Effects of taxane-induced peripheral neuropathy on hand dexterity impairment: evaluation of quantitative and subjective assessments.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) commonly involves hand dexterity impairment. However, the factors affecting hand dexterity impairment are unknown and there is currently no established treatment. The purpose of the current study was to clarify factors influencing hand dexterity impairment in taxane-induced peripheral neuropathy using subjective and objective assessments. METHODS: We assessed patient characteristics, treatment-related factors, subjective symptoms of CIPN (Patient Neurotoxicity Questionnaire [PNQ]), psychological symptoms, and upper limb dysfunction (Quick Disabilities of the Arm, Shoulder and Hand [Quick DASH]). Quantitative assessments were pinch strength, sensory threshold, hand dexterity impairment, and grip force control. Multiple regression analysis was performed using hand dexterity impairment as the dependent variable and age and PNQ, Quick DASH, and control of grip force as independent variables. RESULTS: Forty-three breast cancer patients were included in the analysis. Hand dexterity impairment in taxane-induced peripheral neuropathy patients was significantly correlated with age, grip force control, and PNQ sensory scores (p < 0.008). Multiple regression analysis demonstrated that PNQ sensory scores and grip force control were significantly associated with hand dexterity impairment (p < 0.01). CONCLUSION: Subjective symptoms (numbness and pain) and grip force control contributed to impaired hand dexterity in taxane-induced peripheral neuropathy.

Central Sensitization in Cancer Survivors and Its Clinical Implications: State of the Art.

Although the prevalence of cancer pain is 47% after treatment, cancer pain is often underestimated, and many patients are undertreated. The complexity of cancer pain contributes to the lack of its management. Recently, as the mechanism of cancer pain, it has become clear that central sensitization (CS) influences chronic pain conditions and the transition from acute to chronic pain. In this state-of-the-art review, we summarized the association of CS or central sensitivity syndrome with pain and the treatment for pain targeting CS in cancer survivors. The management of patients with CS should not only focus on tissue damage in either the affected body regions or within the central nervous system; rather, it should aim to target the underlying factors that sustain the CS process. Pain neuroscience education (PNE) is gaining popularity for managing chronic musculoskeletal pain and could be effective for pain and CS in breast cancer survivors. However, there is a study that did not demonstrate significant improvements after PNE, so further research is needed. Precision medicine involves the classification of patients into subgroups based on a multifaceted evaluation of disease and the implementation of treatment tailored to the characteristics of each patient, which may play a central role in the treatment of CS.

Predictors of persistent post-surgical pain intensity and interference at 1 year after breast cancer surgery: assessing central sensitization, central sensitivity symptoms, and psychological factors.

BACKGROUND: Persistent post-surgical pain (PPSP) is associated with upper limb dysfunction and decreased quality of life and causes long-term suffering for breast cancer survivors after surgery. However, the predictors of PPSP remain unclear. The purpose of this study was to examine predictors of PPSP intensity and interference at 1 year postoperatively, focusing on treatment-related factors, pre- and postoperative central sensitization (CS), CS-related symptoms (e.g., muscle stiffness, fatigue, sleep disturbances), and psychological factors. METHODS: Eighty-eight women with planned unilateral breast cancer surgery were included in this longitudinal study. CS, CS-related symptoms, and psychological factors were assessed preoperatively, 1 month postoperatively, and 1 year postoperatively. Analysis of covariance was used to compare the groups with and without PPSP, accounting for treatment-related factors. Multiple regression analysis was performed to identify predictors of PPSP intensity and interference at 1 year postoperatively. RESULTS: Even after adjusting for covariates, preoperative and 1-month postoperative Central Sensitization Inventory scores in the PPSP group were significantly higher than scores in the group without PPSP. Multiple regression analysis showed that axillary lymph node dissection (ALND) and 1-month postoperative CS-related symptoms were independent predictors of PPSP intensity and interference at 1 year postoperatively (p < 0.01). CONCLUSION: We found that ALND and 1-month postoperative CS-related symptoms were predictors of PPSP intensity and interference at 1 year postoperatively.

Does a combination of self-reported signs related to central sensitization and pressure pain threshold allow for a more detailed classification of pain-related characteristics in patients with chronic musculoskeletal pain?: A cross-sectional study.

OBJECTIVES: The clinical utility of combining the central sensitization (CS) inventory (CSI) with the pressure pain threshold (PPT) in assessing the effect of central sensitization on pain is unknown. This study aimed to investigate the effects of CSI, PPT, and their interaction on pain and the characteristics of clinical symptoms in patients with chronic musculoskeletal pain grouped according to the CSI score and PPT value. METHOD: A total of 187 participants with chronic musculoskeletal pain were recruited. PPT, brief pain inventory, widespread pain index, pain catastrophizing scale, EuroQol-5 dimension, and CSI were assessed. Multiple regression analyses were performed using pain intensity and interference scores as dependent variables and the CSI score and PPT value as independent variables. Hierarchical cluster analysis was also performed to classify the participants into subgroups according to the CSI score and PPT value. Following the classification, pain-related characteristics and health-related QOL were compared among the subgroups. RESULTS: Multiple regression analyses demonstrated that only the CSI score significantly affected pain intensity and interference. As a result of the cluster analysis, three groups were identified: cluster 1 (n = 61, CSI low/PPT low group), cluster 2 (n = 78, CSI low/PPT high group), and cluster 3 (n = 48, CSI high/PPT low group). The CSI high/PPT low group had a higher incidence of pain-related symptoms than the CSI low group regardless of the PPT value. CONCLUSIONS: Combined CSI and PPT may not fully allow a detailed classification of pain-related characteristics. The CSI may be clinically more useful for assessing the effect of CS on pain-related symptoms.

Combination of Pain Location and Pain Duration is Associated with Central Sensitization-Related Symptoms in Patients with Musculoskeletal Disorders: A Cross-Sectional Study.

OBJECTIVES: Increased evidence indicates that pain location affects central sensitization (CS)-related symptoms. In addition, pain location and pain duration may be intricately related to CS-related symptoms. However, these factors have been investigated separately. This study aimed to investigate the association between CS-related symptoms and pain location and/or pain duration in patients with musculoskeletal disorders. METHODS: Six hundred thirty-five participants with musculoskeletal disorders were included in this cross-sectional study. All participants were assessed for pain location, pain duration, central sensitization inventory (CSI), EuroQol-5 dimension, and brief pain inventory. The participants were categorized into 3 groups based on pain location (spinal, limb, and both spinal and limb pain) and into 2 groups based on pain duration (acute and chronic pain). RESULTS: The interaction between pain location and pain duration were not significant on CSI score (P > 0.05). The odds ratio for higher CSI score (≥ 40) in patients with both spinal and limb pain vs. those with spinal or limb pain was 2.64 (P < 0.01) and that in patients with chronic pain vs. those with acute pain was 1.31 (P = 0.52). In addition, the prevalence of higher CSI scores in the combination of chronic and "both spinal and limb" pain was high (23.1%, adjusted residual = 4.48). CONCLUSIONS: Pain location independently influenced CSI scores, and the combination of both spinal and limb pain and chronic pain indicated high CSI scores. The combination of pain location and pain duration is an important clue that points to CS-related symptoms.

Effect of perioperative pain neuroscience education in patients with post-mastectomy persistent pain: a retrospective, propensity score-matched study.

PURPOSE: Central sensitization (CS)-related symptoms and pain catastrophizing contribute to persistent post-mastectomy pain (PPMP). Pain neuroscience education (PNE) is effective in reducing CS-related symptoms and pain catastrophizing in patients with chronic pain. However, to date, no intervention study of PNE has been conducted to patients with PPMP. This study was aimed to examine whether PNE is more effective than biomedical education (BME) for PPMP. METHODS: In this retrospective case-control study, 118 patients were included. We intervened different patients at different times as follows: (1) a BME group (n = 58) of patients who received BME combined with physiotherapy and (2) a PNE group (n = 60) of patients who received PNE combined with physiotherapy. One year after surgery, we assessed pain intensity and interference (brief pain inventory [BPI]), CS-related symptoms (central sensitization inventory [CSI]), and pain catastrophizing (pain catastrophizing scale [PCS]). Propensity score matching was used to reduce or minimize selection bias and confounding biases and to make the number of cases in both groups match 1:1. RESULTS: Propensity score matching generated the BME group (n = 51) and the PNE group (n = 51). The BPI score, CSI score, and PCS score were statistically significantly lower in the PNE group than in the BME group (all, p < 0.05). The effect sizes for the BPI intensity (r = 0.31) were moderate. CONCLUSIONS: PNE resulted in a better outcome of pain management with less functional disability and CS-related symptoms compared to BME after breast surgery.

Cutoff Value for Short Form of Central Sensitization Inventory.

OBJECTIVES: This study aimed to determine the optimal cutoff score of the 9-item short version of the CSI, the CSI-9, by comparing patients with central sensitivity syndrome (CSS) not only to healthy volunteers as with the original version, but also to patients with musculoskeletal (MSK) disorders. METHODS: All participants filled out the CSI, EuroQol 5-dimension, Brief Pain Inventory, and Pain Catastrophizing Scale questionnaires. To identify a clinically relevant cutoff score, receiver operating characteristic analyses were conducted. The area under the curve was used to examine the ability of the CSI-9 to distinguish patients with fibromyalgia (FM) from patients with MSK disorders and healthy individuals. RESULTS: Twenty-six participants with FM, 30 patients with MSK disorders, and 28 healthy individuals were included. We determined 2 cutoff scores: 20 for distinguishing patients with FM from patients with MSK disorders and 17 for distinguishing patients with FM from healthy individuals. These cutoff scores had good sensitivity (patients with MSK disorders, 92.3%; healthy individuals, 96.2%) and specificity (patients with MSK disorders, 93.3%; healthy individuals, 100%). In addition, the patients who scored above the cutoff of 20 points exhibited worse clinical symptoms (higher pain intensity, higher pain interference, higher Pain Catastrophizing Scale scores, and lower EuroQol 5-dimension scores) than those who scored below it. Furthermore, a significantly higher number of subjects who scored more than 20 on the CSI-9 had a history of 2 or more diagnoses of CSS. CONCLUSION: The optimal CSI-9 cutoff score of 20 is beneficial to clinicians in the evaluation of central sensitization-related symptoms. The cutoff score helps to identify patients who need additional treatments, such as pain neuroscience education and cognitive behavioral therapy.

Perceived Body Distortion Rather Than Actual Body Distortion Is Associated With Chronic Low Back Pain in Adults With Cerebral Palsy: A Preliminary Investigation.

OBJECTIVES: The aim of the present study was to investigate whether distorted body perception is a feature of the low back pain (LBP) experience in people with cerebral palsy (CP) and whether any distortions noted are confounded by the presence of motor and postural impairments commonly seen in CP. METHODS: Forty-five individuals participated in this study: 15 adults with CP with LBP (CP_Pain group), 15 adults with CP without LBP (CP_noPain group), and 15 age-matched adults with LBP but no CP (Pain group). Body perception was evaluated using the Fremantle Back Awareness Questionnaire (FreBAQ) and by assessing 2-point discrimination thresholds over the low back. A comprehensive assessment of motor function was also undertaken in the CP population, and postural function was assessed in all 3 groups. RESULTS: Significant differences between the 3 groups were found for FreBAQ scores (P < 0.0001). The TPD threshold in the low back of the CP_Pain group was significantly larger than that of the CP_noPain group (P = 0.01), though we found no difference between the CP_noPain group and the Pain group (P = 0.21). We found no difference in motor or postural function between the 2 CP groups. DISCUSSION: The present results suggest that body image is disrupted in people with CP who experience LBP. The disruptions in perception were similar to those seen in people with LBP and no CP, suggesting that the distortions may be more related to the presence of pain than the presence of CP.

Difference in the impact of central sensitization on pain-related symptoms between patients with chronic low back pain and knee osteoarthritis.

Purpose: The aims of the present study were to investigate whether the association between the Central Sensitization Inventory (CSI) score, pain-related symptoms, pain-related disability, and health-related quality of life differed by disease (chronic low back pain [CLBP] vs knee osteoarthritis [KOA]), and to determine optimal cutoff scores for the CSI reflecting disease-specific characteristics. Patients and methods: A total of 104 patients with CLBP and 50 patients with KOA were recruited. Central sensitization-related symptoms (CSI), EuroQol 5-dimension (EQ-5D), Brief Pain Inventory, widespread pain (Widespread Pain Index [WPI]), pressure pain threshold (PPT), and temporal summation (TS) were assessed and compared between the CLBP and KOA groups. Univariate correlation analysis was performed in each group. The receiver operating characteristic (ROC) curve analysis was performed to identify 1) presence/absence of central sensitization (CS), 2) presence/absence of central sensitivity syndromes (CSSs), and 3) pain intensity and pain interference in each group. Results: The CSI and WPI scores were significantly higher in the CLBP group than in the KOA group. EQ-5D and pain interference scores significantly correlated with the CSI score in both the CLBP and KOA groups. The WPI score, PPT, and TS did not correlate with the CSI score in either the CLBP or KOA group. The suggested cutoff scores were 28 in the CLBP group and 17 in the KOA group to identify presence or absence of CSSs, and 34 in the CLBP group and 18-19 in the KOA group to identify pain severity. Conclusion: The impact of CS on pain could differ between CLBP and KOA and that cutoff scores differ by each parameter we attempted to identify. Therefore, we should use the appropriate cutoff scores for the purposes and consider the difference in the impact of CS on pain by the patient group.

The central sensitization inventory predict pain-related disability for musculoskeletal disorders in the primary care setting.

BACKGROUND: Central sensitization (CS) is found in patients with musculoskeletal disorders and is related to clinical symptoms, including pain-related disability. The Central Sensitization Inventory (CSI) has been developed for patients who are at risk of symptoms related to CS, and CSI severity levels are suggested for clinical interpretation of the CSI score. However, the longitudinal relationship between CSI severity and pain-related disability is unclear in primary care. In this study, we investigated the association between CSI severity levels and the profiles of patients with musculoskeletal disorders as well as the longitudinal relationship between CSI severity levels and pain-related disability in primary care settings. METHODS: A total of 553 patients were assessed using CSI, EuroQol-5 dimension (EQ5D), and Brief Pain Inventory (BPI). Of the 553 patients, 150 patients were reassessed at the 3-month follow-up. Patients were grouped into three severity levels according to baseline CSI score: subclinical, mild, and moderate to higher level. RESULTS: As the CSI severity levels increased, the clinical symptoms tended to worsen on cross-sectional analysis (p < 0.05). Pain-related disability at the 3-month follow-up was significantly higher for patients with moderate to high baseline CSI severity levels than for patients with subclinical baseline CSI levels (p < 0.001). Furthermore, pain-related disability increased according to the CSI severity level, with a medium to large effect size. However, there were no differences in pain duration across the CSI severity levels. CONCLUSIONS: CSI has clinical utility as a prediction tool regardless of pain duration in patients with musculoskeletal disorders in primary care settings. SIGNIFICANCE: Higher CSI severity levels predicted higher pain-related disability for patients with musculoskeletal disorders in a primary care setting. CSI is a clinically useful prediction tool in patients with musculoskeletal disorders.

Comparison of central sensitization-related symptoms and health-related quality of life between breast cancer survivors with and without chronic pain and healthy controls.

BACKGROUND: In breast cancer survivors, multiple risk factors for health-related quality of life (HRQoL) and chronic pain, including cancer treatment-related factors, psychosocial factors, and central sensitization (CS), have been suggested; however, there has been no comparative study between breast cancer survivors with and without pain. This study aimed to compare the demographic characteristics, psychological factors, and CS-related symptoms between breast cancer survivors with pain, those without pain, and healthy controls, and to investigate the relationships of these factors with HRQoL. METHODS: We conducted a cross-sectional survey of 218 women, including patients who underwent breast cancer surgery and adjuvant therapy and healthy women. RESULTS: Patients were divided into the pain group (n = 42), without-pain group (n = 51), and healthy group (n = 47); thus, among breast cancer survivors, 45% reported chronic pain. The proportion of participants who received breast cancer treatments, such as axillary lymph node dissection and chemotherapy, was higher in the pain group than in the without-pain group (p < 0.05). The Central Sensitization Inventory (CSI) and psychosocial factors in the pain group were higher than those in the without-pain group and healthy group (p < 0.01). The CSI and PCS showed larger effect sizes than treatment-related factors. Moreover, HRQoL was significantly correlated with CSI, PCS, Patient Health Questionnaire-2, and Generalized Anxiety Disorder-2 scale (all, p < 0.01). On multiple linear regression analysis, CSI accounted for 43% of the variance in HRQoL. CONCLUSIONS: CS and pain catastrophizing may be more associated with the development and/or maintenance of persistent pain than treatment-related factors.

Validation of the Japanese version of the life satisfaction checklist (LiSat-11) in patients with low back pain: A cross-sectional study.

BACKGROUND: Previous studies suggest that life satisfaction assessment using the Life Satisfaction checklist (LiSat-11) is a meaningful outcome measure and may play an important role in setting rehabilitation goals in patients with chronic pain. Until now, there was no Japanese version of this questionnaire, and the psychometric properties of the original version of the LiSat-11 have only been investigated using classical test theory approaches. The objective of the present study was to evaluate the psychometric properties of the LiSat-11-J using Rasch analysis in a sample of Japanese people with low back pain (LBP). METHODS: One hundred and two participants with LBP completed the LiSat-11-J. Concurrent Validity of the LiSat-11-J was investigated by examining the relationships between the LiSat-11-J and clinical valuable. Rasch analysis was used to assess targeting, category ordering, unidimensionality, person fit, internal consistency, and differential item functioning. RESULTS: The LiSat-11-J was significantly correlated with disability, pain-related catastrophizing, fear of movement, anxiety, and depression. The LiSat-11-J targeted the participants with low life satisfaction and had unidimensionality, good internal consistency, and good test-retest reliability. Responses to category 1 ("very dissatisfying") and 2 ("dissatisfying") were disordered. After collapsing these two categories into a single new category, targeting function and category order showed a little improvement. CONCLUSION: The LiSat-11-J has unidimensionality, acceptable internal consistency, good test-retest reliability, and concurrent validity to the assessment of pain-related disability and psychological factors. However, targeting function and category order were not well. These two components showed improvement by rescoring category, but not sufficient. These results suggest that the LiSat-11-J is not well adequate to apply as an assessment tool of life satisfaction to the patients with LBP.

Development and psychometric properties of short form of central sensitization inventory in participants with musculoskeletal pain: A cross-sectional study.

BACKGROUND: The central sensitization inventory (CSI) comprises 25 items and is commonly used to measure somatic and emotional symptoms related to central sensitization symptoms. CSI was developed as an easy-to-administer screening instrument for patients at high risk of developing central sensitization in whom it was essential to quickly evaluate the condition. The purpose of the present study was to develop a short form of CSI and evaluate its psychometric properties using a contemporary approach called Rasch analysis. METHODS: A total of 505 patients with musculoskeletal disorders were recruited in this study. The CSI, pain intensity, pain interference, and the health-related quality of life (QOL) were evaluated for each participant. The original CSI items were consecutively analyzed using the Rasch model. Successive Rasch analyses were performed until a final set of items satisfied the model fit requirements. We also analyzed the psychometric properties of the original and short forms of CSI. RESULTS: Four consecutive Rasch analyses identified the removable items. Finally, the shortest questionnaire obtained that maintained the correct psychometric properties based on the Rasch model contained only 9 items (CSI-9). Rasch analysis showed that the CSI-9 had acceptable internal consistency, exhibited unidimensionality, had no notable differential item functioning, and was functional on the category rating scale. CONCLUSIONS: The nine-item short form of CSI has acceptable psychometric properties and is suitable for use for patients with musculoskeletal pain. Thus, the CSI-9 can be used as a brief instrument to evaluate central sensitization.

Validation of the Japanese version of the Central Sensitization Inventory in patients with musculoskeletal disorders.

BACKGROUND: Many musculoskeletal pain conditions are characterized by hypersensitivity, which is induced by central sensitization (CS). A questionnaire, the Central Sensitization Inventory (CSI), was recently developed to help clinicians identify patients whose presenting symptoms may be related to central sensitivity syndrome (CSS). The aims of the present study were to examine criterion validity and construct validity of the Japanese version of the CSI (CSI-J), and to investigate prevalence rates of CS severity levels in patients with musculoskeletal disorders. METHODS: Translation of the CSI into Japanese was conducted using a forward-backward method. Two hundred and ninety patients with musculoskeletal pain disorders completed the resultant CSI-J. A subset of the patients (n = 158) completed the CSI-J again one week later. The relationships between CSI and clinical symptoms, EuroQol 5-dimension (EQ-5D) and Brief Pain Inventory (BPI), were examined for criterion validity. EQ-5D assesses Health-related QOL and BPI measures pain intensity and pain interference. The psychometric properties were evaluated with analyses of construct validity, factor structure and internal consistency, and subsequently investigate the prevalence rates of CS severity levels. RESULTS: The CSI-J demonstrated high internal consistency (Cronbach's α = 0.89) and test-retest reliability was excellent value (ICC = 0.85). The CSI-J was significantly correlated with EQ-5D (r = -0.44), pain intensity (r = 0.42), and pain interference (r = 0.48) (p < 0.01 for all). Ten percent of the participants were above the cutoff "40". The exploratory factor analysis resulted in 5-factor model. CONCLUSIONS: This study reported that the CSI-J was a useful and psychometrically sound tool to assess CSS in Japanese patients with musculoskeletal disorders. The finding of the prevalence rates of CS severity levels in patients with musculoskeletal disorders may help clinicians to decide strategy of treatment.