Methodology and applicability of the human contact burn injury model: A systematic review

Abstract

The contact burn injury model is an experimental contact thermode-based physiological pain model primarily applied in research of drug efficacy in humans. The employment of the contact burn injury model across studies has been inconsistent regarding essential methodological variables, challenging the validity of the model. This systematic review analyzes methodologies, outcomes, and research applications of the contact burn injury model. Based on these results, we propose an improved contact burn injury testing paradigm. A literature search was conducted (15-JUL-2020) using PubMed, EMBASE, Web of Science, and Google Scholar. Sixty-four studies were included. The contact burn injury model induced consistent levels of primary and secondary hyperalgesia. However, the analyses revealed variations in the methodology of the contact burn injury heating paradigm and the post-burn application of test stimuli. The contact burn injury model had limited testing sensitivity in demonstrating analgesic efficacy. There was a weak correlation between experimental and clinical pain intensity variables. The data analysis was limited by the methodological heterogenicity of the different studies and a high risk of bias across the studies. In conclusion, although the contact burn injury model provides robust hyperalgesia, it has limited efficacy in testing analgesic drug response. Recommendations for future use of the model are being provided, but further research is needed to improve the sensitivity of the contact burn injury method. The protocol for this review has been published in PROSPERO (ID: CRD42019133734).

Fig 1. PRISMA flow diagram for the search algorithm [68].

Fig 2. Time-temperature relationship of the contact burn injury.

Double-logarithmic time-temperature relationship of the burn injury (left panel) and inclusion criteria for minimum exposure temperature and exposure time (right panel). The grey line represents a regression plot with 95% confidence bands (dashed red lines) on the logarithmic relationship between exposure temperature (X) and exposure time (Y) in producing a burn injury (modified from Naert et al. [27] based on data from Moritz and Henriques [72]; Y = -28.3*X + 116.4, R² = 0.98). The open circles represent the longest exposure time at a given temperature that failed to destroy the epidermis but induced a hyperemic skin response in humans. The red line is a parallel shift of the regression line through the heating paradigm of 300 s at 45°C (Y = -28.3*X + 113.4), serving as a ‘safety margin’ and inclusion criteria in this review (see right panel for specific values). The solid grey circles represent the heating paradigms of the included studies. The minimum exposure time at a given temperature that meets the inclusion criteria is outlined in the table (right panel, corresponding to the parallel shifted red line).