The formalin test: A quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats

Abstract

A method for assessing pain and analgesia in rats and cats is described. The procedure involves subcutaneous injection of dilute formalin into the forepaw, after which the animal's responses are rated according to objective behavioral criteria. The formalin test is a statistically valid technique which has two advantages over other pain tests: (1) little or no restraint is necessary, permitting unhindered observation of the complete range of behavioral responses; and (2) the pain stimulus is continuous rather than transient, thus bearing greater resemblance to most clinical pain. The analgesic effects of morphine, meperidine, and stimulation of the periaqueductal grey matter are evaluated using this test.

Antinociceptive effect of a genomic herpes simplex virus-based vector expressing human proenkephalin in rat dorsal root ganglion

“…Injection of dilute formalin subcutaneously into the footpad of control animals caused the rats to exhibit nocifensive behaviors as previously described, 22 with an immediate pain response (at time 0), a period of normal behavior (observed at 10 min after formalin injection), followed by a characteristic increasing and than decreasing pain response lasting over 60 min (Figure 3a, control curve -filled circles). Rats injected with SHPE 1 week before formalin testing showed a significant reduction in nocifensive behaviors at 30, 40, 50, 60, and 70 min after formalin injection (Figure 3a, black squares).…”

“…The formalin test 22 allows the observation of nocifensive behaviors in unrestrained animals over a prolonged period of time. Human subjects describe the pain caused by formalin injection as an initially intense, sharp or stinging sensation that gives way to a steady throbbing ache that gradually disappears over 1 h. 22 The response recorded in the 'tonic' phase in animals corresponds to that steady throbbing ache, in contrast to acute pain sensation.…”

“…22 A dilute solution of formalin (2.5%) was injected subcutaneously in the plantar aspect of the same foot that had received the viral inoculation, and the rats then placed into a 48 × 27 × 20 cm plastic box positioned over a mirror tilted at a 45°angle. Beginning 30 s after the injection of formalin, and once every 10 min thereafter, nocifensive behaviors were recorded by a blinded observer for 3 min; a weighted pain score was derived based on the amount of time the animal exhibited each behavior during the 3 min period of observation.…”

Effects of pedunculopontine tegmental nucleus lesions on morphine-induced conditioned place preference and analgesia in the formalin test

“…Developed by Dubuisson and Dennis (1977) as an animal model of clinicul pain, the procedure involves injecting of a small quantity (0.05 ml) of dilute formalin into the animal's paw and assessing its protective responses towards the injured limb. Human subjects who have experienced the pain of formalin injection describe it as initally burning in quality, then developing into a deep aching pain that recedes over 90 minutes.…”

Lentiviral vector‐encoded microRNA‐based shRNA‐mediated gene knockdown of N‐methyl‐D‐aspartate receptors in skin reduces pain

“…The formalin test is a widely used model of prolonged noxious stimulation (Dubuisson & Dennis, 1977). Several studies addressed the essential role of afferent input from the periphery in generating and maintaining nociception in the second phase of the formalin test (Dickenson & Sullivan, 1987; Pitcher & Henry, 2002).…”