In Vivo Pain Models - Analgesic Efficacy Testing - Animal Models for Nociception - Formalin Test, Hargreaves Test, Von Frey Fibers


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Nociceptive Models

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In Vivo Models for Study of Analgesic Efficacy of Test Compounds

Our In Vivo tests for analgesic effects of test materials include mouse and rat models for thermal, mechanical, and chemical stimuli (1). Basic models for thermal and mechanical pain responses may also be combined with inflammation models to provide information on analgesic activity in inflamed tissue.

Formalin Test (Chemical Sensitivity):

The most predictive of the models for acute pain is the Formalin Test. In this widely used model a 5% solution of formaldehyde is injected subcutaneously to mouse or rat paw to produce a biphasic pain response over a test period of 60 minutes. The initial pain response occurs at 1 minute following subplantar injection of formalin and results from direct stimulation of nociceptors. The second phase of pain response occurs after a period of sensitization (quiescent period) during which inflammatory phenomena take place (2). Opiod analgesics appear to be antinociceptive for both phases. NSAIDS such as indomethacin appear to suppress only the second phase (3).

Pain response scoring includes counts per unit of time of reactions to the pain stimulus by licks, twitches, raising or shaking of the injected paw.

Hargreaves Test (Thermal Sensitivity):

The Hargreaves Method uses mild radiant heat to measure thermal nociception in cutaneous hyperalgesia (4,5). The time for foot withdrawal response characterizes the pain response measurement.

This method combined with the Randall-Selitto method (6) for measurement of analgesic activity in inflamed tissue can be used to study hyperalgesic phenomena in in vivo models of inflammation where the inflammation is produced by chemical agents such as carrageenan.

Von Frey Fibers (Mechanical Sensitivity):

A valuable and widely used tool for investigating chronic pain uses so-called von Frey fibers to apply pressure to the skin of test animals. Fibers of defined diameters are applied which when made to bend produce a constant pressure which increases with increasing diameter of the applied fiber (6). The preferred sites for applying nociceptive mechanical stimuli are the hind paw and the tail.

Nociceptive studies in mice or rats at Washington Biotechnology can usually be scheduled to begin within 2 weeks of your order. Custom studies combining pain models with other models such as inflammation models (arthritis, carrageenan paw edema, diabetes, etc.) can be arranged through consultation with our technical staff.

References.

1.      Le Bars D, Gozariu M and Cadden SW (2001). Animal Models of Nociception. Pharmacol Rev 53: 597-652.

2.      Dubisson D and Dennis SG (1977). The Formalin Test: A Quantitative Study of the Analgesic Effects of Morphine, Merperidine and Brain Stem Stimulation in Rats and Cats. Pain 4:161-174.

3.      Jourdan D, Ardid D, Bardin L, Bardin M, Neuzeret D and Lanphouthacoul L (1997). A New Method of Pain Scoring in the Formalin Test in Rats. Pain 71:265-270.

4.      Hargreaves K, Dubner R, Brown F, Flores C and Joris J (1988). A New and Sensitive Method for Measuring Thermal Nociception in Cutaneous Hyper alagesia. Pain 32:77-88.

5.      Yeomans DC and Proudfit HK (1994). Characterization of the Foot Withdrawal Response to Noxious Radiant Heat in the Rat. Pain 59:85-94.

6.      Handerwerker HO and Brune K (1987). Classical German Contributions to Pain Research. Tagblatt-Druckerei KG, Hassfurt.