The influence of the timing of bupivacaine infiltration on the time course of inflammation induced by two carrageenin injections seven days apart

The mechanical allodynia and edema related to a subcutaneous carrageenin injection are increased by a conditioning carrageenin injection 7 days before (Guilbaud et al., 1992). In the present study, the possibility of preventing this by bupivacaine infiltration was tested. In the first part of the experiment, the time course of a carrageenin induced inflammation of the right hind paw was assessed in animals receiving local anesthetic injection (0.2 ml of bupivacaine 0.5% solution with epinephrine) either 5 min before (BUPI PRE group) or 60 min after (BUPI POST group) the carrageenin injection (0.2 ml of 1% solution). Control groups received saline (0.2 ml) with the same timing. In the second part of the experiment, 7 days later, a carrageenin injection was performed either in the right or the left hind paw. Mechanical allodynia and edema were evaluated by the vocalization threshold to paw pressure (VTPP) and paw circumference (PC) in both hind paws at 1, 2, 4, 24 h and 7 days after both carrageenin injections. The first carrageenin injection induced mechanical allodynia and edema maximal at 240 min (42% reduction of VTPP; 23% increase in PC) and the influence of bupivacaine on the VTPP and PC was similar to previous results (Fletcher et al., 1996). The second ipsilateral carrageenin injection induced a more pronounced inflammation in the control groups and BUPI POST group than the first injection (P < 0.001). In contrast, the increase in allodynia and edema was less intense in the BUPI PRE group than in the other groups (P < 0.0001 and P < 0.02 respectively). Bupivacaine injections had no effect on allodynia and edema related to a second contra-lateral carrageenin injection. These results suggest that bupivacaine infiltration, when administered before the first conditioning injection of carrageenin, can prevent the reinforcement of mechanical allodynia and edema related to a second ipsilateral injection of carrageenin 7 days later.