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Latest publication 04/30/2006

Hyperalgesia induced by cutaneous freeze injury for testing analgesics in health

Aims: The early phases of the clinical development of new analgesic agents are severely hindered by a lack of reliable sensitive tests based on...

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    [title] => Hyperalgesia induced by cutaneous freeze injury for testing analgesics in health
    [paragraph] => Hyperalgesia induced by cutaneous freeze injury for testing analgesics in healthy volunteers.
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Authors
C. Chassaing, J. Schmidt, A. Eschalier, J. M. Cardot, C. Dubray.

 Lab
INSERM, CIC 501 and U 766, Clermont-Ferrand, France ; University Clermont 1, Fac Médecine, Pharmacologie Médicale, Clermont-Ferrand, France ; CHU Clermont-Ferrand, Hôpital Gabriel Montpied, Services Urgences and Pharmacologie, Clermont-Ferrand, France.
Journal
British Journal of Clinical Pharmacology
Abstract
Aims: The early phases of the clinical development of new analgesic agents are severely hindered by a lack of reliable sensitive tests based on experimental pain models. The aim of this study was to assess the ability of a localized hyperalgesia model induced by cutaneous freeze injury to evaluate the pharmacodynamic profile of weak analgesic agents in healthy volunteers. Method and results: Two groups of 24 healthy volunteers were enrolled in controlled, randomized, double-blind, cross-over studies. After freeze injury, punctate mechanical pain thresholds (MPT) were measured over three consecutive daily sessions to characterize the induced hyperalgesia and compare the effects of (i) oral ibuprofen and acetaminophen and (ii) oral and topical ibuprofen vs. placebo. The freeze injury model provides two types of hyperalgesia, primary and secondary, stable over 72 h. The MPT values (means; 95% confidence interval) in the primary (38.9 g; 34.3, 43.5) and secondary (82.2 g; 81.4, 88.0) areas of hyperalgesia were different from normal skin (107.5 g; 101.5, 115.2). This model clearly showed the antihyperalgesic effect of both systemic and topical ibuprofen (42.1%; 26.6, 61.2 and 33.8%; 16.4, 51.2 of MPT increase, respectively) but not that of acetaminophen. Conclusion: Cutaneous freeze injury coupled with a von Frey electronic device to assess the mechanical pain threshold is a convenient model that causes no discomfort. The improved sensitivity and stability of this experimental model of hyperalgesia over three consecutive days make it a useful tool for evaluating the efficacy and detecting the potential sites of action of analgesic agents such as nonsteroidal anti-inflammatory drugs in healthy human subjects.
BIOSEB Instruments Used
Electronic Von Frey 4 (BIO-EVF4),Electronic Von Frey 5 with embedded camera (BIO-EVF5)
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A quick solution to determine the mechanical sensitivity threshold in rodents (mice and rats). Now wireless, to be free from annoying cables!

This precise and easy-to-use electronic instrument is a must-have reference for your research in analgesia, nociception, neuro-pathologies and post-operative pain.

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The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.

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