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

ABSTRACT: 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.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.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.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.

SUBMITTER: van Amerongen G

PROVIDER: S-EPMC5276025 | biostudies-other | 2016 Oct

REPOSITORIES: biostudies-other

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

van Amerongen Guido G de Boer Matthijs W MW Groeneveld Geert Jan GJ Hay Justin L JL

British journal of clinical pharmacology 20160708 4

<h4>Aims</h4>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.<h4>Methods</h4>A literature search was performed to identify randomized, double-bl ...[more]

PMID: 27203797

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Project description:BackgroundAlthough reproducibility is considered essential for any method used in scientific research, it is investigated only rarely; thus, strikingly little has been published regarding the reproducibility of evoked pain models involving human subjects. Here, we studied the reproducibility of a battery of evoked pain models for demonstrating the analgesic effects of two analgesic compounds.MethodsA total of 81 healthy subjects participated in four studies involving a battery of evoked pain tests in which mechanical, thermal and electrical stimuli were used to measure pain detection and tolerance thresholds. Pharmacodynamic outcome variables were analysed using a mixed model analysis of variance, and a coefficient of variation was calculated by dividing the standard deviation by the least squares means.ResultsA total of 76 subjects completed the studies. After being administered pregabalin, the subjects' pain tolerance thresholds in the cold pressor and pressure stimulation tests were significantly increased compared to the placebo group. Moreover, the heat pain detection threshold in UVB-irradiated skin was significantly increased in subjects who were administered ibuprofen compared to the placebo group. Variation among all evoked pain tests ranged from 2.2% to 30.6%.ConclusionsFour studies using a similar design showed reproducibility with respect to the included evoked pain models. The relatively high consistency and reproducibility of two analgesics at doses known to be effective in treating clinically relevant pain supports the validity of using this pain test battery to investigate the analgesic activity and determine the active dosage of putative analgesic compounds in early clinical development.SignificanceThe consistency and reproducibility of measuring the profile of an analgesic at clinically relevant doses illustrates that this pain test battery is a valid tool for demonstrating the analgesic activity of a test compound and for determining the optimal active dose in early clinical drug development.

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

Publications

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

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