Systemic, but not Intrathecal, Ketamine Produces Preemptive Analgesia in the Rat Formalin Model

Systemic, but not Intrathecal, Ketamine Produces Preemptive Analgesia in the Rat Formalin Model

Background: We investigated the antinociceptive effects of pre- or posttreatment of intrathecal or intravenous ketamine on formalin-induced pain behaviors. Methods: Rats were divided into 4 groups of 7 rats each and 2 control groups (saline). Rats received ketamine 1 mg/kg intrathecally (i.t.) through a catheter either 15 min before or 5 min after formalin. In the other groups, they received ketamine 1 mg/kg intravenously (i.v.) through a catheter either 1 min before or 5 min after the formalin. Pain related behavior was quantified by counting the incidence of flinching of the injected paw for 60 min. Formalin induced a biphasic fliching (phase 1, 0 -5 min; phase 2, 10-60 min after formalin injection) of injected paw. The inter-group (control, pre, and posttreatment groups) comparisons were performed separately for route of administration (i.t. or i.v.) and phase 1 and 2 using one-way ANOVA and Tukey test. Results: Flinches of phase 1 were not different among the three i.t. groups. The total flinches of phase 2 were reduced by posttreatment with i.t. ketamine (P < 0.05); In contrast, i.v. ketamine was effective only when given as a pretreatment. Flinches of phase land 2 were reduced by pretreatment with i.v. ketamine (P < 0.05). Conclusions: Intrathecal ketamine was an analgesic even when administered as a posttreatment, whereas intravenous ketamine produced effective preemption only when given as a pretreatment.