Pre-emptive Infiltration of Lidocaine Reduces Formalin Pain Behavior in Rat

Song, Sun Ok; Park, Dae Pal; Kim, Heung Dae; Koo, Bon Up; Suh, Il Sook; Kim, Sae Yeon; Jee, Dae Lim; Suh, Bong Ho

Abstract

Surgical tissue damage induces dual phenomenon of peripheral and central sensitization. Postoperative pain could be partially explained by neuronal hyperexcitability. As a postoperative pain model, formalin test, subcutaneous injection of formalin in the rat hind paw, results in initial vigorous flinching(phase 1), depends on acute chemical stimulation, followed by cessation of activity, and then resumption of flinching(phase 2), which depends on central sensitization. Pre-emptive analgesia, given before the onset of a painful stimuli, reduces or ptevents postoperative pain by preventing this central sensitization. This study was performed to evaluate the effect of local infiltration of lidocaine as a pre-emptive analgesia in the formalin test. Forty experimental rats were divided four groups; CONTROL group(without any treatment), POST group(0.04 mL of 1% lidocaine injection 5 min after formalin injection), PRE group(0.04mL of 1% lidocaine 5 min before formalin injection), and SHAM group(injection of normal saline 5 min before formalin injection). All animals received inhalation anesthesia for 15 min before and 5 min after formalin injection. Under halothane inhalation anesthesia, all were injected subcutaneously 0.04 mL of 5% formalin in the distal plantar area of right hind paw. After recovery of anesthesia, the formalin-induced flinching behavior was observed during only the phase 2 period(10-60 min) after formalin injection. The time to first flinching, the mean number of flinches per min, and the mean number of total flinches during phase 2 expressed as a percent of the values of the CONTROL group were compared between the groups with an t-test or an ANOVA. The first flinching was appeared before recovery of anesthesia in CONTROL and SHAM groups. The time to first flinching after formalin injection was 21.2+/-3.4, 16.6+/-3.1 min respectively in PRE and POST groups. It was significantly longer in PRE group than in POST group(P<0.05), despite of 10 min earlier injeetion of lidocaine in PRE group. The mean number of flinches per min was significantly lower in PRE and POST groups(P<0.05) until 25 min after formalin injection, and after that time the difference between PRE group and POST group was significant(P<0.05). The means of the total number of flinches during phase 2, expressed as a percent of the values of the CONTROL poup, were 100+/-17.2%, 31.8+/-13.1%, 76.9+/-14.5% respectively in SHAM, PRE and POST groups. Those in PRE and POST groups were significantly lower than that of CONTROL group(P<0.001), and the difference between PRE group and POST group was significant(P<0.05). In summary, pre-emptive infiltration of lidocaine on formalin test prolongs the duration of analgesia and reduces the severity of formalin pain in rat. Therefore, the infiltration of lidocaine before formalin test is really provided pre-emptive analgesia.