Interactions between analgesic drug therapy and mindfulness-based interventions for chronic pain in adults: protocol for a systematic scoping review Introduction: Most current chronic pain treatment strategies have limitations in effectiveness and tolerability, and accumulating evidence points to the added benefits of rational combinations of different therapies. However, most published clinical trials of treatment combinations have involved combinations of 2 drugs, whereas very little research has been performed to characterize interactions between drug and nondrug interventions. Mindfulness-based interventions (MBIs) have been emerging as a safe and potentially effective treatment option in the management of chronic pain, but it is unclear how MBIs can and should be integrated with various other pain treatment interventions. Thus, we seek to review available clinical trials of MBIs for chronic pain to evaluate available evidence on the interactions between MBIs and various pharmacological treatments. Methods: A detailed search of trials of MBIs for the treatment of chronic pain in adults will be conducted on the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, and PsycINFO from their inception until the date the searches are run to identify relevant randomized controlled trials. Primary outcomes will include the following: (1) what concomitant analgesic drug therapies (CADTs) were allowed; (2) if and how trials controlled for CADTs and analyzed their interaction; and (3) results of available analyses of interactions between the MBI and CADT. Perspective: This review is expected to synthesize available evidence describing the interactions between MBIs and various studied drug therapies for chronic pain. Available evidence may help inform the rational integration of MBIs with drug therapy for chronic pain. Corresponding author. Address: Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital, Queen's University, Kingston, ON, K7L2V7, Canada. Tel.: 16135487827. E-mail address: gilroni@queensu.ca (I. Gilron). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Received July 01, 2019 Received in revised form September 01, 2019 Accepted September 11, 2019 This is an open access article distributed under the Creative Commons Attribution-NoDerivatives License 4.0 (CC BY-ND) which allows for redistribution, commercial and non-commercial, as long as it is passed along unchanged and in whole, with credit to the author. © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

The effect of knee resizing illusions on pain and swelling in symptomatic knee osteoarthritis: a case report Introduction: Resizing illusions that manipulate perceived body size are analgesic in some chronic pain conditions. Little is known whether such illusions may also alter other physiological features, such as swelling. Objectives: To determine the effects of a knee resizing illusion on knee pain and swelling in symptomatic osteoarthritis. Methods: This case study was extracted from a larger study evaluating the analgesic effects of resizing illusions in people with knee osteoarthritis. A mediated reality system (alters real-time video) was used to provide resizing “stretch” and “shrink” illusions of the knee. Knee pain intensity (0–100 numerical rating scale) was measured before and after illusion and after sustained (3 minutes) and repeated (n = 10) illusions. In this case study, knee swelling (leg circumference below, at, and above the knee) was also measured. Results: The 55-year-old male participant reported a long history of episodic knee pain and swelling that was subsequently diagnosed as severe osteoarthritis in 2013. In the first testing session, the participant experienced an increase in pain with the shrink illusion and a decrease in pain with stretch illusion. A noticeable increase in knee swelling was also observed. Thus, in sessions 2/3, swelling was also assessed. The stretch illusion decreased pain to the largest extent, but resulted in increased knee swelling. Repeated and sustained stretch illusions had cumulative analgesic effects but resulted in cumulative increases in swelling. While the shrink illusion increased pain, sustained (∼10 minutes) visual minification of the entire knee and leg reduced both pain and swelling. Conclusion: Our case report suggests that both pain and swelling may be modifiable by altering body-relevant sensory input in symptomatic knee osteoarthritis. Corresponding author. Address: The University of South Australia, IIMPACT in Health, GPO Box 2471, Adelaide, SA 5001, Australia. Tel.: +618 8302 2090. E-mail address: tasha.stanton@unisa.edu.au (T.R. Stanton). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Received June 04, 2019 Received in revised form October 09, 2019 Accepted October 13, 2019 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

Pain from torture: assessment and management Introduction: Survivors of torture are for many reasons at particularly high risk for inadequate assessment and management of pain. Among the many health problems associated with torture, persistent pain is frequent, particularly pain in the musculoskeletal system. The pathophysiology underlying post-torture pain is largely unknown, but pain inflicted in torture may have profound effects on neurophysiology and pain processing. Methods: A narrative review of assessment and treatment studies, informed by clinical experience, was undertaken. Results: The clinical presentation in survivors of torture shares characteristics with other chronic primary pain syndromes, including chronic widespread pain. Unfortunately, such pain is often misunderstood and dismissed as a manifestation of psychological distress, both in specialist psychosocially oriented torture services and in mainstream health care. This means that pain is at risk of not being recognized, assessed, or managed as a problem in its own right. Conclusions: The available research literature on rehabilitation for torture survivors is predominantly targeted at mental health problems, and studies of effectiveness of pain management in torture survivors are lacking. Rehabilitation is identified as a right in the UN Convention on Torture, aiming to restore as far as possible torture survivors' health and capacity for full participation in society. It is therefore important that pain and its consequences are adequately addressed in rehabilitative efforts. This article summarizes the current status on assessment and management of pain problems in the torture survivor. Corresponding author. Address: University College London, London, United Kingdom. E-mail address: amanda.williams@ucl.ac.uk (A.C.de.C. Williams). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Received June 23, 2019 Received in revised form August 26, 2019 Accepted September 17, 2019 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

Attenuation of capsaicin-induced ongoing pain and secondary hyperalgesia during exposure to an immersive virtual reality environment Introduction: There is growing evidence that virtual reality (VR) can be used in the treatment of chronic pain conditions. However, further research is required to better understand the analgesic mechanisms during sensitised pain states. Objectives: We examined the effects of an immersive polar VR environment on capsaicin-induced ongoing pain and secondary hyperalgesia. We also investigated whether the degree of analgesia was related to baseline conditioned pain modulation (CPM) responses. Methods: Nineteen subjects had baseline CPM and electrical pain perception (EPP) thresholds measured before the topical application of capsaicin cream. Visual analogue scale ratings were measured to track the development of an ongoing pain state, and EPP thresholds were used to measure secondary hyperalgesia. The effects of a passive polar VR environment on ongoing pain and secondary hyperalgesia were compared with sham VR (ie, 2D monitor screen) in responders to capsaicin (n = 15). Results: Virtual reality was associated with a transient reduction in ongoing pain and an increase in EPP thresholds in an area of secondary hyperalgesia. Baseline CPM measurements showed a significant correlation with VR-induced changes in secondary hyperalgesia, but not with VR-induced changes in ongoing pain perception. There was no correlation between VR-induced changes in pain perception and VR-induced changes in secondary hyperalgesia. Conclusion: Virtual reality can reduce the perception of capsaicin-induced ongoing pain and secondary hyperalgesia. We also show that CPM may provide a means by which to identify individuals likely to respond to VR therapy. Corresponding author. Address: The Nick Davey Laboratory, Human Performance Group, Division of Surgery, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London W6 8RF, United Kingdom. Tel.: +44 (0)20 331 38837; fax: +44 (0)20 331 38835. E-mail address: sam.hughes@imperial.ac.uk (S.W. Hughes). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Received May 09, 2019 Received in revised form July 24, 2019 Accepted September 01, 2019 This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.

Potent nonopioid antinociceptive activity of telocinobufagin in models of acute pain in mice Introduction: In recent decades, several researches have been conducted in search of new analgesics that do not present the side effects of opioids. In this context, animal venoms contain natural painkillers that have been used for the development of new analgesics. Objective: The aims of this study were to evaluate the antinociceptive effects of telocinobufagin (TCB), a bufadienolide isolated from Rhinella jimi venom, in murine acute pain models, and to verify the participation of the opioid system in these effects. Methods: TCB was purified from R. jimi venom by high-performance liquid chromatography, and its structure was confirmed by spectrometric techniques. TCB was administered intraperitoneally (i.p.) (0.062, 0.125, 0.25, 0.5, and 1 mg·kg−1) and orally (p.o.) (0.625, 1.125, 2.5, 5, and 10 mg·kg−1) in mice, which were then subjected to pain tests: acetic acid–induced writhing, formalin, tail-flick, and hot-plate. Involvement of the opioid system in TCB action was evaluated by naloxone i.p. injected (2.5 mg·kg−1) 20 minutes before TCB administration. In addition, the TCB action on the μ, δ, and κ opioid receptors was performed by radioligand binding assays. Results: In all the tests used, TCB showed dose-dependent antinociceptive activity with more than 90% inhibition of the nociceptive responses at the doses of 1 mg·kg−1 (i.p.) and 10 mg·kg−1 (p.o.). Naloxone did not alter the effect of TCB. In addition, TCB did not act on the μ, δ, and κ opioid receptors. Conclusion: The results suggest that TCB may represent a novel potential nonopioid therapeutic analgesic for treatment of acute pains. Corresponding author. Address: ISCB da Universidade Estadual do Ceará, Av. Dr. Silas Munguba, 1700-Campus do Itaperi Fortaleza, Ceará 60.714-903, Brazil. Tel.: (+55) 85-988856221; fax: (+55) 85-34866221. E-mail address: carvalhokris@gmail.com (K.M. Carvalho). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Received June 06, 2019 Received in revised form August 04, 2019 Accepted September 03, 2019 This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.