EFFECTS OF PREEMPTIVE OR POSTINJURY INTRATHECAL LOCAL-ANESTHESIA ON PERSISTENT NOCICEPTIVE RESPONSES IN RATS - CONFOUNDING INFLUENCES OF PERIPHERAL INFLAMMATION AND THE GENERAL ANESTHETIC REGIMEN

Background: Although experimental evidence indicates that preemptive i ntrathecal treatment with local anesthetics reduces postinjury neurona l hyperexcitability, clinical evidence indicates that preemptive treat ments do not consistently reduce postoperative pain. The current study used experimental models of postinjury nociception, in which rats rec eived subcutaneous or intraarticular injections of the irritant formal in, to evaluate the effects of peripheral inflammation, or the use of agents supplemental to anesthesia, as possible confounding influences on the effectiveness of preinjury and postinjury intrathecal local ane sthetic treatments. Methods: In experiment 1, lumbar intrathecal lidoc aine (30 mu l, 2%), given either 5 min before or 5 min after hind paw injection of 50 mu l of varying concentrations of formalin, was compar ed with intrathecal cerebrospinal fluid, for their effects on nocicept ive responses in the late phase of the formalin test. Furthermore, the effect of hind paw injection of 50 mu l of 2.5, 3.75, or 5.0% formali n on peripheral inflammation was assessed by measuring plasma extravas ation in the hind paws of rats given Evans Blue dye (50 mg/kg, intrave nous), In experiment 2, rats received a deep tissue injury (100 mu l o f 5.0% formalin into the knee joint) while under halothane anesthesia, In addition to halothane (3-4%), rats received either saline, pentoba rbital (13 mg/kg, intraperitoneal), or pentobarbital + morphine (0.5 m g/kg, intravenous), with or without preinjury or postinjury spinal ane sthesia using intrathecal bupivacaine (30 mu l, 0.75%), to assess the effects of supplemental treatments on the preemptive effects of intrat hecal bupivacaine. Results: Lumbar intrathecal lidocaine pretreatment, but not posttreatment, significantly reduced late phase nociceptive r esponses to hind paw injections of 2.5% formalin. The preemptive effec ts of lidocaine were overridden in rats that received hind paw injecti ons of 3.75 and 5.0% formalin, Hind paw injection of 50 mu l of 3.75 o r 5.0%, but not 2.5% formalin produced an increase in plasma extravasa tion. Either pentobarbital or pentobarbital + morphine treatment, or a pentobarbital + morphine treatment and postinjury treatment with intr athecaal bupivacaine failed to produce a significant reduction in the nociceptive response to the deep tissue Injury, However, rats that rec eived pentobarbital + morphine treatments and intrathecal bupivacaine before the injury had significantly reduced nociceptive responses to d eep tissue injury when compared to the saline control group, but not t o the group that received pentobarbital + morphine treatment and posti njury treatment with bupivacaine. Conclusions: The current results att est to the important effects of ongoing inputs from inflamed tissue, a nd the use of supplemental treatments, as important confounding factor s that may influence the effectiveness of preemptive spinal anesthesia for postoperative pain.