A literature review on the pharmacological sensitivity of human evoked hyperalgesia pain models

Aims: Human evoked pain models can be used to determine the efficacy of new and existing analgesics and to aid in the identification of new targets. Aspects of neuropathic pain can be simulated by inducing hyperalgesia resulting from provoked sensitization. The present literature review aimed to provide insight into the sensitivity of different hyperalgesia and allodynia models of pharmacological treatment.

Methods: A literature search was performed to identify randomized, double-blind, placebo-controlled studies that included human hyperalgesia pain models and investigated the pharmacodynamic effects of different classes of drugs.

Results: Three hyperalgesia models [ultraviolet B (UVB) irradiation, capsaicin and thermode burn] have been used extensively. Assessment of hyperalgesia/allodynia and pharmacological effect are measured using challenge tests, which generally comprise thermal (heat/cold) or mechanical stimulation (pin-prick, stroking or impact). The UVB model was sensitive to the antihyperalgesic effects of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids. The capsaicin model was partially sensitive to opioids. The burn model did not detect any antihyperalgesic effects when NSAIDs or local anaesthetics were administered but responded to the effects of N-methyl D-aspartate (NMDA) receptor antagonists by moderately reducing mechanical hyperalgesia.

Conclusions: Based on pharmacological sensitivity, the UVB model adequately reflects inflammatory pain and was sensitive to NSAIDs and opioids. Findings from the capsaicin and burn models raised questions about the translatability of these models to the treatment of neuropathic pain. There is a need for a reproducible and predictive model of neuropathic pain, either in healthy subjects or in patients.