A systematic review of experimental methods to manipulate secondary hyperalgesia in humans: protocol

Abstract

Background Neuropathic pain affects 7–10% of people, but responds poorly to pharmacotherapy, indicating a need for better treatments. Mechanistic research on neuropathic pain frequently uses human surrogate models of the secondary hyperalgesia that is a common feature of neuropathic pain. Experimentally induced secondary hyperalgesia has been manipulated with pharmacological and non-pharmacological methods to clarify the relative contributions of different mechanisms to secondary hyperalgesia. However, this literature has not been systematically synthesised. The aim of this systematic review is to identify, describe, and compare methods that have been used to manipulate experimentally induced secondary hyperalgesia in healthy humans. Methods A systematic search strategy will be supplemented by reference list checks and direct contact with identified laboratories to maximise the identification of data reporting the experimental manipulation of experimentally induced secondary hyperalgesia in healthy humans. Duplicated screening, risk of bias assessment, and data extraction procedures will be used. Authors will be asked to provide data as necessary. Data will be pooled and meta-analyses conducted where possible, with subgrouping according to manipulation method. Manipulation methods will be ranked for potency and risk. Discussion The results of this review will provide a useful reference for researchers interested in using experimental methods to manipulate secondary hyperalgesia in humans and will help to clarify the relative contributions of different mechanisms to secondary hyperalgesia. Systematic review registration This protocol will be registered on PROSPERO before the review begins. Review records will be updated on PROSPERO once the review is complete. This review is intended for publication in a peer-reviewed journal. Analyses and scripts will be made publicly available. Electronic supplementary material The online version of this article (10.1186/s13643-019-1120-7) contains supplementary material, which is available to authorized users.

Challenges and opportunities in translational pain research – An opinion paper of the working group on translational pain research of the European pain federation (EFIC)

“…Observations made in healthy volunteers – including several observations that tend to replicate observations made in animal models of pain such as the induction of secondary hyperalgesia by high‐frequency electrical stimulation of nociceptive afferents, cold injury, an experimental incision or capsaicin (Fißmer et al., 2011 ; Klein et al., 2005 ; Madden et al., 2019 ), and the inhibitory effects of CPM have contributed to a better understanding of the mechanisms underlying pain perception and its modulation. A driving motivation for this research is that it could also lead to a better understanding of the mechanisms underlying the pain experienced by patients and, thereby, to new diagnostic and therapeutic approaches.…”