Comprehensive review The magnitude of nocebo effects in pain: A meta-analysis

a b s t r a c t The investigation of nocebo effects is evolving, and a few literature reviews have emerged, although so far without quantifying such effects. This meta-analysis investigated nocebo effects in pain. We searched the databases PubMed, EMBASE, Scopus, and the Cochrane Controlled Trial Register with the term ''nocebo.'' Only studies that investigated nocebo effects as the effects that followed the administration of an inert treatment along with verbal suggestions of symptom worsening and that included a no-treatment control condition were eligible. Ten studies fulfilled the selection criteria. The effect sizes were calculated using Cohen's d and Hedges' g. The overall magnitude of the nocebo effect was moderate to large (lowest g = 0.62 [0.24-1.01] and highest g = 1.03 [0.63-1.43]) and highly variable (range of g = À0.43 to 4.05). The magnitudes and range of effect sizes was similar to those of placebo effects (d = 0.81) in mechanistic studies. In studies in which nocebo effects were induced by a combination of verbal suggestions and conditioning, the effect size was larger (lowest g = 0.76 [0.39-1.14] and highest g = 1.17 [0.52-1.81]) than in studies in which nocebo effects were induced by verbal suggestions alone (lowest g = 0.64 [À0.25 to 1.53] and highest g = 0.87 [0.40-1.34]). These findings are similar to those in the placebo literature. As the magnitude of the nocebo effect is variable and sometimes large, this meta-analysis demonstrates the importance of minimizing nocebo effects in clinical practice.

Axonal excitability does not differ between painful and painless diabetic or chemotherapy-induced distal symmetrical polyneuropathy in a multi-centre observational study

OBJECTIVE: Axonal excitability reflects ion channel function and it is proposed that this may be a biomarker in painful (versus painless) polyneuropathy. Our objective was to investigate the relationship between axonal excitability parameters and chronic neuropathic pain in deeply phenotyped cohorts with diabetic or chemotherapy induced distal symmetrical polyneuropathy. METHODS: 239 participants with diabetic polyneuropathy were recruited from sites in the UK and Denmark, and 39 participants that developed chemotherapy-induced polyneuropathy were recruited from Denmark. Participants were separated into those with probable or definite neuropathic pain and those without neuropathic pain. Axonal excitability of large myelinated fibres was measured with the threshold tracking technique. The stimulus site was the median nerve and the recording sites were the index finger (sensory studies) and abductor pollicis brevis muscle (motor studies). RESULTS: Participants with painless and painful polyneuropathy were well matched across clinical variables. Sensory and motor axonal excitability measures, including recovery cycle, threshold electrotonus, strength duration time constant, and current-threshold relationship, did not show differences between participants with painful and painless diabetic polyneuropathy, while there were only minor changes for chemotherapy-induced polyneuropathy. INTERPRETATION: Axonal excitability did not significantly differ between painful and painless diabetic or chemotherapy induced polyneuropathy in a multi-centre observational study. Threshold tracking assesses the excitability of myelinated axons; the majority of nociceptors are unmyelinated and although there is some overlap of the 'channelome' between these axonal populations, our results suggest that alternative measures such as microneurography are required to understand the relationship between sensory neuron excitability and neuropathic pain. This article is protected by copyright. All rights reserved

Pain frequency moderates the relationship between pain catastrophizing and pain

Background Pain frequency has been shown to influence sensitization, psychological distress and pain modulation. The present study examined if pain frequency moderates the relationship between pain catastrophizing and pain. Method A non-clinical (247 students) and a clinical (223 pain patients) sample completed the Danish versions of the Pain Catastrophizing Scale, Beck Depression Inventory and the State Trait Anxiety Inventory and rated pain intensity, unpleasantness and frequency Results In both samples, high pain frequency was found to moderate the association between pain catastrophizing and pain intensity, whereas low pain frequency did not. The psychometric properties and the factor structure of the Danish version of the PCS were confirmed.Conclusions This is the first study to validate the Danish version of the PCS and to show that pain frequency moderates the relationship between pain catastrophizing and reported pain in both non-clinical and clinical populations