Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

Introduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. Methods: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, "responders" (≥30% reduction in weekly pain at any time point) were identified. Results: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months (F(3,450) = 26.22, P < 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were "responders" but could not be identified by baseline parameters. "Responders" exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious. Conclusion: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.

Wellness of patients with chronic pain is not only about pain intensity.

OBJECTIVE: Attaining good outcomes in the management of chronic pain remains a clinical challenge. This study aimed to investigate the relationships between - and the contribution of - pain and related conditions to the wellness of these patients. DESIGN: A secondary analysis of database of patients with chronic pain treated with medical cannabis (MC) to carry out a one-year prospective follow-up study was conducted. Questionnaires were completed before (T0 ), six (T6 ), and twelve (T12 ) months after MC initiation. Data included patients' demographics and questionnaires related to three latent factors: pain intensity measures, related conditions (catastrophizing, sleep disturbance, anxiety, and depression), and wellness parameters (quality-of-life, disability, subjective-health-state). Weighted average of the observed variables (WOBs) were calculated for each latent factor. Longitudinal structural equation modeling (SEM) and mediation analyses were performed to identify predictors and interrelations between the WOBs, respectively. RESULTS: Participants included 510 patients. All variables were significantly improved from T0 to T6 and T12 . SEM revealed that related conditions, and to a lesser extent pain, predicted wellness at T0 , T6 , and T12 (related conditions: ß0  = 0.55, p < 0.001; ß6  = 0.54, p < 0.001; and ß12  = 0.51, p < 0.001; pain: ß0  = 0.42, p < 0.001; ß6  = 0.18, p < 0.001; and ß12  = 0.25, p < 0.001). Mediation analyses demonstrated that the effect of WOB-related conditions was greater than WOB-pain on wellness. CONCLUSION: Wellness of patients with chronic pain can be determined not only by pain itself but even more so by the severity of related conditions. Thus, considering a broad spectrum of pain measures and related conditions seems relevant for improving the wellness of patients with chronic pain.

Increased functional connectivity between limbic brain areas in healthy individuals with high versus low sensitivity to cold pain: A resting state fMRI study.

BACKGROUND: The representation of variability in sensitivity to pain by differences in neural connectivity patterns and its association with psychological factors needs further investigation. This study assessed differences in resting-state functional connectivity (rsFC) and its association to cognitive-affective aspects of pain in two groups of healthy subjects with low versus high sensitivity to pain (LSP vs. HSP). We hypothesized that HSP will show stronger connectivity in brain regions involved in the affective-motivational processing of pain and that this higher connectivity would be related to negative affective and cognitive evaluations of pain. METHODS: Forty-eight healthy subjects were allocated to two groups according to their tolerability to cold stimulation (cold pressor test, CPT, 1°C). Group LSP (N = 24) reached the cut-off time of 180±0 sec and group HSP tolerated the CPT for an average of 13±4.8 sec. Heat, cold and mechanical evoked pain were measured, as well as pain-catastrophizing (PCS), depression, anxiety and stress (DASS-21). All subjects underwent resting state fMRI. ROI-to-ROI analysis was performed. RESULTS: In comparison to the LSP, the HSP had stronger interhemispheric connectivity of the amygdala (p = 0.01) and between the amygdala and nucleus accumbens (NAc) (p = 0.01). Amygdala connectivity was associated with higher pain catastrophizing in the HSP only (p<0.01). CONCLUSIONS: These findings suggest that high sensitivity to pain may be reflected by neural circuits involved in affective and motivational aspects of pain. To what extent this connectivity within limbic brain structures relates to higher alertness and more profound withdrawal behavior to aversive events needs to be further investigated.

More Insight on the Role of Personality Traits and Sensitivity to Experimental Pain.

PURPOSE: The present study aimed to assess the influence of personality traits on the variability of sensitivity to pain in two distinct groups of healthy subjects with low versus high sensitivity to pain (LSP vs HSP, respectively). METHODS: Healthy subjects (n=156) were allocated to two groups according to their tolerability to cold stimulation (cold pressor test, CPT, 1°C). Group LSP (n=76) reached the cut-off time of 180±0 sec, and a size matched group of HSP (n=80) tolerated the CPT for an average of 10.5±3.4 sec only. Subjects from both groups completed the self-reported pain sensitivity questionnaire (PSQ), the Pain Catastrophizing Scale (PCS), and the Neuroticism Extraversion Openness - Five Factor Inventory (NEO-FFI). RESULTS: In comparison to the LSP group, HSP individuals had higher scores of PSQ (p<0.001), catastrophizing (p=0.001), and extraversion (p=0.01). By adjusting for age and gender, mediation analyses revealed that catastrophizing mediated the relationship between neuroticism and pain sensitivity, both in the allocation of subjects to a certain group of sensitivity to pain (LSP or HSP, B=0.02 95% CI: 0.006-0.040) and in the PSQ score (B=0.01 95% CI: 0.001-0.023). CONCLUSION: These results, which were demonstrated by two different prisms (CPT and PSQ), point to the potential of the five-factor inventory and pain catastrophizing scale as tools for identifying specific personality traits associated with a high sensitivity to pain.

Specific phytocannabinoid compositions are associated with analgesic response and adverse effects in chronic pain patients treated with medical cannabis.

Medical cannabis (MC) treatment for chronic pain is increasing, but evidence regarding short- and long-term efficacy and associated adverse effects (AEs) of the different cannabis plant components is limited. Most reports focus on two phytocannabinoids, (-)-Δ9-trans-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD). This study, aimed to identify patterns of phytocannabinoid compositions associated with MC treatment response and with related AEs. Participants in this multicenter prospective cohort were patients with chronic non-cancer pain that were prescribed MC by physicians. Data was collected before MC treatment, at one month (short-term) and at 12 months (long-term). Simultaneously, liquid chromatography mass spectrometry identification and quantification of phytocannabinoids from the cultivars were performed. The monthly dose of each phytocannabinoid for each patient was z-scaled and clustered into ten groups to assess the difference in analgesic treatment response (≥30%/50% pain intensity reduction) and AEs rates. We identified ten clusters that had similar analgesic treatment response rates. However, there were significant differences in AEs rates both at short- and long-term. We identified specific phytocannabinoid compositions that were associated with overall AEs rates (5% compared to 53% at short-term and 44% at long-term) and with specific AEs rates such as MC related central nervous system, gastrointestinal and psychological AEs. To conclude, Evaluating only Δ9-THC or CBD is insufficient to find associations with MC related AEs. Therefore, comprehensive profiling of phytocannabinoids is needed to discover associations to related AEs and help physicians prescribe safer cannabis with less AEs while still relieving pain.

Additive Analgesic Effect of Transcranial Direct Current Stimulation Together with Mirror Therapy for the Treatment of Phantom Pain.

OBJECTIVE: Current analgesic treatments for phantom pain are not optimal. One well-accepted yet limited nonpharmacological option is mirror therapy, which is thought to counterbalance abnormal plasticity. Transcranial direct current stimulation (tDCS) is an emerging approach believed to affect the membrane potential and activity threshold of cortical neurons. tDCS analgesic effectiveness, however, is mild and short, rendering it a noneffective stand-alone treatment. This study aimed to assess if a combination of mirror therapy with tDCS results in a superior analgesic effect as compared with mirror therapy alone in patients suffering from phantom pain due to recent amputation. DESIGN: Following ethical approval, eligible patients provided informed consent and were randomly assigned to a study treatment group that continued for 2 weeks (once daily): 1) mirror therapy; 2) mirror therapy and sham tDCS; or 3) mirror therapy and tDCS. Assessments were done before treatment; at the end of treatment weeks 1 and 2; and at 1 week, 1 month, and 3 months following treatment. The primary outcome measure was pain intensity. Secondary measures were derived from the Short Form McGill Pain Questionnaire and the Brief Pain Inventory. RESULTS: Thirty patients were recruited, and 29 patients completed the study. Three months following treatment, pain intensity was significantly (P<0.001) reduced in the combined treatment group (reduction of 5.4±3.3 points) compared with the other study arms (mirror therapy, 1.2±1.1; mirror therapy and sham tDCS, 2.7±3.2). All secondary outcome results were in line with these findings. CONCLUSIONS: Combining tDCS with mirror therapy results in a robust long-lasting analgesic effect. These encouraging findings may contribute to the understanding of the underlying mechanisms of phantom pain.

Symptom clusters in hospitalized older adults: Characteristics and outcomes.

Hospital care in medical patients relies mostly on objective measures with limited assessment of subjective symptoms. We subgrouped 331 hospitalized older adults with medical diagnosis (age 75.5 ± 7.1) according to the severity of multiple symptoms to explore if these subgroups differed in health-related characteristics on admission and functional outcomes one month post-discharge. Cluster analysis identified three subgroups based on experiences with five highly distressing symptoms (fatigue, dyspnea, dizziness, sleep disturbance, pain): low levels of all symptoms, high levels of all symptoms; moderate levels of four symptoms with high dyspnea. Belonging in different subgroups was accompanied by different levels of cognitive and mental, but not physical or health status. Patients in the subgroup "Moderate Levels with High Dyspnea" had significantly lower risk of decline in post-discharge instrumental activities of daily living than other subgroups. Better understanding of older hospitalized adults' symptom profiles may yield important information on health condition and recovery.

Medical cannabis treatment for chronic pain: Outcomes and prediction of response.

BACKGROUND: Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, questionnaire-based prospective cohort was aimed to assess the long-term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success. METHODS: Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity). RESULTS: A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12-month follow-up. At 1 year, average pain intensity declined from baseline by 20% [-1.97 points (95%CI = -2.13 to -1.81; p < 0.001)]. All other parameters improved by 10%-30% (p < 0.001). A significant decrease of 42% [reduction of 27 mg; (95%CI = -34.89 to 18.56, p < 0.001)] from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non-serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite. CONCLUSIONS: This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild-to-modest long-term improvement of the tested measures and identifying possible predictors for treatment success.

The relationship between sensitivity to pain and conditioned pain modulation in healthy people.

BACKGROUND: The relationship between sensitivity to pain and conditioned pain modulation (CPM) - a paradigm reflecting the activity of the endogenous descending analgesic system - is still unclear. This study aimed at investigating CPM magnitude in two distinct subgroups of healthy subjects, presenting low vs. high sensitivity to pain (LSP vs. HSP, respectively), by employing two different thermal paradigms of CPM. METHOD: Ninety-five healthy subjects (out of 293 tested) were identified as LSP (n = 48) or HSP (n = 47) according to their tolerance time to noxious cold stimulation (Cold Pressor Test, 1 °C). All subjects were exposed to two different paradigms of CPM: 1) Fixed temperature 'test-pain' (TP) where phasic, fixed painful heat stimuli of 47 °C were administered before and during a prolonged 'conditioning stimulus' (cold water at 12 °C for 30 s); and 2) Individually based 'pain-60' where TP was determined as the temperature that induced pain at a magnitude of 60 on a 0-100 rating scale (with the same conditioning stimulus). RESULT: Using both thermal paradigms, LSP subjects showed decreased CPM magnitudes in comparison to HSP (p < 0.0001 in both paradigms). Within each group, no differences in the magnitudes of CPM were found between the two paradigms. CONCLUSION: These findings show that regardless of the thermal CPM paradigm employed, healthy individuals exhibiting low sensitivity to pain have a low pain inhibition profile and vice-versa. It is suggested that in healthy subjects, pain sensitivity predisposes the magnitude of CPM and not the other way around.

The effects of a dopamine agonist (apomorphine) on experimental and spontaneous pain in patients with chronic radicular pain: A randomized, double-blind, placebo-controlled, cross-over study.

BACKGROUND: Although evidence suggests that dopaminergic systems are involved in pain processing, the effects of dopaminergic interventions on pain remains questionable. This randomized, double blinded, placebo-controlled, cross-over study was aimed at exploring the effect of the dopamine agonist apomorphine on experimental pain evoked by cold stimulation and on spontaneous pain in patients with lumbar radicular (neuropathic) pain. METHODS: Data was collected from 35 patients with chronic lumbar radiculopathy (18 men, mean age 56.2±13 years). The following parameters were evaluated before (baseline) and 30, 75 and 120 minutes subsequent to a subcutaneous injection of 1.5 mg apomorphine or placebo: cold pain threshold and tolerance in the painful site (ice pack, affected leg) and in a remote non-painful site (12°C water bath, hand), and spontaneous (affected leg) pain intensity (NPS, 0-100). RESULTS: One-hundred and twenty minutes following apomorphine (but not placebo) injection, cold pain threshold and tolerance in the hand increased significantly compared to baseline (from a median of 8.0 seconds (IQR = 5.0) to 10 seconds (IQR = 9.0), p = 0.001 and from a median of 19.5 seconds (IQR = 30.2) to 27.0 seconds (IQR = 37.5), p<0.001, respectively). In addition, apomorphine prolonged cold pain tolerance but not threshold in the painful site (from a median of 43.0 seconds (IQR = 63.0) at baseline to 51.0 seconds (IQR = 78.0) at 120 min, p = 0.02). Apomorphine demonstrated no superiority over placebo in reducing spontaneous pain intensity. CONCLUSION: These findings are in line with previous results in healthy subjects, showing that apomorphine increases the ability to tolerate cold pain and therefore suggesting that dopaminergic interventions can have potential clinical relevance.

Does self-perception of sensitivity to pain correlate with actual sensitivity to experimental pain?

BACKGROUND: People often state that they are "sensitive" or "insensitive" to pain. However, the accuracy and clinical relevance of such statements is unclear. OBJECTIVE: The aim of this study was to search for associations between self-perception of sensitivity to pain and experimental pain measures, including known psychophysical inhibitory or excitatory pain paradigms. SUBJECTS AND METHODS: Subjective sensitivity to pain was reported by 75 healthy participants and included three self-perceived variables: pain threshold, pain sensitivity and pain intensity in response to a hypothetical painful event (hypothetical pain intensity [HPI]). Experimental pain measures consisted of thermal pain threshold (°C), suprathreshold thermal pain intensity (Visual Analog Scale, 0-100) and the psychophysical paradigms of conditioned pain modulation (CPM) and temporal summation (TS), representing inhibitory and excitatory pain processes, respectively. RESULTS: No significant correlations were found between self-perceived pain threshold or pain sensitivity and any of the experimental pain measures. In contrast, the reported HPI correlated with thermal pain threshold (r = -0.282; p = 0.014), suprathreshold thermal pain intensity (r = 0.367; p = 0.001) and CPM (r = 0.233; p = 0.044), but not with TS. CONCLUSION: Self-perception of pain sensitivity articulated by intangible expressions such as pain threshold or pain sensitivity is unrelated to actual sensitivity to experimental pain. In contrast, when measured by intensity of a hypothetical painful event (HPI), sensitivity to pain is associated with some, but not all, experimental pain reports. Further studies are needed for better understanding of these associations and their potential clinical significance.

Double whammy: Adverse childhood events and pain reflect symptomology and quality of life in women in substance abuse treatment.

BACKGROUND: This study examined the profiles of symptoms and health-related quality of life (QOL) of women in substance abuse treatment, comparing those with higher versus lower histories of adverse childhood events (ACE), and those with versus without current pain. METHODS: Adult women in outpatient substance abuse treatment (n = 30) completed questionnaires (cross-sectional study) on topics including drug use, adverse childhood events (ACE), QOL, functional ability, current pain, and depression. RESULTS: Women with pain indicated significant differences in emotional (p < 0.05), and functional ability (p < 0.01); but no significant differences were found between women with high versus low levels of ACE. Yet, radar plots of women with both current pain and high levels of ACE, versus those without, portrayed a distinctive profile indicating high levels of anxiety and depression. CONCLUSIONS: Rather than a checklist, visual composites of symptoms experienced by women in substance abuse treatment illustrates areas of concern in the overall status of women in substance abuse treatment.

Methylphenidate attenuates the response to cold pain but not to aversive auditory stimuli in healthy human: a double-blind randomized controlled study.

INTRODUCTION: We recently showed that the psycho-stimulant norepinephrine-dopamine reuptake inhibitor methylphenidate (MP) prolonged cold pain threshold and tolerance in adults with attention-deficit hyperactivity disorder (ADHD). OBJECTIVES: The objectives of the present study were to: (1) examine whether MP has antinociceptive properties in healthy men; (2) test MP's effects on responses to aversive auditory stimuli. The underlying aim was to determine whether MP exerts antinociceptive properties or more generalized, nonspecific attenuating effects on different aversive sensory modalities. METHODS: This double-blind, crossover, randomized placebo-controlled study consisted of 2 sessions one week apart from each other. In each session, pain threshold (seconds) and tolerance (seconds) in response to painful cold stimulation were measured. Additionally, threshold (dB) and tolerance (seconds) to loud aversive auditory stimuli (500 Hz, 2000 Hz and white noise) were also tested prior to and 2 hours following the administration of a single dose of either 20 mg MP or an identical looking placebo. RESULTS: Forty men, 26.1 ± 4.0 (mean ± SD) years were enrolled in the study. Wilcoxon signed-rank test analyses showed that MP, but not the placebo, produced a significant increase in cold pain threshold (from 4.1 ± 2.6 to 5.4 ± 3.1 seconds, P = 0.001 and from 4.5 ± 2.6 to 4.3 ± 2.7 seconds, P = 0.2, respectively) and tolerance (from 57.8 ± 54.0 to 73.8 ± 61.8 seconds, P = 0.001 and from 52.5 ± 53.7 sec to 57.0 ± 52.9 seconds, P = 0.1, respectively). No significant changes were found in any of the auditory parameters. CONCLUSION: These results suggest that MP has an effect on nociceptive pathways rather than a nonspecific, generalized attenuating effect on aversive sensory stimuli.

Clinical analgesia correlates with decline in temporal summation in response to remifentanil infusion in patients with chronic neuropathic (radicular) pain.

BACKGROUND: Animal studies have shown that in addition to their antinociceptive effects, opioids have attenuated the electrophysiological "wind-up" phenomenon. Although effects of opioids on clinical pain and on temporal summation (TS), the human correlatives of this phenomenon, have been tested repeatedly, correlations between these two parameters have not been reported so far. OBJECTIVES: To search for possible correlations between the effects of remifentanil on clinical pain intensity and on the magnitude of TS in patients with chronic pain. DESIGN: A single-blinded prospective study. SETTING: A tertiary care pain clinic. PATIENTS: Thirty-one patients (24 men) with chronic lumbar (radicular) neuropathic pain. INTERVENTION: Intervenous administration of saline followed by remifentanil infusions. MAIN OUTCOME MEASURES: Clinical pain intensity and thermal TS measured at baseline, during infusion of each drug and 20 minutes after termination of remifentnail infusion. RESULTS: Friedman test revealed statistically significant differences in the magnitudes of both clinical pain intensity and TS (x(2(3)) = 73, p < 0.001 and x(2(3)) = 11.38, p = 0.01, respectively). Post hoc analysis (Wilcoxon signed-rank test) showed significant differences between clinical pain intensities measured at all time points but significant reductions in the magnitudes of TS were found only during remifentanil compared to baseline (p = 0.014) and to saline (p = 0.019). The difference in clinical pain between saline and remifentanil positively correlated with the difference in TS measured at the same time points (Spearman's test; r = 0.444, p = 0.012). CONCLUSIONS: These results point to a possible causative relationship between TS and opioid analgesia.

Individually based measurement of temporal summation evoked by a noxious tonic heat paradigm.

BACKGROUND: A model for measuring temporal summation (TS) by tonic noxious stimulation was recently proposed. However, methodological variations between studies make it difficult to reach a consensus regarding the way TS should be applied and calculated. The present study aimed to present a calculation method of TS magnitude produced by a tonic heat model in a large cohort of healthy subjects. METHODS: Noxious heat stimulation (46.5°C/2 minutes) was applied to the forearm of 154 subjects who continuously rated pain intensity using a computerized visual analog scale. TS was calculated by "mean group" and "individual" approaches. RESULTS: A "typical" pattern of pain response, characterized by a peak pain followed by a decrease in intensity to a nadir and subsequently a progressive increase in pain scores, was exhibited by 86.4% of the subjects. Using the "mean group" and "individual" calculation approaches, the mean ± standard deviation magnitudes of TS were 31.4±27.5 and 41.0±26.0, respectively (P<0.001). Additionally, using the individualized approach, we identified a different ("atypical") response pattern among the rest of the subjects (13.6%). CONCLUSION: The results support the tonic heat model of TS for future utilization. The individualized TS calculation method seems advantageous since it better reflects individual magnitudes of TS.

Experimental comparison of parametric versus nonparametric analyses of data from the cold pressor test.

UNLABELLED: Parametric statistical methods are common in human pain research. They require normally distributed data, but this assumption is rarely tested. The current study analyzes the appropriateness of parametric testing for outcomes from the cold pressor test (CPT), a common human experimental pain test. We systematically reviewed published CPT studies to quantify how often researchers test for normality and how often they use parametric versus nonparametric tests. We then measured the normality of CPT data from 7 independent small to medium cohorts and 1 study of >10,000 subjects. We then examined the ability of 2 common mathematical transformations to normalize our skewed data sets. Lastly, we performed Monte Carlo simulations on a representative data set to compare the statistical power of the parametric t-test versus the nonparametric Wilcoxon Mann-Whitney test. We found that only 39% of published CPT studies (47/122) mentioned checking data distribution, yet 72% (88/122) used parametric statistics. Furthermore, among our 8 data sets, CPT outcomes were virtually always nonnormally distributed, and mathematical transformations were largely ineffective in normalizing them. The simulations demonstrated that the nonparametric Wilcoxon Mann-Whitney test had greater statistical power than the parametric t-test for all scenarios tested: For small effect sizes, the Wilcoxon Mann-Whitney test had up to 300% more power. PERSPECTIVE: These results demonstrate that parametric analyses of CPT data are routine but incorrect and that they likely increase the chances of failing to detect significant between-group differences. They suggest that nonparametric analyses become standard for CPT studies and that assumptions of normality be routinely tested for other types of pain outcomes as well.

The psychometric properties of the Hebrew version of the Memorial Symptom Assessment scale (MSAS-Heb) in patients with breast cancer.

CONTEXT: To date, no report of the psychometric properties of the Hebrew version of the Memorial Symptom Assessment Scale (MSAS-Heb) has been available, which may be a barrier to comprehensively assessing symptom frequency, severity, and distress in Israeli patients with cancer. OBJECTIVES: This study aimed to translate the MSAS into Hebrew and to evaluate the psychometric properties in Israeli patients with cancer. METHODS: The original 32-item MSAS was translated into Hebrew using the forward and backward procedure, and administered to female patients with early stage breast cancer (stages I-IIIA) who had received adjuvant chemotherapy. In addition, patients completed a demographic questionnaire, the Lee Fatigue Scale, the Center for Epidemiological Studies-Depression Scale, the General Sleep Disturbance Scale, a numeric rating scale for pain intensity, the Multidimensional Quality of Life Scale-Cancer and the Karnofsky Performance Status Scale. RESULTS: A sample of 110 patients was recruited (mean age 45.5 ± 10.1 years). The most frequent symptoms were hair loss (96.4%), lack of energy (88.2%) and "I do not look like myself" (80.9%), and the most infrequent were vomiting (7.3%), problems with urination (10.9%), and shortness of breath (20.9%). Cronbach alpha coefficients for the MSAS-Heb subscales (i.e., physical, psychological and global distress index) ranged from 0.78 to 0.90. All MSAS-Heb subscales and all the other questionnaires used in this study were significantly correlated (P < 0.0001), with expected directions. CONCLUSION: The MSAS-Heb is a valid and a reliable measure and should be a useful tool in the clinical arena and in future studies for evaluation of multiple symptoms in Israeli patients with cancer.