The Formalin Test: Characteristics and Usefulness of the Model (original) (raw)

The formalin test was introduced as a model of tonic pain in 1977, and has since been used extensively in rats and mice. In rats, formalin generates an initial phase of activity (5–10 min, phase 1), a quiescent interphase (5–10 min), and a second phase of activity (lasting 60–90 min, phase 2), and this is seen with spontaneous behaviors, firing of afferent neurons, and activity in dorsal horn neurons. Both active phases involve ongoing peripheral afferent neural activity; inflammation contributes to phase 2 activity and the interphase results from active inhibition. Responses are concentration dependent between 0.25% and 2.5%, plateau from 2.5% to 5%, and can decline at higher concentrations. Formalin also results in tissue edema, and this is longer lasting. Responses to formalin up to 2.5% are predominantly neurogenic, while at higher concentrations, responses involve a further prominent inflammatory component. Within the spinal cord, formalin increases c-Fos expression in neurons and causes activation of microglia, and these may contribute more prominently to longer term changes. Acute responses (to 90 min) may represent a model of ongoing acute pain involving inflammation and aspects of central sensitization, while longer term responses (days, weeks) may represent a model of changes involved in persistent pathological pain.

Keywords: Acute responses;Central sensitization;Formalin test;Long-term responses;Pain model;Peripheral afferent neural activity;Phase activity

Document Type: Research Article

Affiliations: 1: *Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4H7 2: †University of Toronto, Hospital for Sick Children, Brain and Behavior, McMaster Building, 555 University Avenue, Toronto, Ontario, Canada M5G 1X8

Publication date: 2003-01-01

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