| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1994: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
Recent evidence has suggested that the timing of administration of analgesic drugs influences their efficacy by reducing the sensitization of the nervous system induced by nociceptive inputs. The intensity of postoperative pain may be reduced by preadministration of drugs like local anesthetics or opioids leading to the concept of preemptive analgesia. However, this concept is still debated. The purpose of this study is to clarify the evidence of preemptive analgesia in clinical and laboratory investigations.
Clinical investigation : 1)Ninety patients undergoing abdominal hypterctomy were allocated to three groups : 30 patients of group 1 with general anesthesia alone, 30 patients of group 2 with epidural analgesia 20 min before the end of surgery under general anesthesia, and 30 patients of group 3 with epidural analgesia plus general anesthesia before surgery. Immediately after surtery, 5 ml of the mixture of 0.225% bupivacaine and 0.0005% fentanyl was injected epidurally and followed
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with continuous infusion of the same mixture at the rate of 2.1 ml/h over 24 h. Visual analogue score and Prince-Henry score were significantly less in group 3 than in groups 1 and 2 at 4 and 24 h after surgery. 2)Forty-one patients were divided into two groups : 21 patients of an epidural group received 0.2 mg of fentanyl epidually and 20 patients of an intravenous group received 0.2 mg of fentanyl intravenously. Postoperative pain was managed with the same method above. Prince-Henry score was significantly less in the epidural group than in the intravenous group at 24 and 48 h after surgery.
Laboratory investigation : After pentobarbital anesthesia, 150 mu 1 of 5% formalin solution was injected subcutaneously into the plantar surface of the right hindpaw. Fentanyl (0.001,0.01,0.1 or 0.5 mu g in 10 mu1) was injected in the subarchnoid space through the catheter placed 1-2 weeks ago, 15 min before (pretreatment), 5 min after (early posttreatment) or 60 min after formalin test (later posttreatment). Lidocain (0.3 or 0.75 mg in 15 mu 1) was also injected intrathecally 10 min before, 5 min after or 60 min after formalin test. Two h later from formalin test, the rats were re-anesthetized with pentobarbital and perfused transcardially with 4% paraformaldehyde. The spinal cord at the lumbar enlargement was removed and post-fixed. Fifty mu m frozen sections were cut in the transverse plane and reacted with polyclonal anti-c-Fos antiserum. The streptavidin-biotin-horseradish peroxidase method was employed to visualize the c-Fos immunoreactive nuclei. Numerous c-Fos like immunoreactive (c-Fos LI) neurons were observed in lawinae I and II,and laminae V and VI of the L4 AND L5 spinal cord, ipsilateral to the formalin-injected hindpaw. Pretreatment with fentanyl or lidocaine decreased significantly dose-dependently c-Fos LI neurons. The reduction of c-Fos LI neurons by fentanyl was significantly greater in laminae V and VI than in laminae I and II.The significant reduction was also observed follwing early posttreatment with fentanyl or lidocaine, although it was significantly less than the reduction following pretreatment. However, no reduction was found following later posttreatment with fentanyl or lidocaine.
Our results of laboratory investigation demonstrated that fentanyl or lidocaine administered intrathecally before or immediately after formalin injection suppresses c-Fos expression in the spinal cord. Fentanyl or lidocaine suppressed strongly when it administered before formalin infection, compared with it administered immediately after formalin. An antinociceptive treatment with opioids or local anesthetics given before noxious stimuli is more effective in the suppression of c-Fos expression than the treatment given after noxious stimuli. Our results of clinical investigations suggested that continuous epidural analgesia after surgery is effective when noxious stimuli to the central nervous system during surgery are blocked by epidural local anesthetics or opioids. These evidence would support the concept of preemptive analgesia. Less
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