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.

[SMALL FIBER POLYNEUROPATHY IN YOUNG PATIENTS].

INTRODUCTION: Small fiber polyneuropathy (SFPN) is associated with a variety of clinical conditions. Common to these conditions is the deviation from healthy physiological homeostatic balance, which hinders small fiber neurons viability, resulting in their damage. The most common cause for SFPN in the western world is diabetes, followed by a long list of other risk-factors, some are age-related. Accumulating evidence suggests that in young patients a leading cause (up-to 50% of cases) is autoimmune-related. A variety of symptoms can be seen in SFPN. Commonly, first to appear are sensory symptoms in the extremities. Autonomic symptoms can then join, or even be the presenting symptoms. This sensory-autonomic combination can have a dramatic mal-effect on the patient's quality of life. Diagnosis is based primarily on skin biopsy and/or Autonomic-Functional-Testing. Often, in cases where no etiology is identified, EMG is normal and the skin biopsy/autonomic testing is not performed, clinicians tend to incorrectly diagnose a non-organic situation. Correct and preferably early diagnosis is of essence since peripheral fibers can recover if the disease pathophysiological factor is removed, leading to less suffering and improved quality of life of patients.

Automated Mechanical Repositioning Treatment for Posterior Canal Benign Paroxysmal Positional Vertigo: A Single-Center Experience and Literature Review.

OBJECTIVE: To evaluate the feasibility and effectiveness of automated mechanical repositioning treatment (AMRT) for posterior canal benign paroxysmal positional vertigo -(PC-BPPV). PATIENTS AND METHODS: We reviewed all PC-BPPV patients admitted to our department between January and -December 2016. The inclusion criteria mainly required conducting a diagnosis for PC-BPPV by using the Dix-Hallpike test, a PC-BPPV history within 1 month, no intake of medications for the last 48 h. Compared with the cases who received classical manual repositioning treatment (CMRT), the proportion of patients who underwent AMRT with a resolution within the 1-week follow-up session after initial treatment and a recurrence during the 6-month follow-up were evaluated. RESULTS: A total of182 patients who underwent AMRT and 152 patients who underwent CMRT were included. Compared with the CMRT group, the AMRT group had a higher rate of complete or partial resolution and positional nystagmus at the 1 week follow-up (92.6 vs. 86.2%; p = 0.004). AMRT with less treatment cycles was more effective than CMRT (1.5 vs. 1.9; p < 0.001). After 6 months of follow-up, the cumulative recurrence rate of the AMRT group was significantly lower than that of the CMRT group (3.0 vs. 8.9%; p = 0.037). CONCLUSION: AMRT is a feasible and effective procedure for the resolution of PC-BPPV.

Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®).

BACKGROUND AND OBJECTIVES: Inappropriate use of analgesic drugs has become increasingly pervasive over the past decade. Currently, drug abuse potential is primarily assessed post-marketing; no validated tools are available to assess this potential in phase II and III clinical trials. This paper describes the development and feasibility testing of a Misuse, Abuse, and Diversion Drug Event Reporting System (MADDERS), which aims to identify potentially abuse-related events and classify them according to a recently developed classification scheme, allowing the quantification of these events in clinical trials. METHODS: The system was initially conceived and designed with input from experts and patients, followed by field-testing to assess its feasibility and content validity in both completed and ongoing clinical trials. RESULTS: The results suggest that MADDERS is a feasible system with initial validity. It showed higher rates of the triggering events in subjects taking medications with known abuse potential than in patients taking medications without abuse potential. Additionally, experts agreed on the classification of most abuse-related events in MADDERS. DISCUSSION AND CONCLUSIONS: MADDERS is a new systematic approach to collect information on potentially abuse-related events in clinical trials and classify them. The system has demonstrated feasibility for implementation. Additional research is ongoing to further evaluate its validity. SCIENTIFIC SIGNIFICANCE: Currently, there are no validated tools to assess drug abuse potential during clinical trials. Because of its ease of implementation, its systematic approach, and its preliminary validation results, MADDERS could provide such a tool for clinical trials. (Am J Addict 2016;25:641-651).

The effect of hydromorphone therapy on psychophysical measurements of the descending inhibitory pain systems in patients with chronic radicular pain.

OBJECTIVE: Conditioned pain modulation (CPM) and offset analgesia (OA) are considered to represent paradigms of descending inhibitory pain modulation in humans. This study tested the effects of hydromorphone therapy on descending inhibitory pain modulation, as measured by changes from baseline in the magnitudes of CPM and OA. DESIGN: Prospective evaluation. SETTING: Institute of Pain Medicine, Rambam Health Care Campus. SUBJECTS: Patients with chronic radicular pain. METHODS: Thirty patients received 4 weeks of oral hydromorphone treatment at an individually titrated dose (mean ± standard deviation dose of 11.6 ± 4.8 mg/day). CPM and OA were assessed before and after hydromorphone treatment. CPM was assessed by subtracting the response to a painful phasic heat stimulus administered simultaneously with a conditioning cold pain stimulus, from the response to the same heat stimulus administered alone. The OA paradigm consisted of a three-temperature stimuli train (T1 = 49°C [5 seconds], T2 = 50°C [5 seconds], and T3 = 49°C [20 seconds]). The magnitude of OA was quantified by subtracting minimal pain scores obtained during T3 from the maximal pain scores obtained during T2. RESULTS: CPM scores changed from a baseline of 17.7 ± 20.6 to 21 ± 20.4 following treatment, and OA scores changed from 7.8 ± 20.5 to 9.7 ± 14.6. Wilcoxon signed rank test indicated that these changes were not significant (CPM: P = 0.22; OA: P = 0.44). McNemar test revealed that the percentage of patients who exhibited a change in the direction of CPM or OA in response to hydromorphone treatment was not significant (CPM: P = 0.37; OA: P = 0.48). CONCLUSIONS: These results suggest that the descending inhibitory pain modulation, as manifested in humans by CPM and OA, is unlikely to be mediated by hydromorphone therapy.

Alterations in pain response are partially reversed by methylphenidate (Ritalin) in adults with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by dysregulation of sensory processing and neurobiology of dopamine. Although cumulative evidence suggests that dopamine is involved in pain processing, pain perception in ADHD subjects and the effect of dopamine agonists such as methylphenidate (MP, Ritalin) on it have rarely been studied. AIMS: The aims of this study were to (1) psychophysically assess sensitivity to pain in ADHD subjects as compared to controls and (2) examine the effects of MP on pain response in ADHD subjects. METHODS: Thirty subjects with ADHD and 30 age- and gender-matched controls participated in a preliminary trial. Pain threshold, intensity, and tolerance in response to cold pain stimulation were measured for both groups (ADHD with no treatment). In addition, the ADHD group was reassessed following a single dose of MP treatment. RESULTS: The ADHD subjects "without MP" in comparison with controls displayed significantly shorter cold pain threshold (2.8 ± 2.1 vs. 5.8 ± 2.5 seconds, respectively, P < 0.001) and cold tolerance (21.8 ± 22.3 vs. 62.8 ± 59.8 seconds, respectively P < 0.001). No differences in pain intensities between the groups were found. Following MP treatment, both cold threshold and tolerance in the ADHD subjects increased significantly compared to those with no treatment (3.6 ± 2.5 seconds, P = 0.011, and 46.4 ± 53.3 seconds, P < 0.001, respectively). CONCLUSIONS: These results suggest that adults with ADHD are more sensitive to pain compared with controls and that MP may exert antinociceptive properties in these subjects. Randomized, controlled trials are warranted to verify these findings.

Test-retest and interrater reliability of experimental within-subject variability of pain reports as assessed by the focused analgesia selection test.

Introduction: Within-subject variability (WSV) of pain intensity reports has been shown to predict the placebo response. The focused analgesia selection test (FAST), which allows to experimentally assess WSV of pain reports, has been used as a screening tool to identify participants who are likely to have a strong placebo response in drug-development clinical trials. Yet, the reliability of FAST has not been reported. Objectives: To assess test-retest and interrater reliability of the FAST outcomes. To mimic pharma-sponsored clinical trials, we enlisted inexperienced assessors who underwent limited training. Methods: Healthy volunteers performed the FAST twice within a week and were randomly assigned to either the test-retest group or the interrater group. T-tests, partial Pearson correlations, intraclass correlations (ICC), and Bland-Altman plots were generated to assess FAST outcomes' reliability. Results: Sixty-three participants completed the study and were assigned to the test-retest (N = 33) or interrater (N = 30) arms. No statistically significant differences in the FAST outcomes were detected between the 2 sessions, except for the FAST covariance (FAST CoV) in the interrater assessment (P = 0.009). Test-retest reliabilities of the FAST-main outcomes were r = 0.461, ICC = 0.385 for the FAST R 2 and r = 0.605, ICC = 0.539 for the FAST ICC and in the interrater cohort, they were FAST R 2: r = 0.321, ICC = 0.337 and FAST ICC: r = 0.355, ICC = 0.330. Conclusion: Using inexperienced assessors, the FAST outcomes test-retest ranged from moderate to strong, whereas the interrater reliability ranged from weak to poor. These results highlight the importance of adequately training study staff members before using this tool in multicentre clinical trials.

Anti tumor necrosis factor - alpha adalimumab for complex regional pain syndrome type 1 (CRPS-I): a case series.

BACKGROUND AND AIMS: Evidence suggests tumor necrosis factor-alpha (TNF-α) mediates, at least in part, symptoms and signs in complex regional pain syndrome (CRPS). Here, we present a case series of patients with CRPS type 1, in whom the response to the anti-TNF-α adalimumab was assessed. METHODS: Ten patients with CRPS type 1 were recruited. Assessments were performed before treatment, at 1 week, and 1, 3, and 6 months following 3 biweekly subcutaneous injections (40 mg/0.8 mL) adalimumab (Humira(®) ) and included the followings: Pain intensity using a 0-10 cm visual analog scale; the Short Form of the McGill Pain Questionnaire; the Beck Depression Inventory; the SF-36 questionnaire and mechanical and thermal thresholds (Von frey hair and Thermal Sensory Analyzer, respectively). In addition to the description of individual patient responses, both intention to treat (ITT) and per-protocol (PP) analyses were performed for the entire group. RESULTS: Three subgroups of patients were identified (3 patients in each): "nonresponders", "partial responders", and "robust responders" in whom improvement in almost all parameters was noted. Both the ITT and PP analyses demonstrated only a trend toward improvement in mechanical pain thresholds following treatment (ITT χ² = 13.83, P = 0.008; PP χ² = 10.29, P = 0.036). CONCLUSION: These results suggest adalimumab, and possibly other anti-TNF-α, can be potentially useful in some (although not in all) patients with CRPS type 1. These preliminary results along with the growing body of evidence which points to the involvement of TNF-α in the pathogenesis of CRPS justify further studies in this area.

Time since onset might be of essence: A recommendation to assess the effects of combination of non-pharmacological neuromodulatory approaches at early stage since symptoms onset.

In the past decade researchers began to assess the potential beneficial effects of non-invasive brain stimulation (NIBS) combined with a behavioral task as a treatment approach for various medical conditions. Transcranial direct current stimulation (tDCS) applied to the motor cortex combined with another treatment approach has been assessed as analgesic treatment in neuropathic and non-neuropathic pain conditions, and was found to exert only modest pain relief. Our group results show that combined tDCS and mirror therapy dramatically reduced acute phantom limb pain intensity with long-lasting effects, potentially preventing pain chronification. A review of the scientific literature indicates that our approach differs from that of others: We applied the intervention at the acute stage of the disease, whereas other studies applied the intervention in patients whose disease had already been established. We suggest that the timing of administration of the combined intervention is critical. Unlike in patients with chronic painful condition, in which the maladaptive plasticity associated with pain chronification and chronicity is well-consolidated, early treatment at the acute pain stage may be more successful in counterbalancing the not-yet consolidated maladaptive plasticity. We encourage the research community to test our hypothesis, both in the treatment of pain, and beyond.

Correlations between within-subject variability of pain intensity reports and rubber hand illusion proprioceptive drift.

INTRODUCTION: Consistent with the Bayesian brain hypothesis, the within-subject variability of pain intensity reports as captured with the Focused Analgesia Selection Test (FAST) might be a surrogate measure of the certainty in ascending noxious signals. The outcomes of a non-pain-related task, the rubber hand illusion, were hypothesized to reflect the same construct. This study aimed to explore whether within-subject differences in variability of pain intensity reports and the outcomes of the rubber hand illusion might be related. METHODS: Nonclinical participants underwent the classic rubber hand illusion under synchronous (experimental) and asynchronous (control) conditions. Two outcomes were assessed: proprioceptive drift and feeling of ownership. Thereafter, participants underwent the FAST to assess the within-subject variability of pain reports in response to heat stimuli. Intraclass correlation (ICC) and the correlation coefficient (R2) were the main outcomes. Spearman's correlations were used to assess associations between the outcomes of the 2 tasks. RESULTS: Thirty-six volunteers completed the study. Both FAST outcomes-ICC (Spearman's r = 0.355, p = 0.033) and R2 (Spearman's r = 0.349, p = 0.037)-were positively correlated with proprioceptive drift in the synchronous but not asynchronous conditions (p > 0.05). The subjective feeling of ownership and FAST outcomes did not correlate (p > 0.05). CONCLUSIONS: The associations between the 2 tasks' outcomes imply that both tasks at least partly assess similar constructs. Current knowledge suggests that this construct represents the person's certainty in perceiving ascending sensory signals, or, in Bayesian terminology, the certainty of the likelihood.

Low Back Pain Patients' Perceptions Regarding Their Own Radiology Reports: Pre-Intervention Survey.

Purpose: While advanced medical technology and unlimited access to medical information might benefit and empower patients, these same advantages may pose some risks, especially in the cases where patients have direct access to advanced imaging studies. The aim of this work was to evaluate three domains related to patients with lower back pain: the patients' perceptions, misconceptions and the experience of anxiety-related symptoms following direct access to their thoraco-lumbar spine radiology report. An additional aim was the assessment of possible associations with catastrophization. Patients and Methods: Patients who were referred to the spine clinic, following the completion of a CT or MRI of their thoraco-lumbar spine were surveyed. Patient perceptions of the importance of having direct access to their imaging report and of the concern they attribute to the medical terms found in their report were evaluated using a set of questionnaires. The medical terms severity scores were then correlated to a reference clinical score created for the same medical terms by spine surgeons. Lastly, patients' anxiety-related symptoms and Pain Catastrophizing Scale (PCS) after reading their radiology report were evaluated. Results: Data from 162 participants (44.6% female), with mean age of 53.1 ± 15.6 years, were collected. Sixty-three percent of the patients stated that reading their report helped them gain better understanding of their medical condition and 84% agreed that having early access to the report helped improve communication with the physician. Patients' degree of concern associated with the medical terms in their imaging report ranged between 2.07 and 3.75, on a scale of 1-5. The patient's degree of concerns were significantly higher for six common medical terms and significantly lower in one, when compared to experts' opinions. A mean (± SD) of 2.86±2.79 anxiety-related symptoms was reported. The mean Pain Catastrophizing Scale (PSC) score was 29.18 ±11.86, ranging from 2 to 52. Both the degree of concerns and the number of symptoms reported were significantly associated with the PCS. Conclusion: Direct access to radiology reports might provoke anxiety symptoms, especially in patients with a tendency for catastrophic thinking. Increasing awareness amongst spine clinicians and radiologist about possible risks associated with direct access to radiology reports could contribute to preventing patients' misconceptions and unnecessary anxiety-related symptoms.

Agreement between children's, nurses' and parents' pain intensity reports is stronger before than after analgesic consumption: Results from a post-operative study.

BACKGROUND: Included in their extensive duties caring for hospitalized children, nurses are the frontline for pain assessment and treatment. Research has found that when nurses' assessments are compared with independent reports by the children or their parents, there are often differences. However, no studies have considered the contribution of analgesic medication consumption to this difference. OBJECTIVES: The aim of this study, was to assess the concordance between the pain scores recorded independently by nurses, children, and their parents both before and 1 h after analgesic consumption. DESIGN/SETTING: The trial was registered at ClinicalTrials.gov (NCT04306679) and was conducted in a post-operative inpatient facility. Following surgery, at first request of analgesic, the clinical nurses recorded the child's pain, as part of routine clinical practice. Within 10 min, the child recorded their pain level in a pain diary. At the same time, the parents separately reported their assessment of their child's pain. This process was repeated again 1 h later, when the nurses, as part of the clinical routine, recorded the children's level of post-medication pain. PARTICIPANTS: Forty-seven children ages 8-17 hospitalized for elective surgery in the General Pediatric Surgery, Orthopedics, Ear-Nose-Throat (ENT), and Oral and Maxillofacial (OM) Departments, and their parents, were included in the current report. RESULTS: The mean pain scores reported by the children were significantly higher than those reported by the nurses, both before (5.77±2.51 vs. 3.90±3.12 [mean ±SD], p <0.001) and 1 h after (3.37±2.48 vs. 0.92±2.08, p <0.001) analgesic consumption. No significant differences were found either before or after analgesic consumption in the NPS reported by the child and parent. Agreement between the NPS scores reported by the child and nurses was good before (ICC = 0.754, p <0.001) and only moderate 1 h after (ICC = 0.504, p = 0.017) analgesic consumption. Similarly, agreement between the NPS scores reported by the child and parents was good before (ICC = 0.855, p <0.001) and only moderate 1 h after (ICC = 0.722, p <0.001) analgesic consumption. CONCLUSIONS: While self-report measures remain the gold standard for pediatric pain care, the results of this study suggest that after analgesic administration, agreement between children's and nurses' assessments, and between children's and parents' assessments of pain deteriorated. Our results further confirm that proxy assessments recorded by parents are closer to their children's assessments than are those of nurses and should consequently be preferred especially after analgesic consumption.

Relations between short-term memory and the within-subject variability of experimental pain intensity reports: Results from healthy and Fibromyalgia patients.

While factors contributing to between-subjects differences in pain have been studied extensively, factors contributing to the within-subjects variability of pain reports are yet unexplored. The aim of this investigation was to assess possible associations between short-term memory and the within-subjects variability of pain reports in healthy and chronic pain patients. Healthy participants were recruited at the University of Haifa, Israel, and Fibromyalgia patients were recruited at a rheumatology department in a central hospital in Lisbon, Portugal. Following consent, both cohorts underwent the same procedures, including the digit-span test, assessing short-term memory, and the FAST procedure, assessing within-subject variability of pain intensity reports in response to experimental pain. One-hundred twenty-one healthy volunteers and 29 Fibromyalgia patients completed the study. While a significant correlation was found between the within-subjects variability and the total score of the short-term memory task (Spearman's r = 0.394, P = 0.046) in the Fibromyalgia group, a marginal correlation emerged in the healthy cohort (r = 0.174, P = 0.056). A possible interpretation of these results is that in the patients' group, at least some of the within-subjects variability of pain intensity reports might be due to error measurement derived by poorer short-term memory, rather than true fluctuations in perception.

Temporal Summation Predicts De Novo Contralateral Pain After Cordotomy in Patients With Refractory Cancer Pain.

BACKGROUND: Percutaneous cervical cordotomy (PCC), which selectively interrupts ascending nociceptive pathways in the spinal cord, can mitigate severe refractory cancer pain. It has an impressive success rate, with most patients emerging pain-free. Aside from the usual complications of neurosurgical procedures, the risks of PCC include development of contralateral pain, which is less understood. OBJECTIVE: To evaluate whether sensory and pain sensitivity, as measured by quantitative sensory testing (QST), are associated with PCC clinical outcomes. METHODS: Fourteen palliative care cancer patients with severe chronic refractory pain limited mainly to one side of the body underwent comprehensive quantitative sensory testing assessment pre-PPC and post-PCC. They were also queried about maximal pain during the 24 h precordotomy (0-10 numerical pain scale). RESULTS: All 14 patients reported reduced pain postcordotomy, with 7 reporting complete resolution. Four patients reported de novo contralateral pain. Reduced sensitivity in sensory and pain thresholds to heat and mechanical stimuli was recorded on the operated side (P = .028). Sensitivity to mechanical pressure increased on the unaffected side (P = .023), whereas other sensory thresholds were unchanged. The presurgical temporal summation values predicted postoperative contralateral pain (r = 0.582, P = .037). CONCLUSION: The development of contralateral pain in patients postcordotomy for cancer pain might be due to central sensitization. Temporal summation could serve as a potential screening tool to identify those who are most likely at risk to develop contralateral pain. Analysis of PCC affords a unique opportunity to investigate how a specific lesion to the nociceptive system affects pain processes.

Effects of Pain-Reporting Education Program on Children's Pain Reports-Results From a Randomized Controlled Post-operative Pediatric Pain Trial.

Objective: Accurate assessment of patients' pain is an essential part of adequate analgesic treatment. Although reporting pain is a complex task, limited-to-no instructions are provided to pediatric patients regarding this process. Our goal in this randomized parallel-group clinical trial (Clinicaltrial.gov study protocol number NCT04306679) was to evaluate if a training program designed to improve children's ability to understand and use pain scales in a post-surgical setting would affect their pain scores. Methods: Eligible children (aged 8-17), hospitalized for elective surgery and their parents were randomized into two groups. Pre-surgery the intervention group underwent a multi-media program aimed to teach and train how to report pain. The control group received standard pre-surgical instructions. Post-surgery, the children reported their pain on 4 pain scales. The primary outcome was the concordance between children's pain intensity scores reported on four pain scales, both in terms of within-child standard deviation and absolute difference. Results: Ninety-six children met inclusion criteria and completed the study. The trained subjects' pain reports had significantly (p = 0.002) lower within-subject standard deviation (0.41 ± 0.31) than the control group (0.67 ± 0.46). In line, regarding absolute difference, the concordance of children's pain reports was twice better in the trained group (mean difference of 0.43 ± 0.40) than in the control group (0.88 ± 0.70) (p < 0.001). Discussion: Our results suggests that children's ability to report pain is a skill that can be improved. Future studies should test the potential clinical impacts of educational interventions aimed to improve pain assessment in children and adults.

En Pointe: Dancers Report Their Pain Less Variably Than Do Controls.

The subjective nature of pain and the lack of a gold standard for objective measurement hinders effective assessment, diagnosis, and treatment. Some individuals, such as professional dancers, are better in assessing and reporting bodily sensations. This observational study aimed to assess whether dancers report their pain less variably, than other people do. After consenting, subjects completed the focused analgesia selection test (FAST), which assesses subjects' variability of pain reports. FAST outcomes, ICC and R2 reflect the magnitude of variability of pain reports observed. In addition, subjects underwent a taste task, which similarly assesses variability of tastes (salty and sweet) intensity reports and completed the Multidimensional Assessment of Interoceptive Awareness questionnaire. Thirty-three professional dancers and 33 healthy aged-matched controls were recruited. The dancers exhibited less variability of pain reports then controls (P = .013), but not in case of tastes-reports. Years of practice was positively correlated with pain reporting variability (r = .447, P = .009, and r = .380, P = .029; for FAST ICC and R2, respectively). Multidimensional Assessment of Interoceptive Awareness subscores correlated with pain reporting variability: R2 and ICC with emotional awareness (r = .260, P = .040, and r = .274, P = .030, respectively), and R2 with trusting [r = .254, P = .044]). PERSPECTIVE: The difference between dancers and controls in the magnitude of variability of pain reports is probably due to the dancers' extensive training, which focuses on attention to body signals. Our results suggest that training can improve subjective pain reports, which are essential for quality clinical care.

Idiopathic distal sensory polyneuropathy: ACTTION diagnostic criteria.

OBJECTIVE: To present standardized diagnostic criteria for idiopathic distal sensory polyneuropathy (iDSP) and its subtypes: idiopathic mixed fiber sensory neuropathy (iMFN), idiopathic small fiber sensory neuropathy (iSFN), and idiopathic large fiber sensory neuropathy (iLFN) for use in research. METHODS: The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the Food and Drug Administration convened a meeting to develop consensus diagnostic criteria for iMFN, iSFN, and iLFN. After background presentations, a collaborative, iterative approach was used to develop expert consensus for new criteria. RESULTS: An iDSP diagnosis requires at least 1 small fiber (SF) or large fiber (LF) symptom, at least 1 SF or LF sign, abnormalities in sensory nerve conduction studies (NCS) or distal intraepidermal nerve fiber density (IENFD), and exclusion of known etiologies. An iMFN diagnosis requires that at least 1 of the above clinical features is SF and 1 clinical feature is LF with abnormalities in sensory NCS or IENFD. Diagnostic criteria for iSFN require at least 1 SF symptom and at least 1 SF sign with abnormal IENFD, normal sensory NCS, and the absence of LF symptoms and signs. Diagnostic criteria for iLFN require at least 1 LF symptom and at least 1 LF sign with normal IENFD, abnormal sensory NCS, and absence of SF symptoms and signs. CONCLUSION: Adoption of these standardized diagnostic criteria will advance research and clinical trials and spur development of novel therapies for iDSPs.

No Relationships Between the Within-Subjects' Variability of Pain Intensity Reports and Variability of Other Bodily Sensations Reports.

PURPOSE: The subjective nature of pain assessment and its large variance negatively affect patient-health care provider communication and reduce the assay sensitivity of pain clinical trials. Given the lack of an objective gold standard measure, identifying the source (true or error) of the within-subject variability of pain reports is a challenge. By assessing the within-subjects variability of pain and taste reports, alongside with interoceptive measures, the current study is aimed to investigate if the ability to reliably report bodily sensations is a cross-modal characteristic. PATIENTS AND METHODS: This prospective study enrolled healthy volunteers from local universities. After consenting, subjects underwent the Focus Analgesia Selection Task (FAST), to assess within-subjects variability of pain reports in response to experimental noxious stimuli; a taste task, which similarly assesses within-subjects variability of tastes (salty and sweet) intensity reports; and the heartbeat perception task, an interoceptive task aimed to assess how accurate subjects are in monitoring and reporting their own heartbeat. In addition, all subjects completed the Multidimensional Assessment of Interoceptive Awareness (MAIA), the Perceived Stress Scale (PSS), and Hospital Anxiety and Depression Scale (HADS). Spearman's correlations were used to assess relations between all measures. RESULTS: Sixty healthy volunteers were recruited. Variability of intensity reports of different modalities were independent of each other (P > 0.05 for all correlations). The only correlation found was within modality, between variability of intensity reports of salt and sweet tastes (Spearman's r = 0.477, P < 0.001). No correlations were found between any of the task results and questionnaire results. CONCLUSION: Within-subjects variability of pain reports do not relate to variability of reports of other modalities or to interoceptive awareness. Further research is ongoing to investigate the clinical relevance of within-subjects' variability of pain reports.

Staircase-evoked Pain May be More Sensitive Than Traditional Pain Assessments in Discriminating Analgesic Effects: A Randomized, Placebo-controlled Trial of Naproxen in Patients With Osteoarthritis of the Knee.

OBJECTIVES: Analgesic trials often fail to show a significant effect even when medications with known efficacy are tested. This could be attributed to insufficient assay sensitivity of analgesic trials, which may be due, in part, to the insensitivity of pain-related outcome measures. The aim of this methodological study was to assess the responsiveness of evoked pain generated by the staircase procedure compared with other commonly used pain outcomes in knee osteoarthritis. METHODS: This was a randomized, double-blind, placebo-controlled, cross-over trial of 1-week treatment of naproxen versus placebo. Participants were assigned to one of the 2 treatment sequences (naproxen-placebo or placebo-naproxen). Pain-at-rest, evoked pain using the Staircase-Evoked Pain Procedure (StEPP), pain diary, and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) data were collected before and at the end of each treatment sequence. RESULTS: A total of 55 osteoarthritis patients (30 M, 25 F) completed the study. Among all pain assessments, evoked pain was the most sensitive outcome to detect treatment effects, with Standardized Effect Size (SES) of 0.47 followed by the WOMAC and pain-at-rest with SES of 0.43 and 0.36, respectively. Sample size calculations demonstrated that compared with spontaneous pain, the evoked pain model reduces required number of subjects by 40%. DISCUSSION: Study results support our hypothesis that evoked pain using the StEPP may demonstrate greater responsiveness to treatment effects compared with traditional pain-related outcome measures. Accordingly, these results may facilitate development and validation of other chronic pain-related evoked pain models, which could contribute to future research and development of new analgesics.

A deeper look at pain variability and its relationship with the placebo response: results from a randomized, double-blind, placebo-controlled clinical trial of naproxen in osteoarthritis of the knee.

Previous studies have shown a robust correlation between variability of clinical pain scores and responsiveness to placebo (but not active drug) in pain studies, but explanations for these relationships are lacking. We investigated this further by assessing relationship between the Focused Analgesia Selection Test (FAST), a psychophysical method that quantifies pain reporting variability in response to experimental stimuli, variability of daily clinical pain scores as captured using diary, and response to treatment in the context of a randomized controlled crossover trial of naproxen vs placebo in knee osteoarthritis. Evoked pain using the Staircase-Evoked Pain Procedure served as the primary efficacy endpoint. Variability of daily pain scores and the FAST were assessed at baseline. Fifty-five subjects completed the study and were included in the analyses. Our results indicated a statistically significant, moderate linear relationship between variability of clinical and experimental pain reports (r = -0.416, P = 0.004). Both correlated with the placebo response (r = 0.393, P = 0.004; r =-0.371, P = 0.009; respectively), but only the FAST predicted the treatment difference between naproxen and placebo, as demonstrated both in a regression model (P = 0.002, Beta = 0.456, t = 3.342) and in a receiver operating characteristic curve (0.721) analysis. Our results extend previous findings to include a correlation between experimental pain variability and the placebo response and suggest that experimental pain variability is a better predictor of patients who respond preferentially to drug over placebo. A theoretical model unifying these observations is proposed, and practical implications are discussed.