were only improved in the Noise 60% condition without exacerbating numbness/tingling in CIPN patients and healthy controls. The current study suggested that the development of treatment devices using stochastic resonance can improve sensorimotor function for CIPN patients.

Efficacy of treatments for pain and numbness in cancer survivors: a systematic review and meta-analysis.

BACKGROUND: Pain and numbness in cancer survivors frequently have negative impacts on quality of life (QoL). This meta-analysis aimed to identify the current treatment options for pain and numbness in cancer survivors and to evaluate their effects. METHODS: Cancer survivors were defined as patients diagnosed with cancer who had completed active cancer treatment, whose conditions were stable, and who had no evidence of recurrent or progressive disease. A systematic search through the PubMed, MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science, PsycInfo, and CINAHL databases was conducted, which targeted randomized controlled trials (RCTs) published until April 2022 that evaluated any type of treatment for pain or numbness in cancer survivors. A meta-analysis was conducted using the random-effects model to obtain the effect sizes of 7 types of treatments: opioid therapy, nonopioid pharmacotherapy, interventional therapy, acupuncture, education/cognitive behavioral therapy (CBT), physical exercise, and alternative medicine. RESULTS: A total of 36 studies involving 2,870 cancer survivors were included. Among them, 35 (n=2,813) were included in the meta-analysis for pain. The analysis suggested that physical exercise [n=761; 13 studies; standardized mean difference (SMD) -0.84; 95% confidence interval (CI): -1.14 to -0.55], acupuncture (n=409; 3 studies; SMD -0.80; 95% CI: -1.04 to -0.56), and alternative medicine (n=206; 6 studies; SMD -0.44; 95% CI: -0.71 to -0.16) could significantly reduce pain. Nonopioid pharmacotherapy and education/CBT did not demonstrate significant effects. No studies were identified that investigated the effects of opioid therapy or interventional therapy on pain. Regarding numbness, 5 studies (n=566) were included in the meta-analysis. Acupuncture (n=99; 2 studies) did not demonstrate significant effects on numbness, and the effects of nonopioid pharmacotherapy, education/CBT, and physical exercise could not be determined due to the small number of included studies. No studies were identified that investigated the effects of opioid therapy, interventional therapy, or alternative medicine on numbness. CONCLUSIONS: This meta-analysis suggested that physical exercise, acupuncture, and alternative medicine may reduce pain in cancer survivors, with a very small to moderate amount of evidence. The effect of treatments for numbness could not be determined due to the limited number of included studies. Further studies are needed, particularly on widely used pharmacotherapy.

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.

Background: Pain 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. Methods: We 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. Results: The 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). Conclusions: Multimodal 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.

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.

Elevation of serum plasminogen activator inhibitor-1 predicts postoperative delirium independent of neural damage: a sequential analysis.

Older adult surgical patients are susceptible to developing delirium. Early intervention can be initiated if a potential biomarker associated with delirium can be identified during the acute phase of surgery. Therefore, we investigated the changes in the levels of serum inflammatory mediators responsible for delirium. Serum biomarkers were measured preoperatively to postoperative day 3 in 96 patients who underwent esophageal cancer surgery and compared between patients who did and did not develop delirium. Serum concentrations of the brain-derived phosphorylated neurofilament heavy subunit remained at higher levels throughout the entire perioperative period in patients with delirium (n = 15) than in those without delirium (n = 81). The interaction between delirium and non-delirium was significant for plasminogen activator inhibitor-1 (including age as a covariate, F = 13.360, p < 0.0001, η2 p = 0.134, observed power 1.000) during the perioperative periods. Plasminogen activator inhibitor-1 level discriminated between patients with and without clinically diagnosed delirium with significantly high accuracy (area under curve, 0.864; sensitivity, 1.00: negative predictive value, 1.000; p = 0.002). Rapid increases in the levels of serum plasminogen activator inhibitor-1 may enable clinicians to identify patients at risk of developing postoperative delirium and initiate early prevention and intervention.

Genetic polymorphism of pleiotrophin is associated with pain experience in Japanese adults: Case-control study.

Genetic factors play a role in individual differences in pain experience. Here, we performed a genome-wide association study (GWAS) to identify novel loci regulating pain processing. We conducted a 2-stage GWAS and the candidate single-nucleotide polymorphisms (SNPs) association study on pain experience using an exploratory cohort of patients with cancer pain. The confirmatory cohort comprised of participants from the general population with and without habitual use of analgesic medication. In the exploratory cohort, we evaluated pain intensity using a numerical rating scale, recorded daily opioid dosages, and calculated pain reduction rate. In the confirmatory cohort, pain experience was defined as habitual nonsteroidal anti-inflammatory drug usage. Using linear regression models, we identified candidate SNP in the exploratory samples, and tested the association between phenotype and experienced pain in the confirmatory samples. We found 1 novel SNP (rs11764598)-located on the gene encoding for pleiotrophin on chromosome 7-that passed the genome-wide suggestive significance at 20% false discovery rate (FDR) correction in the exploratory samples of patients with cancer pain (P = 1.31 × 10-7, FDR = 0.101). We confirmed its significant association with daily analgesic usage in the confirmatory cohort (P = .028), although the minor allele affected pain experience in an opposite manner. We identified a novel genetic variant associated with pain experience. Further studies are required to validate the role of pleiotrophin in pain processing.

Serum levels of apolipoprotein A-I and E are associated with postoperative delirium: A post hoc analysis.

Postoperative delirium is a common complication for elderly patients. Detection of phosphorylated neurofilament heavy subunit in the serum reflects axonal damage with postoperative delirium. Although it has been implicated that serum apolipoprotein levels might be associated with senile cognitive disorder, its role in the development of delirium has not been fully investigated. This study examined the association of apolipoproteins with delirium after surgery. This was a post hoc analysis of 117 patients who participated in a prospective observational study of delirium in patients undergoing cancer surgery. Patients were clinically assessed for delirium within the first 5 days of surgery. Serum levels of apolipoprotein A-I, B, and E were measured on postoperative day 3. Forty-one patients (35%) were clinically diagnosed with postoperative delirium. Serum levels of apolipoprotein A-I and B were increased in patients with delirium whereas those of apolipoprotein E were decreased. These changes in apolipoprotein A-I and E levels were associated with the presence of phosphorylated neurofilament heavy subunit in the serum, and were significantly associated with delirium (A-I: adjusted odds ratio [aOR], 6.238; 95% confidence interval [CI], 2.766-20.68; P < .0001; E: aOR, 0.253; 95% CI, 0.066-0.810; P = .0193). A combination of apolipoprotein A-I and E offers significant discrimination between delirium and nondelirium with high accuracy (area under the curve, 0.8899). Serum apolipoprotein A-I and E levels were associated with delirium and the presence of phosphorylated neurofilament heavy subunit in serum. Therefore, apolipoproteins might be useful biomarkers of postoperative delirium.

Gabapentinoid Use Is Associated With Reduced Occurrence of Hyperactive Delirium in Older Cancer Patients Undergoing Chemotherapy: A Nationwide Retrospective Cohort Study in Japan.

BACKGROUND: It is unclear whether gabapentinoids affect the development of delirium. We aimed to determine the association between gabapentinoid use and hyperactive delirium in older cancer patients undergoing chemotherapy. METHODS: We conducted propensity score-matched analyses using data from a nationwide inpatient database in Japan. We included cancer patients with pain ≥70 years of age undergoing chemotherapy between April 2016 and March 2018. Patients receiving gabapentinoids were matched with control patients using propensity scores. The primary outcome was occurrence of hyperactive delirium during hospitalization, and the secondary outcomes were length of hospital stay, in-hospital fractures, and in-hospital mortality. Hyperactive delirium was identified by antipsychotic use or discharge diagnoses from the International Classification of Diseases, 10th Revision. RESULTS: Among 143,132 identified patients (59% men; mean age, 76.3 years), 14,174 (9.9%) received gabapentinoids and 128,958 (90.1%) did not (control group). After one-to-one propensity score matching, 14,173 patients were included in each group. The occurrence of hyperactive delirium was significantly lower (5.2% vs 8.5%; difference in percent, -3.2% [95% confidence interval, -3.8 to -2.6]; odds ratio, 0.60 [0.54-0.66]; P < .001), the median length of hospital stay was significantly shorter (6 days [interquartile range, 3-15] vs 9 days [4-17]; subdistribution hazard ratio, 1.22 [1.19-1.25]; P < .001), and the occurrence of in-hospital mortality was significantly lower in the gabapentinoid group than in the control group (1.3% vs 1.8%; difference in percent, -0.6% [-0.9 to -0.3]; odds ratio, 0.69 [0.57-0.83]; P < .001). Gabapentinoid use was not significantly associated with the occurrence of in-hospital fractures (0.2% vs 0.2%; difference in percent, 0.0% [-0.1 to 0.1]; odds ratio, 1.07 [0.65-1.76]; P = .799). The results of sensitivity analyses using stabilized inverse probability of treatment weighting were consistent with the results of the propensity score-matched analyses. CONCLUSIONS: Our findings suggest that gabapentinoid use is associated with reduced hyperactive delirium in older cancer patients undergoing chemotherapy, with no evidence of an increase in the fracture rate, length of hospital stay, or in-hospital death.