Abstract
BackgroundNeuropathic 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.MethodsA 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.DiscussionThe 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 registrationThis 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.
Highlights
Rationale Neuropathic pain (NP) currently affects 6.9–10% of the general population [1] and has severe consequences for the individual and for society
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
Summary
Rationale Neuropathic pain (NP) currently affects 6.9–10% of the general population [1] and has severe consequences for the individual and for society. A single model cannot account for all the possible features of clinical NP, experimentally induced secondary hyperalgesia has been widely used as a laboratory-based human surrogate model in studies that aim to elucidate the mechanisms that underlie neuropathic pain [7,8,9,10,11]. While secondary hyperalgesia is typically considered the primary outcome of studies that use these inductions, secondary outcomes may include primary hyperalgesia, secondary allodynia, and the surface area of secondary hyperalgesia These outcomes can be compared to identify the relative contributions of different mechanisms. Induced secondary hyperalgesia has been manipulated with pharmacological and non-pharmacological methods to clarify the relative contributions of different mechanisms to secondary hyperalgesia. 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
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