D. Fletcher et al., INFLUENCE OF TIMING OF ADMINISTRATION ON THE ANALGESIC EFFECT OF BUPIVACAINE INFILTRATION IN CARRAGEENAN-INJECTED RATS, Anesthesiology, 84(5), 1996, pp. 1129-1137
Background: Recent evidence has suggested that the timing of administr
ation of analgesic drugs could influence their efficacy by reducing th
e sensitization of the nervous system induced by the nociceptive input
s, but this concept of preemptive analgesia is still debated in both c
linical and basic research. Methods: The model of acute inflammatory p
ain induced by carrageenin was used to study the influence of timing o
f administration of bupivacaine (0.2 ml of a 0.5% solution with 0.005
mg/ml epinephrine) on the development of hyperalgesia, edema, and incr
ease in temperature, The animals received bupivacaine 5 min before (BU
PI PRE group, n = 20) or 60 min after (BUPI POST group, n = 20) carrag
eenin (1 ml/kg of 1% solution) was injected into the left hind paw. Tw
o control groups (n = 15 in each) received saline 5 min before or 60 m
in after administration of carrageenin. Hyperalgesia of the injected p
aw was evaluated by the vocalization threshold to paw pressure, edema
by measuring paw circumference with a thread, and plantar temperature
with a thermocouple thermometer. All measurements were done before car
rageenin injection then every 30 min thereafter for 240 min. Another s
eries (n = 24), with the same four groups was also evaluated at 24 h.
Results: Local injection of bupivacaine 60 min after carrageenin parti
ally reduced the edema and hyperalgesia, The Injection of bupivacaine
5 min before carrageenin was more efficient than the delayed injection
and reduced hyperalgesia, edema and the increase in temperature tempo
rarily, but did not totally prevent their development, All groups were
similar at 240 min and 24. Conclusions: These results show that a sli
ght advantage of infiltration with bupivacaine before injury exists in
this carrageenin model of acute inflammatory pain. However, this bene
fit is limited in time and bupivacaine did not have any preemptive ana
lgesic effect.