The formalin test: an evaluation of the method

Abstract

The formalin test for nociception, which is predominantly used with rats and mice, involves moderate, continuous pain generated by injured tissue. In this way it differs from most traditional tests of nociception which rely upon brief stimuli of threshold intensity. In this article we describe the main features of the formalin test, including the characteristics of the stimulus and how changes in nociceptive behaviour may be measured and interpreted. The response to formalin shows an early and a late phase. The early phase seems to be caused predominantly by C-fibre activation due to the peripheral stimulus, while the late phase appears to be dependent on the combination of an inflammatory reaction in the peripheral tissue and functional changes in the dorsal horn of the spinal cord. These functional changes seem to be initiated by the C-fibre barrage during the early phase. In mice, the behavioural response in the late phase depends on the ambient temperature. We argue that the peripheral tissue temperature as well as other factors influencing the peripheral inflammation may affect the response, possibly confounding the results obtained with the test. Furthermore, we discuss the methods of recording the response and the value of observing more than one aspect of behaviour. Scoring of several behavioural variables provides a means of assessing motor or sensorimotor function as possible causes for changes in behaviour. In conclusion, the formalin test is a valuable addition to the battery of methods available to study nociception.

p-Cymene reduces orofacial nociceptive response in mice

“…This phase is only sensitive to analgesics acting on the CNS (Hunskaar et al, 1985). The first phase is followed by an interphase, which lasts about fifteen minutes and results from active inhibition of the excitability of nociceptors (Tjolsen et al, 1992). The second phase, which starts twenty-one min after formalin injection, is derived from two components: central sensitization of nociceptors and second order neurons, and the action of inflammatory mediators such as histamine, serotonin (5-HT), bradykinin, and prostaglandins released as a result of tissue injury (Henry et al, 1999).…”

Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats

“…16,17 Recent evidence supports the presence of excitatory amino acid receptors on peripheral cutaneous axons, and subcutaneous formalin has been shown to induce the peripheral release of NO through activation of an NMDA-NO cascade in the peripheral nervous system. 18,19 In addition, opioids have been reported to act peripherally, and their importance is being increasingly appreciated.…”

The bioguided fractionation and pharmacological activity of an endemic Salix canariensis species

“…The first phase (0 to 5 min) results from direct stimulation of nociceptors. The second phase (15 to 30 min) is thought to be an inflammatory response with associated inflammatory pain, which is a process in which several inflammatory mediators are believed to be involved, including histamine, serotonin, prostaglandins and bradykinin (10). In this study, the inhibitory effects of S. canariensis extracts were more marked in the second phase, suppressing the pain in a dose-dependent manner, by 23.2, 32.5 and 42.1 % (p < 0.05), resp.…”