Virtual reality increases pressure pain threshold and lowers anxiety in children compared with control and non-immersive control-A randomized, crossover trial.

BACKGROUND: Virtual reality (VR) is a promising non-pharmacological pain intervention because it may not only distract but also modulate pain by immersing the user in a three-dimensional 360° alternate reality. In children, VR has been reported to reduce clinical pain and anxiety during medical procedures. However, the effect of immersive VR on pain and anxiety remains to be investigated in randomized controlled trials (RCT). The aim of the present crossover RCT was to assess the effect of VR on pressure pain threshold (PPT) and anxiety level measured with the modified Yale Preoperative Anxiety Scale (mYPAS) in children in a controlled experimental setting. METHODS: Seventy-two children (mean age 10.2 (6-14) years) were randomized to 24 sequences of four interventions (immersive VR Game, immersive VR video, tablet: 2D video and control: small talk). Outcome measures PPT, mYPAS and heart rate were assessed before and after each intervention. RESULTS: PPT increased significantly during VR game (PPTdiff): 136 kPa (CI 112; 161), p < 0.0001 and VR Video (PPTdiff): 122 kPa (CI 91; 153), p < 0.0001. Also, anxiety levels significantly decreased during both VR game (mYPASdiff: -7 points (-8 to -5), p < 0.0001) and VR video (mYPASdiff: -6 points (CI -7; -4), p < 0.0001). CONCLUSIONS: VR had a marked beneficial effect on PPT and anxiety compared with the control interventions: 2D video and small talk. Thus, immersive VR had a distinct modulatory effect on pain and anxiety in a well-controlled experimental setting. Immersive VR was effective and feasible in children and can act as a valid tool for non-pharmacological pain and anxiety management. SIGNIFICANCE: Paediatric immersive VR seems to be beneficial although well-controlled studies are pending. We investigated whether immersive VR can modulate children's threshold for pain and anxiety level in an experimental well-controlled setting. We document a modulatory pain threshold increase and anxiety level decrease compared with extensive control conditions. Paediatric immersive VR is effective, feasible and valid for non-pharmacological pain and anxiety management. All efforts to reach the goal that no child should experience pain or anxiety when exposed to medical procedures.

Psychological interventions improve quality of life despite persistent pain in endometriosis: results of a 3-armed randomized controlled trial.

PURPOSE: Despite standard medical treatment endometriosis is often associated with disabling pain and poor quality of life (QoL). Studies indicate that psychological interventions (PIs) may improve pain and QoL, yet studies on the effects of PIs for women with endometriosis are sparse and limited by low-quality study designs. Therefore, this study aimed, in a rigorous three-armed design, to evaluate the effect of PIs on chronic pelvic pain (CPP) and QoL in women with endometriosis. METHODS: This three-armed parallel, multi-center randomized controlled trial included fifty-eight endometriosis patients reporting severe CPP [≥ 5 for pain intensity measured on a 0-10-point numeric rating scale (NRS)]. Patients were randomly assigned to (1) Specific mindfulness- and acceptance-based psychological intervention (MY-ENDO), (2) Carefully matched non-specific psychological intervention (Non-specific), or (3) A wait-list control group (WL). The primary outcome was pelvic pain intensity/unpleasantness measured on NRS. Secondary outcomes included endometriosis-related quality of life, workability, pain acceptance, and endometriosis-related symptoms. Differences in outcomes between groups at post-treatment follow-up were analyzed using mixed linear models. Analyses were performed on an intention-to-treat basis. RESULTS: Compared to WL, psychological intervention (MY-ENDO + Non-specific) did not significantly reduce pain. However, psychological intervention did significantly improve the QoL-subscales 'control and powerlessness', 'emotional well-being', and 'social support' as well as the endometriosis-related symptoms 'dyschezia' and 'constipation'. MY-ENDO was not superior to Non-specific. CONCLUSIONS: Women with endometriosis may have significant and large effects of psychological intervention on QoL despite an ongoing experience of severe CPP. TRIAL REGISTRATION: 12 April 2016, clinicaltrials.gov (NCT02761382), retrospectively registered.

La realidad virtual eleva el umbral de dolor por presión y reduce la ansiedad en niños comparada con controles y controles no inmersivos. Un estudio aleatorizado y cruzado / Virtual reality increases pressure pain threshold and lowers anxiety in children compared with control and non-immersive control-randomized, crossover trial

Antecedentes: La realidad virtual (RV) es una intervención del dolor no farmacológica y prometedora porque es capaz no solo de distraer el dolor sino también de modularlo sumergiendo al usuario en una realidad paralela tridimensional de 360°. Se ha informado que, en niños, la RV reduce el dolor clínico y la ansiedad durante las intervenciones médicas. No obstante, se siguen investigando los efectos de la RV inmersiva sobre el dolor y la ansiedad mediante ensayos controlados aleatorios (ECA). El objetivo del presente ECA cruzado es la evaluación de los efectos de la RV sobre el umbral dedolor por presión (UDP) y el nivel de ansiedad medidos con la modified Yale Preoperative Anxiety Scale (mYPAS) en niños en un entorno experimental controlado. Metodología: Un total de setenta y dos niños (edad promedio de 10,2 (6 a 14) años) fueron asignados aleatoriamente a 24 secuencias de cuatro intervenciones (juego de RV inmersiva, vídeo de RV inmersiva, tableta electrónica: vídeo en 2D y controles: pequeña charla). Antes y después de cada intervención se evaluaron las medidas de resultados siguientes: UDP, mYPAS y frecuencia cardiaca.Resultados: Se observó un aumento significativo en el UDP durante el juego de RV (PPTdiff): 136kPa (CI 112; 161), p < 0,0001 y vídeo de RV (PPTdiff): 122kPa (CI 91; 153), p < 0,0001. Además, los niveles de ansiedad disminuyeron de forma significativa durante el juego de RV (mYPASdiff: −7 puntos (−8 a −5), p < 0,0001) y el vídeo de RV (mYPASdiff: −6 puntos (CI −7; −4), p < 0,0001). Conclusiones: La RV demostró tener unos efectos notablemente beneficiosos sobre el UDP y la ansiedad comparada con las intervenciones de control: vídeo en 2D y pequeña charla. Así, la RV inmersiva tuvo un efecto modulatorio distintivo sobre el dolor y la ansiedad en un entorno experimental adecuadamente controlado.(AU)

Background: Virtual reality (VR) is a promising non-pharmacological pain intervention because it may not only distract but also modulate pain by immersing the user in a three-dimensional 360° alternate reality. In children, VR has been reported to reduce clinical pain and anxiety during medical procedures. However, the effect of immersive VR on pain and anxiety remains to be investigated in randomized controlled trials (RCT). The aim of the present crossover RCT was to assess the effect of VR on pressure pain threshold (PPT) and anxiety level measured with the modified Yale Preoper-ative Anxiety Scale (mYPAS) in children in a controlled experimental setting. Methods: Seventy-two children (mean age 10.2 (6–14) years) were randomized to 24 sequences of four interventions (immersive VR Game, immersive VR video, tablet: 2D video and control: small talk). Outcome measures PPT, mYPAS and heart rate were assessed before and after each intervention. Results: PPT increased significantly during VR game (PPTdiff): 136 kPa (CI 112; 161), p < 0.0001 and VR Video (PPTdiff): 122 kPa (CI 91; 153), p < 0.0001. Also, anxiety levels significantly decreased during both VR game (mYPASdiff: −7 points (−8 to −5), p < 0.0001) and VR video (mYPASdiff: −6 points (CI −7; −4), p < 0.0001).Conclusions: VR had a marked beneficial effect on PPT and anxiety compared with the control interventions: 2D video and small talk. Thus, immersive VR had a distinct modulatory effect on pain and anxiety in a well-controlled experimental setting. Immersive VR was effective and feasible in children and can act as a valid tool for non-pharmacological pain and anxiety management...(AU)

How May Placebo Mechanisms Influence Orofacial Neuropathic Pain?

The conceptualization of placebo has changed from inactive pills to a detailed understanding of how patients' perception of receiving a treatment influences pain processing and overall treatment outcome. Large placebo effects were recently demonstrated in chronic neuropathic pain, thereby opening the question of whether placebo effects also apply to orofacial neuropathic pain. In this article, we review the new definitions, magnitude, and social, psychological, neurobiologic, and genetic mechanisms of placebo effects in pain, especially neuropathic pain, to illustrate that placebo effects are not simply response bias but psychoneurobiological phenomena that can be measured at many levels of the neuroaxis. We use this knowledge to carefully illustrate how patients' perceptions of the treatment, the relationship with the health care provider, and the expectations and emotions toward a treatment can influence test and treatment outcome and potentially skew the results if they are not taken into consideration. Orofacial neuropathic pain is a new research area, and we review the status on definition, diagnosis, mechanisms, and pharmacologic treatment of neuropathic pain after trigeminal nerve injury, as this condition may be especially influenced by placebo factors. Finally, we have a detailed discussion of how knowledge of placebo mechanisms may help improve the understanding, diagnosis, and treatment of orofacial neuropathic pain, and we illustrate pitfalls and opportunities of applying this knowledge to the test of dental treatments.

A novel neurocognitive approach for placebo analgesia in neurocognitive disorders.

Neural correlates of placebo analgesia (PA) in patients with neurocognitive disorders have not yet been elucidated. The present study aimed to evaluate how and to what extent executive (dys)functions of the medial prefrontal cortex (MPFC) may be related to PA. To this end, twenty-three subjects complaining of different cognitive deficits (from mild cognitive impairment likely due to Alzheimer's disease to mild AD) were recruited. PA was investigated by a well-known experimental venipuncture pain paradigm (open versus hidden [O-H] application of lidocaine). Patients also underwent a comprehensive neuropsychological evaluation and a functional magnetic resonance imaging (fMRI) GO/No-GO task for eliciting selective activation of the MPFC. Selected neuropsychological variables were correlated to the OH-PA paradigm. The association between the fMRI response on the "No-GO" versus "GO" contrast and PA was investigated over the whole-brain by regression analysis. We showed the existence of a relationship between a lower PA and MPFC dysfunctions through the neuropsychological and fMRI assessment. A separate voxel-based morphometry (VBM) analysis controlled for possible influence of grey matter (GM) volume reduction on both fMRI results and PA. fMRI results were not directly affected by, and therefore independent of, disease-specific GM atrophy, which was indeed located more anteriorly within the rostral anterior cingulate and inversely correlated with PA. Our findings shed new light on the underestimated contribution of executive (dys)functions mediated by the MPFC (response-inhibition, self-monitoring and set-shifting abilities) in PA pathogenesis, with a special purely (i.e. independently from brain structural alterations) functional role played by the MCC. Results are discussed in terms of possible clinical relevance in the management of patients with neurocognitive disorders.

Does conditioned pain modulation predict the magnitude of placebo effects in patients with neuropathic pain?

BACKGROUND: Conditioned pain modulation (CPM) is a validated measure of the function of endogenous pain inhibitory pathways. Placebo effects reflect top-down inhibitory modulation of pain. CPM and placebo effects are both influenced by expectations, albeit to varying degrees, and are related to neurotransmitter systems such as the endogenous opioid system, and it can be speculated that CPM responses are positively associated with the magnitude of placebo effects. Yet, no studies have tested this. METHODS: The study included 19 patients with neuropathic pain. CPM was quantified as the difference in pressure pain threshold (PPT) as measured at the middle deltoid muscle before and after 5-min exposure to the cold pressor test (CPT) (conditioning pain stimulus). Placebo effects were tested via open and hidden applications of the pain-relieving agent lidocaine (2 mL) using a disinfection napkin controlled for no treatment. RESULTS: The mean (SD) PPT was 668.7 (295.7) kPa before and 742.3 (370.8) kPa after the CPT. The mean (SD) CPM response was -73.6 (214.0) kPa corresponding to an 11% increase in PPT, reflecting a normally functioning endogenous pain modulatory system. Large and significant placebo effects were observed in ongoing neuropathic pain intensity (p = 0.002). The CPM response did not predict the magnitude of the placebo effect (p = 0.765). Moreover, there were no interaction effects for the moderator variables: clinical pain level (p = 0.136), age (p = 0.347) and gender (p = 0.691). CONCLUSIONS: Conditioned pain modulation and placebo effects do not seem to be associated in patients with neuropathic pain. SIGNIFICANCE: Conditioned pain modulation and placebo effects are endogenous pain-modulating phenomena that are influenced by some of the same mechanisms. This study suggests that CPM and placebo effects in neuropathic pain are independent phenomena that may be mediated by different mechanisms.

Multisensory modulation of experimentally evoked perceptual distortion of the face.

BACKGROUND: Chronic oro-facial pain patients often perceive the painful face area as "swollen" without clinical signs, that is a perceptual distortion (PD). Local anaesthetic (LA) injections in healthy participants are also associated with PD. OBJECTIVE: The aim was to explore whether PD evoked by LA into the infraorbital region could be modulated by adding mechanical stimulation (MS) to the affected area. METHODS: Mechanical stimulation was given with a brush and a 128-mN von Frey filament. Firstly, sixty healthy participants were randomly divided into three groups: (i) LA control, (ii) LA with MS, (iii) isotonic solution (ISO) with MS as an additional control condition. To further examine the role of a multisensory modulation, an additional experiment was conducted. Twenty participants received LA with MS (filament) in addition to visual feedback of their distorted face. The results of the two experiments are presented together. RESULTS: All three LA groups experienced PD; per contra, PD was not reported in the ISO group. MS alone did not change the magnitude of PD: brush (P = .089), filament (P = .203). However, when the filament stimulation was combined with additional visual information of a distorted face, there was observable decrease in PD (P = .002). CONCLUSION: The findings indicate the importance of multisensory integration for PD and represent a significant step forward in the understanding of the factors that may influence this common condition. Future studies are encouraged to investigate further the cortical processing for possible implications for PD in pain management.

Reports of perceptual distortion of the face are common in patients with different types of chronic oro-facial pain.

Anecdotally, chronic oro-facial pain patients may perceive the painful face area as 'swollen'. Because there are no clinical signs, these self-reported 'illusions' may represent perceptual distortions and can be speculated to contribute to the maintenance of oro-facial pain. This descriptive study investigated whether chronic oro-facial pain patients experience perceptual distortions - a kind of body image disruption. Sixty patients were consecutively recruited to fill in questionnaires regarding i) pain experience, ii) self-reports of perceptual distortion and iii) psychological condition. Perceptual distortions were examined in the total group and in three diagnostic subgroups: i) painful post-traumatic trigeminal neuropathy (PPTN), ii) painful temporomandibular disorder (TMD) or iii) persistent idiopathic facial pain (PIFP). A large proportion of oro-facial pain patients reported perceptual distortions of the face (55·0%). In the diagnostic subgroups, perceptual distortions were most pronounced in PPTN patients (81·5%) but with no significant group differences. In the total group of chronic oro-facial pain patients, the present pain intensity explained 16·9% of the variance in magnitude of the perceptual distortions (R(2) = 16·9, F(31) = 6·3, P = 0·017). This study demonstrates that many chronic oro-facial pain patients may experience perceptual distortions. Future studies may clarify the mechanisms underlying perceptual distortions, which may point towards new complementary strategies for the management of chronic oro-facial pain.

Nocebo vs. placebo: the challenges of trial design in analgesia research.

The placebo effect in randomized clinical trials appears to have increased thereby contributing to problems of demonstrating statistically reliable effects of treatments that directly target biological mechanisms. The shortcomings of randomized clinical trials are currently discussed along with potential improvements of trial designs. In this review we explain how utilizing knowledge from the placebo and nocebo mechanisms literature could improve the information that can be obtained from randomized clinical trials. We present three major challenges in randomized clinical trials: (i) increasing placebo effects, (ii) variability of the placebo effect, and (iii) risk of un-blinding. We then explain how recent placebo and nocebo studies of effects of verbal suggestion, expectancy, and emotions may improve understanding and discussion of increasing placebo effects, account/control for large parts of the variability of placebo effects, and suggest ways to improve blinding in future trials.

Pre-operative baroreflex sensitivity and efferent cardiac parasympathetic activity are correlated with post-operative pain.

BACKGROUND: A maladaptation of the autonomic nervous system may been seen in patients with chronic pain that includes persistent changes in the autonomic tone, increased heart rate, and reduced heart rate variability and baroreflex sensitivity. Baroreflex sensitivity and acute pain intensity have been reported to be inversely correlated. However, it is unknown whether the same correlation applies with regard to post-operative pain. In the present study, autonomic function was measured in patients scheduled for minor hand surgery and correlated with early and persistent pain after the procedure. Thus, the cause (autonomic imbalance) was present before the effect (post-operative pain). Our primary hypothesis was that a lower level of pre-operative baroreflex sensitivity is correlated with increased early post-operative pain. METHODS: There were 30 patients included and scheduled for open carpal tunnel surgery. Baroreflex sensitivity and heart rate variability were measured before surgery. Efferent cardiac parasympathetic activity was estimated by power spectral analysis of heart rate variability. Post-operative pain was recorded daily for 6 weeks (early post-operative pain) and for 1 week 1 year after surgery (persistent post-operative pain). RESULTS: Pre-operative baroreflex sensitivity correlated negatively with early (P=0.05) and persistent (P=0.04) post-operative pain. Efferent cardiac parasympathetic activity correlated negatively with early (P=0.03) but not persistent post-operative pain (P=0.12). CONCLUSIONS: The findings suggest that a low pre-operative level of baroreflex sensitivity is associated with higher post-operative pain intensity. To our knowledge, this is the first study to show the correlation between baroreflex sensitivity and post-operative pain.