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.

Association between hospital palliative care team intervention volume and patient outcomes.

BACKGROUND: The benefits of palliative care in patients with advanced cancer are well established. However, the effect of the skills of the palliative care team (PCT) on patient outcomes remains unclear. Our aim was to evaluate the association between hospital PCT intervention volume and patient outcomes in patients with cancer. METHODS: A retrospective cohort study was conducted using a nationwide inpatient database in Japan. Patients with cancer receiving chemotherapy and PCT intervention from 2015 to 2020 were included. The outcomes were incidence of hyperactive delirium within 30 days of admission, mortality within 30 days of admission, and decline in activities of daily living (ADL) at discharge. The exposure of interest was hospital PCT intervention volume (annual number of new PCT interventions in a hospital), which was categorized into low-, intermediate-, and high-volume groups according to tertiles. Multivariate logistic regression and restricted cubic-spline regression were conducted. RESULTS: Of 29,076 patients, 1495 (5.1%), 562 (1.9%), and 3026 (10.4%) developed delirium, mortality, and decline in ADL, respectively. Compared with the low hospital PCT intervention volume group (1-103 cases/year, n = 9712), the intermediate (104-195, n = 9664) and high (196-679, n = 9700) volume groups showed significant association with lower odds ratios of 30-day delirium (odds ratio, 0.79 [95% confidence interval, 0.69-0.91] and 0.80 [0.69-0.93], respectively), 30-day mortality (0.73 [0.60-0.90] and 0.59 [0.46-0.75], respectively), and decline in ADL (0.77 [0.70-0.84] and 0.52 [0.47-0.58], respectively). CONCLUSION: Hospital PCT intervention volume is inversely associated with the odds ratios of delirium, mortality, and decline in ADL among hospitalized patients with cancer.

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.

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.

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.

Genetic implications in quality palliative care and preventing opioid crisis in cancer-related pain management.

The prevalence of cancer-related pain is 64% among patients with metastatic, advanced, or terminal cancer, 59% among patients undergoing anticancer treatment, and 33% among patients who completed curative treatment. According to the World Health Organization cancer pain relief guidelines, opioid analgesics are the mainstay analgesic therapy in addition to conventional first-step analgesics, such as non-steroidal anti-inflammatory drugs and acetaminophen. The indications for strong opioids have recently been expanded to include mild-to-moderate pain in addition to moderate-to-severe pain. The U.S. Centers for Disease Control and Prevention guidelines emphasize that realistic expectations should be weighed against potential serious harm from opioids, rather than relying on the unrealized long-term benefits of these drugs. Therefore, treatment strategies for both cancer-related chronic or acute pain have been unfortunately deviated from opioid analgesics. The barriers hindering adequate cancer-related pain management with opioid analgesics are related to the inadequate knowledge of opioid analgesics (e.g., effective dose, adverse effects, and likelihood of addiction or tolerance). To achieve adequate opioid availability, these barriers should be overcome in a clinically suitable manner. Genetic assessments could play an important role in overcoming challenges in opioid management. To balance the improvement in opioid availability and the prevention of opioid misuse and addiction, the following two considerations concerning opioids and genetic polymorphisms warrant attention: (A) pain severity, opioid sensitivity, and opioid tolerance; and (B) vulnerability to opioid dependence and addiction.

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.

A decision tree prediction model for a short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions: A secondary analysis of a multicenter and prospective observational study (Phase-R).

OBJECTIVE: There is no widely used prognostic model for delirium in patients with advanced cancer. The present study aimed to develop a decision tree prediction model for a short-term outcome. METHOD: This is a secondary analysis of a multicenter and prospective observational study conducted at 9 psycho-oncology consultation services and 14 inpatient palliative care units in Japan. We used records of patients with advanced cancer receiving pharmacological interventions with a baseline Delirium Rating Scale Revised-98 (DRS-R98) severity score of ≥10. A DRS-R98 severity score of <10 on day 3 was defined as the study outcome. The dataset was randomly split into the training and test dataset. A decision tree model was developed using the training dataset and potential predictors. The area under the curve (AUC) of the receiver operating characteristic curve was measured both in 5-fold cross-validation and in the independent test dataset. Finally, the model was visualized using the whole dataset. RESULTS: Altogether, 668 records were included, of which 141 had a DRS-R98 severity score of <10 on day 3. The model achieved an average AUC of 0.698 in 5-fold cross-validation and 0.718 (95% confidence interval, 0.627-0.810) in the test dataset. The baseline DRS-R98 severity score (cutoff of 15), hypoxia, and dehydration were the important predictors, in this order. SIGNIFICANCE OF RESULTS: We developed an easy-to-use prediction model for the short-term outcome of delirium in patients with advanced cancer receiving pharmacological interventions. The baseline severity of delirium and precipitating factors of delirium were important for prediction.

Characteristics of taste alterations in people receiving taxane-based chemotherapy and their association with appetite, weight, and quality of life.

PURPOSE: There is limited evidence on the effect of chemotherapy-associated taste alteration. This study aimed to evaluate taste alteration characteristics in patients receiving taxane-based chemotherapy and investigate the association of taste alterations with appetite, weight, quality of life (QOL), and adverse events. METHODS: This cross-sectional study evaluated 100 patients receiving paclitaxel, docetaxel, or nab-paclitaxel as monotherapy or combination therapy. Taste alterations were evaluated using taste recognition thresholds and severity and symptom scales. Taste recognition thresholds, symptoms, appetite, weight, and adverse events were compared between patients with and without taste alterations, and logistic regression analysis was performed to identify risk factors. RESULTS: Of the 100 patients, 59% reported taste alterations. We found significantly elevated taste recognition thresholds (hypogeusia) for sweet, sour, and bitter tastes in the taste alteration group receiving nab-paclitaxel (p = 0.022, 0.020, and 0.039, respectively). The taste alteration group reported general taste alterations, decline in basic taste, and decreased appetite. Neither weight nor QOL was associated with taste alterations. Docetaxel therapy, previous chemotherapy, dry mouth, and peripheral neuropathy were significantly associated with taste alterations. CONCLUSIONS: Almost 60% of patients receiving taxane-based regimens, especially docetaxel, reported taste alterations. Taste alteration affected the patient's appetite but did not affect the weight or QOL. Docetaxel therapy, previous chemotherapy, dry mouth, and peripheral neuropathy were independent risk factors for taste alterations.

Development of a severity discrimination scale based on physical quality of life for patients with chronic pain.

BACKGROUND: Deterioration of quality of life in patients with chronic pain is difficult to treat. Chronic pain in patients with low quality of life may be "severe" and require multidisciplinary treatments. This study aimed to develop an objective severity discrimination scale based on quality of life measurements to identify patients with "severely disabling" chronic pain. METHODS: Subjects were 156 patients with chronic pain whose numerical rating pain score was ≥1 and who had pain for ≥3 months. Diseases associated with chronic pain included spinal diseases, joint diseases, concomitant diseases, complex regional pain syndromes, and other musculoskeletal diseases. Patients were divided into low, middle, and high groups based on physical quality of life summary scores on the Short Form-36. The mental component summary, painDETECT, Japanese version of the Pain Catastrophizing Scale, Brief Scale for Psychiatric Problems in Orthopaedic Patients, and factors related to degree/quality of pain during the past 4 weeks were analyzed to identify components in the low group. The score weighting factor for discriminating between the high and low groups was determined by discriminant analysis. RESULTS: Factor analysis identified 4 factors representing features of chronic pain patients with low QOL: enhanced perception of pain, pain catastrophic thoughts, depressive sleep disorder, and pain intensity. For discriminant analysis, patients were defined as those with low physical quality of life if each factor's total score multiplied by a factor plus a constant value of 2.6 was ≥0, and high quality of life if it was <0. The receiver operating characteristic curve area used to determine the cut-off value was 0.71, with 67.3% sensitivity and specificity. CONCLUSIONS: We developed a 33-question severity discrimination scale to define "severely disabling" chronic pain based on physical quality of life. "Severely disabling" patients identified on this scale could represent chronic pain patients needing focused multidisciplinary treatment.

Direct evidence of EEG coherence in alleviating phantom limb pain by virtual referred sensation: Case report.

Virtual reality (VR) systems have been integrated into rehabilitation techniques for phantom limb pain (PLP). In this case report, we used electroencephalography (EEG) to analyze corticocortical coherence between the bilateral sensorimotor cortices during vibrotactile stimulation in conjunction with VR rehabilitation in two PLP patients. As a result, we observed PLP alleviation and increased alpha wave coherence during VR rehabilitation when stimulation was delivered to the cheek and shoulder (referred sensation areas) of the affected side. Vibrotactile stimulation with VR rehabilitation may enhance the awareness and movement of the phantom hand.

A Novel Technique Using Magnetic Resonance Imaging in the Supine and Prone Positions for Diagnosing Lumbar Adhesive Arachnoiditis: A Preliminary Study.

BACKGROUND: Lumbar adhesive arachnoiditis is a debilitating neuropathic condition and is difficult to diagnose owing to lack of definitive diagnostic criteria. By focusing on the intrathecal mobility of nerve roots, we assessed whether useful diagnostic criteria could be established using MRI. METHODS: Seventeen patients with a high risk for lumbar adhesive arachnoiditis and 18 no-risk patients with chronic low back pain and/or leg pain participated in this study. The patients underwent MRI in both the supine and prone positions. Eleven axial T2-weighted images between the L2 and L5/S levels were obtained, and the proportion of the low-intensity area in the dorsal half to the total low-intensity area in the dural sac was calculated for each axial view. RESULTS: At some lumbar levels, the low-intensity area in the dorsal half of the dural sac was relatively larger in patients with a high risk for lumbar adhesive arachnoiditis than in the no-risk patients. In the no-risk group, the proportion of the low-intensity area in the dorsal half in the supine position was significantly higher than that in the prone position at all lumbar levels. However, in the high-risk group, at some levels, the proportions were not significantly different in the dorsal half of the dural sac between the supine and prone positions. CONCLUSION: In patients with a known risk for lumbar adhesive arachnoiditis, nerve roots lose their potential to migrate in the dural sac in the gravitational force direction on MRI.

Characteristics of Phantom Limb Pain Alleviated with Virtual Reality Rehabilitation.

OBJECTIVES: Neurorehabilitation techniques using virtual reality (VR) systems have recently become widespread as a rehabilitation method for restoring phantom limb movement and alleviating phantom limb pain (PLP). However, analgesic effects have varied between studies, possibly because of differences in the characteristics of PLP between patients (e.g., cramping, burning, shooting). We aimed to reveal the relationship between VR effects and PLP characteristics using an exploratory factor analysis. METHODS: PLP characteristics of 19 patients were measured using the Short-Form McGill Pain Questionnaire (SF-MPQ), and all PLP patients performed the VR rehabilitation protocol for 20 minutes. During VR rehabilitation, mirror-reversed computer graphic images of an intact arm (the virtual phantom limb) were presented to patients via a head-mounted display, inducing the perception of voluntary execution of movements of their phantom limb when intending bimanual movements. RESULTS: VR rehabilitation significantly restored movement representation (P < 0.0001) quantified using the bimanual coupling effect and significantly alleviated PLP intensity (P < 0.0001). The factor analysis revealed that PLP characteristics could be divided into two factors: "somatosensory-related pain characteristics" and "kinesthesia-related pain characteristics." PLP alleviation via VR rehabilitation was significantly correlated with "kinesthesia-related pain characteristics" (r = 0.47, P = 0.02) but not "somatosensory-related pain characteristics" (r = 0.22, P = 0.17). CONCLUSIONS: The current findings indicate that VR rehabilitation may be particularly effective for PLP associated with distorted phantom limb movement and body representations (e.g., clamping, gnawing), compared with typical neuropathic sensations (e.g., shooting, burning, dysesthesia).

Resistin Is a Novel Marker for Postoperative Pain Intensity.

BACKGROUND: Pro- and anti-inflammatory cytokines (adipokines) associated with adipose tissue can modulate inflammatory processes and lead to systemic inflammatory conditions such as metabolic syndrome. In the present pilot study, we investigated 3 major adipokines (leptin, adiponectin, and resistin) and 2 nonspecific proinflammatory cytokines (tumor necrosis factor α and interleukin-6) with regard to their association with postoperative pain intensity. METHODS: We analyzed a total of 45 single-nucleotide polymorphisms of the adipokines in 57 patients with postlaparotomy pain. We adjusted for multiple testing to reduce the chance of false-positive results by controlling the false discovery rate. Serum levels of the adipokines and proinflammatory cytokines were measured in another 36 patients undergoing laparotomy. A stepwise multiple linear regression analysis using these measurements and opioid dosages as independent variables was performed to explore the factors associated with postoperative pain. RESULTS: Only 1 variant of the resistin gene (rs3745367) demonstrated a significant association with postoperative pain (P < .002). Patients exhibiting homozygosity for the minor alleles (n = 7; numerical rating scale [NRS], 2.3 ± 1.3) demonstrated lower pain intensity compared with those exhibiting homozygosity for the major alleles (n = 29; NRS, 3.8 ± 1.0; P = .004) and heterozygosity for the minor alleles (n = 21; NRS, 4.2 ± 0.8; P < .001). Only serum resistin levels showed a positive association with postoperative pain. CONCLUSIONS: A genetic variant of resistin and serum resistin levels were associated with postoperative pain intensity, while other adipokines and cytokines exhibit no such association. Resistin can alter the inflammatory responses in postoperative wounds, although it could be a determinant factor that is independent of inflammatory processes. Resistin may be a novel marker for postoperative pain intensity.

Kinesiophobia modulates lumbar movements in people with chronic low back pain: a kinematic analysis of lumbar bending and returning movement.

PURPOSE: We aimed to kinematically analyze lumbar bending and returning movements and clarify the relationship between fear of movement and kinematic output. METHODS: We recruited 45 participants with CLBP (i.e., > 6 months) and 20 healthy control (HC) participants with no history of CLBP. We used the numerical rating pain scale (NRS), Tampa Scale for Kinesiophobia (TSK-11), and Pain Self-Efficacy Questionnaire (PSEQ-2) as qualitative outcome measurements. CLBP participants were divided into two subgroups (high- and low-fear groups) based on the median split of the total TSK-11 score. In the kinematic recording session, a starting-cue beep signaled participants to bend forward using the lumbar region of their spine and then return to an upright posture, and we used a flexible twin-axis electrogoniometer to record the lumbar movements. The time series of lumbar movements was divided into four phases according to lumbar movement velocity, and we calculated the length (sec) of each phase. RESULTS: Phase 1 (duration prior to cue-induced movement initiation) and phase 3 (switch in the direction of lumbar movement from forward to backward) were significantly longer in the CLBP high-fear group compared with those in the CLBP low-fear group and HC group (p < 0.05). The increased lengths of these two phases were positively correlated with not only pain intensity but also TSK-11 scores (p < 0.05). CONCLUSIONS: These results represent evidence of a particular lumbar movement pattern associated with kinesiophobia. These results might help to identify psychological factors that impact lumbar movement patterns in individuals with CLBP. These slides can be retrieved under Electronic Supplementary Material.

Correction to: Kinesiophobia modulates lumbar movements in people with chronic low back pain: a kinematic analysis of lumbar bending and returning movement.

In the figure 2, "CLBP Low fear" located at the right end of Time of Phase 1 is wrong. The correct statement is "CLBP High fear". The complete correct figure 2 is given below.

Kinematic evaluation for impairment of skilled hand function in chemotherapy-induced peripheral neuropathy.

INTRODUCTION: Chemotherapy-induced peripheral neuropathy (CIPN) usually affects both sensory and motor function of hands and feet, resulting in impaired skilled hand function (e.g., typing a keyboard). However, quantitative and objective evaluations for this condition have not been established. PURPOSE OF THE STUDY: We evaluated skilled hand function using a kinematic analysis and investigated relationships among hand kinematic function and the clinical sensory and motor features of CIPN. STUDY DESIGNS: Clinical measurement. METHODS: Twelve CIPN patients and 12 age-matched control participants were enrolled. We recorded their reach and grasp movements using a three-dimensional measurement system, and calculated the normalized jerk of these movements as quantitative indexes of skilled hand function. Additionally, we used the number of sequential hand grip-release cycles in 10 seconds as an evaluation of clinical motor function. RESULTS: Our kinematic analyses revealed significant difference in normalized jerk of grasp movement (CIPN: 3.7 ± 0.2, control: 3.4 ± 0.1; P = .005), but this was not the case for reach movement (CIPN: 2.5 ± 0.1, control: 2.5 ± 0.2; P = .43), indicating that the distal part of the forearm is particularly affected in CIPN. Such disturbed grasp movement was directly correlated with poor scores on the hand grip-release test and the sensory tests. DISCUSSION: We revealed deficit impaired hand function objectively and quantitatively in CIPN patients using a kinematic analysis. Further, the hand grip test could represent such kinematic abnormality and could be useful for evaluating skilled hand function of CIPN patients. CONCLUSIONS: Our kinematic and clinical measurements objectively and quantitatively evaluate skilled hand function in individuals with CIPN in clinical settings. LEVEL OF EVIDENCE: Cross-sectional observational study.

A "matched" sensory reference can guide goal-directed movements of the affected hand in central post-stroke sensory ataxia.

Patients with central post-stroke sensory ataxia (CPSA) suffer from not only somatosensory dysfunction but also the ataxic movement disorder of the affected limb. These sensory and motor impairments possibly interfere each other, but such interference is still unclear. We evaluated smoothness of grasp movements in CPSA patients using a kinematic analysis, and verified the effect of somatosensory reference from the intact hand on grasp movements. Eight CPSA patients were enrolled. We recorded their reach-and-pinch movements of both affected and intact hands toward the tip of the 3-cm-diameter vertical bar, using a three-dimensional measurement system. When executing these movements of one hand, the patients simultaneously pinched the same diameter bar as the goal tip (matched-reference condition: Matched-Ref) or the 5-cm-diameter thicker bar (mismatched-reference condition: Mismatched-Ref) by the other hand. The normalized jerk index (i.e., movement smoothness) of the affected hand was disturbed compared with the intact hand. The kinematic data of the finger opening and closing phases were also disturbed. These disturbances were partially improved with Matched-Ref but not Mismatched-Ref of the intact hand. We successfully evaluated the features of CPSA, indicating that the somatosensory reference method could be useful for rehabilitation in sensory ataxia.

Association Between Polymorphisms in the Purinergic P2Y12 Receptor Gene and Severity of Both Cancer Pain and Postoperative Pain.

Background: Despite the widespread use of opioids for the treatment of cancer pain, results from several surveys consistently show that pain is still prevalent in some patients with malignant diseases. The purinergic P2Y12 receptor is a primary site leading to microglial activation and hyperalgesic pain behaviors and is considered a key regulator in the prevention of the aggravation of clinical pain conditions. Genetic variability in the P2RY12 gene may contribute to individual differences in pain and opioid sensitivity. Methods: We genotyped 31 single nucleotide polymorphisms (SNPs) throughout the P2RY12 gene and compared genotypes against pain measurements and opioid requirements in Japanese cancer pain patients (N = 90). The most promising SNP association with pain severity was validated by genotyping an additional postoperative pain patient cohort (N = 355). Results: Five SNPs (rs3732765, rs9859538, rs17283010, rs11713504, and rs10935840) of the P2RY12 gene were significantly associated with cancer pain severity, although opioid requirements were comparable in each genotype of the five SNPs. The alleles of these SNPs represented one absolute linkage disequilibrium block of the P2RY12 gene. In the second association study of postoperative pain, subjects carrying the minor T allele of the rs3732765 SNP demonstrated more intense 24-hour postoperative pain compared with subjects not carrying this allele although total 24-hour postoperative opioid consumptions based on weight were comparable. Conclusions: Polymorphisms of the P2RY12 gene may predict individual differences in both cancer and postoperative pain severity; this might be caused by functional alteration of nociceptive neurons through neuron-glia interaction.

Executive summary of the Clinical Guidelines of Pharmacotherapy for Neuropathic Pain: second edition by the Japanese Society of Pain Clinicians.

Neuropathic pain has a substantial effect on quality of life (QOL). The Japanese Society of Pain Clinicians (JSPC) has developed clinical guidelines of pharmacotherapy for neuropathic pain. These guidelines offer clarity on recommendations based on both the most recent scientific evidence and expert opinions. Understanding the concept, disease entity, and burden of neuropathic pain, as well as its screening and diagnosis are important steps before starting pharmacotherapy. As well as other guidelines, the guidelines propose several lines of pharmacotherapies in a step-wise manner. To name a few different points, our guidelines propose an extract from inflamed cutaneous tissue of rabbits inoculated with vaccinia virus, which has been found to be effective for post-herpetic neuralgia in Japan, as one of the second-line drugs. When prescribing opioid analgesics, proposed as the third-line drugs, for neuropathic pain, the guidelines recommend physicians continue evaluations on either abuse or addiction. The guidelines do not recommend concomitant use of nonsteroidal anti-inflammatory drugs and acetaminophen because of lack of clinical evidence of their efficacy. If patients do not respond well to pharmacotherapy, which is prescribed in a step-wise manner, other treatment strategies should be considered to improve patients' activities of daily living and QOL.