Beyond labeled lines: A population coding account of the thermal grill illusion

Heat and pain illusions (synthetic heat and the thermal grill illusion) can be generated by simultaneous cold and warm stimulation on the skin at temperatures that would normally be perceived as innocuous in isolation. Historically, two key questions have dominated the literature: which specific pathway conveys the illusory perceptions of heat and pain, and where, specifically, does the illusory pain originate in the central nervous system? Two major theories - the addition and disinhibition theories - have suggested distinct pathways, as well as specific spinal or supraspinal mechanisms. However, both theories fail to fully explain experimental findings on illusory heat and pain phenomena. We suggest that the disagreement between previous theories and experimental evidence can be solved by abandoning the assumption of one-to-one relations between pathways and perceived qualities. We argue that a population coding framework, based on distributed activity across non-nociceptive and nociceptive pathways, offers a more powerful explanation of illusory heat and pain. This framework offers new hypotheses regarding the neural mechanisms underlying temperature and pain perception

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.

Efficacy of Patient Education and Duloxetine, Alone and in Combination, for Patients With Multisystem Functional Somatic Disorder: Study Protocol for the EDULOX Trial

Background Multisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment. Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with not antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. Methods This is a nested study design. The parent trial EDULOX1 (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded randomized controlled trial, EDULOX2 (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. Conclusion The EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education