The formalin test elucidates central and peripheral activities of
nociception. The response pattern has two distinct periods of
intensive licking activity, an early response (0–5 min after injection)
and a late response (20–30 min after injection). The early
phase is due to direct effect of formalin on nociceptors. The late
phase response is due to development of an inflammatory
response and release of analgesic mediators, which reflect inflammatory
pain (Hunskaar and Hole, 1987; Koster et al., 1959).
Different studies have indicated that substance P and bradykinin
participate in the early phase, whereas histamine, serotonin,