, T. (2019). Assessment of conditioned pain modulation in healthy participants and patients with chronic pain: manifestations and implications for pain progression.

Background Efficacy of pain modulation is assessed as the difference in pain sensitivity during a painful conditioning, compared to before (conditioning pain modulation, CPM). Attention can be assessed with the Stroop task, in which participants report the number of words on a screen; either congruent or incongruent with the value of the words. Attention away from painful stimuli during CPM enhances the CPM effect. However, it is unknown if attention influences CPM effects when the two are done in sequence. Methods Healthy men (n = 25) underwent cuff algometry CPM‐assessment where the pressure‐pain detection and tolerance thresholds (PTT) were recorded on one leg with and without contralateral conditioning. Two identical sessions of four test stimuli equal to PTT (5 s, 1‐min interval, scored on a visual analogue scale, VAS) with a painful conditioning from the second to the last test‐stimulus were performed. Stroop sessions were followed by test stimuli with or without painful conditioning. Results The VAS scores in the first two sessions showed excellent reliability (ICC = 0.92). VAS scores were lower in sessions with Stroop compared to sessions without Stroop (p = .05) indicating an analgesic effect of Stroop. Participants were subgrouped into CPM responders and CPM non‐responders according to CPM effects in the first two sessions. CPM non‐responders (n = 13) showed facilitation to repeated noxious stimuli in all sessions with no effect of conditioning or Stroop (p = .02). Conclusion Attention and CPM both modulate pain in healthy men. Attention‐induced analgesia works in CPM non‐responders. Results indicate that attention and CPM are not the same and that they do not demonstrate additive effects when applied in sequence. Significance Pain sensitivity is reduced after an attention task in healthy men. The delayed effects from attention only have minor effects on Conditioned Pain Modulation (CPM), and results support that attention‐driven analgesia works independently of CPM. Results indicate that individual strategies for pain inhibition exist and that an overlap between the mechanisms of CPM and selective attention is limited. Moreover, painful phasic stimuli may increase the number of healthy volunteers with negative CPM effects.

IMPORTANCE Persistent (>4 weeks) postconcussion symptoms (PPCS) are challenging for both patients and clinicians. There is uncertainty about the effect of commonly applied nonpharmacological treatments for the management of PPCS. OBJECTIVE To systematically assess and summarize evidence for outcomes related to 7 nonpharmacological interventions for PPCS in adults (aged >18 years) and provide recommendations for clinical practice. DATA SOURCES Systematic literature searches were performed via Embase, MEDLINE, PsycINFO, CINAHL, PEDro, OTseeker, and Cochrane Reviews (via MEDLINE and Embase) from earliest possible publication year to March 3, 2020. The literature was searched for prior systematic reviews and primary studies. To be included, studies had to be intervention studies with a control group and focus on PPCS. STUDY SELECTION A multidisciplinary guideline panel selected interventions based on frequency of use and need for decision support among clinicians, including early information and advice, graded physical exercise, vestibular rehabilitation, manual treatment of neck and back, oculomotor vision treatment, psychological treatment, and interdisciplinary coordinated rehabilitative treatment. To be included, studies had to be intervention studies within the areas of the predefined clinical questions, include a control group, and focus on symptoms after concussion or mild traumatic brain injury. DATA EXTRACTION AND SYNTHESIS Extraction was performed independently by multiple observers. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data abstraction and data quality assessment. Included studies were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) tool and the Cochrane Risk of Bias (randomized clinical trials) tool. Meta-analysis was performed for all interventions where possible. Random-effects models were used to calculate pooled estimates of effects. The level and certainty of evidence was rated and recommendations formulated according to the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework. MAIN OUTCOMES AND MEASURESAll outcomes were planned before data collection began according to a specified protocol. The primary outcomes were the collective burden of PPCS and another outcome reflecting the focus of a particular intervention (eg, physical functioning after graded exercise intervention). RESULTSEleven systematic reviews were identified but did not contribute any primary studies; 19 randomized clinical trials comprising 2007 participants (1064 women [53.0%]) were separately (continued)

Conditioning pain modulation can be assessed in 5-min intervals by cuff algometry with a fixed conditioning stimulus. Without applying conditioning stimuli the pain sensitivity of test-stimuli habituated. As a consequence, it can be speculated that the conditioning stimulus may negate the temporal habituation effects during repeated sessions, whereas this may not be the case for unconditioned stimuli. Applying both conditioned and unconditioned repeated test-stimuli may be a way to assess different parts of the pain modulatory system, and a model for measuring a netCPM-effect, which could indicate a balance between habituation and sensitization, is proposed.