Opioid-based analgesics provide the mainstay for attenuating burn pain, but they have a
myriad of side effects including respiratory depression, nausea, impaired gastrointestinal
motility, sedation, dependence, physiologic tolerance, and opioid-induced hyperalgesia. To
test and develop novel analgesics, validated burn-relevant animal models of pain are
indispensable. Herein we review such animal models, which are mostly limited to rodent
models of burn-induced, inflammatory, and neuropathic pain. The latter two are pain
syndromes that provide insight into the pain caused by systemic pro-inflammatory cytokines
and direct injury to nerves (e.g., after severe burn), respectively. To date, no single
animal model optimally mimics the complex pathophysiology and pain that a human burn
patient experiences. No currently available burn-pain model examines effects of pharmacological
intervention on wound healing. As cornerstones of pain and wound healing, proinflammatory
mediators may be utilized for insight into both processes. Moreover, common
clinical concerns such as systemic inflammatory response syndrome and multiple organ
dysfunction remain unaddressed. For development of analgesics, these aberrations can
significantly alter the potential efficacy and/or adverse effects of a prescribed analgesic
following burn trauma. We therefore suggest that a multi-model strategy would be the most
clinically relevant when evaluating novel analgesics for use in burn patients.