Effects of Different Concentrations of Formalin on Paw Edema and Pain Behaviors in Rats

Abstract

The aim of this study was to determine whether formalin reliably provokes a paw edema and pain behavior. The paw of male Sprague-Dawley rats were injected with 100 microliter of formalin with 2.5% (F2.5), 5% (F5), and 10% (F10) concentrations. Following the formalin (n=8) or saline (control, n=6) injection, the flinching or licking of the paw was recorded for the phase 1 response (0-5 min after injection) and phase 2 response (20-60 min). The formalin-induced paw edema was assessed by measuring the diameters of the injected paws at 4 hr after injection. As for flinching, phase 1 and 2 of all three groups showed higher frequency than those of the control group (p<0.05). As for licking, phase 1 cumulative time of the F2.5 and F10 groups, and phase 2 cumulative time of the F2.5 and F5 groups showed a longer duration than those in the control group (p<0.05). The diameters of the paw in the F10 group were significantly larger than those in the control group (p<0.05). Flinching behavior was more reliably expressed the biphasic response than licking response at all formalin concentrations. Peak of the licking was reached at 2.5% and that of flinching was reached at 5%, whereas the paw edema peaked at 10% concentration. This suggests that there may be some dissociation of nociception from the edema formation.

Leukocyte Recruitment to Peritoneal Cavity of Rats Following Formalin Injection: Role of Tachykinin Receptors

“…In this model, formalin is able to acutely affect peripheral sensory nerve endings (5), with subsequent release of mediators, which give rise to a biphasic painful response (3,16). However, when Dubuisson and Dennis (1) first described this response, they had also observed that inflammation (edema) was a prominent feature accompanying the painful response, later confirmed by others (4,17).…”

Antinociceptive Activity of Methanolic Stem Bark Extracts of Harrisonia Abyssinica Oliv and Landolphia Buchananii (Hallier F.) Stapf in Mice Model

“…A formalin concentration of 2.5-5% is a better dose than 10% because it evokes maximal responses [20]. In fact, the 10% formalin is not recommended for a pain test.…”

Antinociceptive and Anti-inflammatory Activities of Methanol Extract of Ormosia coccinea (Aubl.) Jacks in vivo

“…Substance P, glutamate and bradykinin are thought to participate in this phase, which is believed to be non-inflammatory pain [28]. The second phase, commonly denominated late or inflammatory phase (from 15 a 30 min) [29] is associated with the release of local endogenous mediators (histamine, serotonin, prostaglandins and bradykinin) responsible for sensitization of primary and spinal sensory neurons and subsequent activation of the nociceptor [20,25,34]. It is well established that both phases of the formalin test can be inhibited by centrally acting drug, such as narcotics, whereas peripherally acting drugs, such as acetylsalicylic acid, only inhibit the second phase [21,22,29,30].…”

“…Intraplantar injection of formalin has been reported to produce a distinct biphasic nociceptive response [12,21], termed first and second phases [20]. The first phase, commonly denominated early or neurogenic phase (from 0 to 5 min after injection formalin) results from a direct stimulation of nociceptors (predominantly C-fibres) [22,23,27,28,31,32,34]. Substance P, glutamate and bradykinin are thought to participate in this phase, which is believed to be non-inflammatory pain [28].…”