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.