• Journal of Yeungnam Medical Science
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• v.17 no.1
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• pp.12-20
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• 2000

The memory of pain can be more damaging than its initial experience. Several factors arc related the directions of pain memory: current pain intensity, emotion, expectation of pain, and peak intensity of previous pain. The possible mechanisms behind the memory of pain are neuroplastic changes of nervous system via peripheral and central sensitization. Peripheral sensitization is induced by neurohumoral alterations at the site of injury and nearby. Biochemicals such as K+, prostaglandins, bradykinin, substance P, histamine and serotonin, increase transduction and produce continuous nociceptive input. Central sensitization takes place within the dorsal horn of spinal cord and amplifies the nociceptive input from the periphery. The mechanisms of central sensitization involve a variety of transmitters and postsynaptic mechanisms resulting from the activations of NMDA receptors by glutamate. and activation of NK-1 tachykinnin receptors by substance-P and neurokinnin. The clinical result of peripheral and central sensitization is hyperalgesia, allodynia, spontaneous pain, referred pain, or sympathetically maintained pain. These persistent sensory responses to noxious stimuli arc a form of memory. The hypothesis of preemptive analgesia is that analgesia administered before the painful stimulus will prevent or reduce subsequent pain and analgesic requirements in comparison to the identical analgesic intervention administered after the painful stimulus, by preventing or reducing the memory of pain in the nervous system. Conventionally, pain management was initiated following noxious stimuli such as surgery. More recently, however many have endorsed preemptive analgesia initiated before surgery. Treatments to control postsurgical pain are often best started before injury activates peripheral nociceptors and triggers central sensitization. Such preemption is not achieved solely by regional anesthesia and drug therapy but also requires behavioral interventions to decrease anxiety or stress. Although the benefit of preemptive analgesia may not be obvious in every circumstance, and in many cases may not sufficient to abolish central sensitization, it is an appropriate and human goal of clinical practice.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.70-74
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• 1999

Background: Preemptive analgesia has been suggested recently as an another technique of postoperative pain control. Combination of low dose opioid and NSAIDs was used to lessen systemic opioid side effect, however, the use of NSAIDs may hinder their side effects in perioperative period. The local application of small dose at the target site can be effective without systemic effect. The aim of this study is evaluating the additive effect and side effect of transdermal piroxicam as preemptive adjuvant to intravenous nalbuphine on pain relief after major abdominal surgery. Methods: We reviewed the records of patients received piroxicam patch for preemptive analgesia before operation and compared it with control group. Two sheets of piroxicam patch to the skin incision site for 12 hours before operation were attached (Group 1, n=20) and no patch were applied (Group 2, n=20). Both groups were received nalbuphine continuously after operation using two days infuser (2 ml/hr) containing 80 mg (96 ml). Pain is evaluated by VAS score at each time; 30 min, 1, 6, 12, 24, 36, 48 hours after operation and side effects of NSAIDs were observed for 3days postoperatively. Results: There was no significant VAS score difference between two groups following time in progress. And no significant side effect was noted in both groups, either. Conclusion: There is no preemptive or synergistic analgesic effect of piroxicam patch attached at planned operation site before operation.

• Journal of The Korean Dental Society of Anesthesiology
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• v.3 no.1 s.4
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• pp.10-18
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• 2003

Background: Studies on the pain have been dealing with many different ways for last several centuries. Especially, preemptive analgesia is being used as a method to control the postoperative pain. Many studies on its efficacy have been processed in different ways about various drugs, administration methods and times for various operations. And the value of preemptive analgesia are still controversial regarding the results of other clinical studies. The authors performed a clinical study on efficacy of preemptive analgesia using an non-steroidal anti-inflammatory drug (NSAID) for the surgical extraction of impacted third molar teeth and present the more effective pain treatment after oral surgery with literature review. Methods: Using a randomized double blind test design, this study compared the analgesic efficacies of an NSAID, Talniflumate 370 mg. This drug administrated first either 1 hour preoperatively (experimental group) or when the pain developed moderately to severely over 5 scale of verbal rating scales (0-10) to respective 30 patients undergoing the removal of impacted third molars. Pain intensity and the time from the end of surgery were assessed postoperatively whenever the patients demanded additional drug over 5 scale for forty eight hours using same verbal rating scales. Results: The sex distribution, the age of the patients. and the time required for surgery in two groups were similar. The average first time for demanding additional drug after surgery was 163.9 minutes in experimental group and 191.5 minutes in control group. At this time, the average pain intensity was 5.8 in experimental group and 6.1 in control group. And the average second time for demanding additional drug was 365.5 minutes in experimental group and 351.8 minutes in control group. At this time. the average pain intensities were 6.6 in experimental group and 6.2 in control group. No statistically significant difference was found between the average first times and second times, and the average pain intensities at first and second times in two groups. Conclusions: From these results the efficacy of preemptive analgesia used in this study was not appeared. This clinical study indicates that many NSAIDs administrated preoperatively in present practices have weak efficacy of preemptive analgesia for postoperative pain, thus the authors recommend that only postoperative analgesics are adequate without preoperative use of analgesics.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.331-341
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• 2018

The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

• The Korean Journal of Pain
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• v.13 no.1
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• pp.38-43
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• 2000

Background: Preemptive analgesia may decrease postoperative pain by preventing nociceptive inputs generated during surgery. The preemptive effect of intravenous nalbuphine was examined in gynecological surgery. Methods: Forty female patients scheduled for gynecological surgery were randomly allocated into two groups. Each patient received 10 mg of intravenous nalbuphine as a bolus dose at the closure of peritoneum in group I (n=20) and before the skin incision in group II (n=20). After the bolus dose, the intravenous patient controlled analgesia (IV-PCA) which contained 50 mg of nalbuphine, 120 mg of ketorolac, 0.25 mg of droperidol and 90 ml of 5% dextrose water was given continuously at the rate of 2 ml/min. The postoperative visual analogue scale pain score (VAS), the total amount of the analgesics used, the degree of satisfaction of the patients and the developement of side effects were examined for 2 days. Results: VAS were significantly lower in group II than in group I after 9 and 12 hours. The cumulative consumption of analgesics in group II was significantly less than in group I. Most patients were satisfied with this regimen. There were no remarkable side effects. Conclusions: Preemptive analgesia with intravenous nalbuphine decreased postoperative pain and analgesic requirement. The analgesic effect of IV-PCA with nalbuphine-ketorolac was effective in control of postoperative pain in gynecologic surgery.

• The Korean Journal of Pain
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• v.10 no.2
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• pp.185-190
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• 1997

Background: Preemptive analgesia is an antinociceptive treatment that prevents the establishment of altered central processing which amplifies postoperative pain. A controversy exists over the effectiveness and clinical value of preemptive analgesia. We studied whether epidural bupivacaine and fentanyl prior to surgery could possibly affect postoperative pain and analgesic demands, as compared to administration of same at end of surgery. Methods: Forty patients scheduled for lower abdominal surgery were randomly assigned to one of two groups and prospectively studied in a double-blind method. Group 1(n=20) received epidural injection of 15 ml bupivacaine 0.25% with fentanyl 100 y g before surgery while group 2(n=20) received the same injection at the end of their surgery respectively. Postoperative analgesia consisted of basal plus patient-controlled mode of epidural bupivacaine and fentanyl from PCA system. Postoperative visual analog pain scores(VAPS), analgesics consumption, supplementary analgesics requirement and side effects were assessed for 3 postoperative days. Results: There were no significant difference in analgesics requirement and pain scores, at any time, during rest or after movement, in measurement between the groups. Conclusions: We conclude no clinical value of effectiveness in administering epidural bupivacaine-fentanyl before surgery as compared to administration after surgery.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.165-170
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• 2005

Background: It is difficult to treat tourniquet-induced hypertension despite adequate anesthesia, and the mechanism of that is not known. And it may be possible that intraoperative continuous infusion of opioid induces preemptive analgesia postoperatively. We investigated the effect of intraoperative continuous i.v. fentanyl on tourniquet induced cardiovascular changes and postoperative preemptive analgesia in total knee replacements. Methods: Sixty patients were randomly assigned to two groups; In study group ($1.5{\mu}g/kg$ loading and $0.5{\mu}g/kg/hr$ continuous infusion of fentanyl before skin incision and tourniquet inflation) and control group (no treatment). Anesthesia was maintained with enflurane (1-2 MAC) and 50% nitrous oxide in oxygen. Arterial pressure and heart rate were compared between two groups. They received postoperative pain treatment with patient-controlled analgesia (PCA) with fentanyl during the postoperative 48 hours after total knee replacement. Visual analog scale (VAS) scores at either rest or movement were used to assess pain. Total fentanyl dose delivered, number of PCA requests, supplemental analgesics, overall satisfaction score and adverse events were evaluated. Results: There were no significant differences between the two groups on cardiovascular changes by tourniquet induced pain effect. VAS, PCA delivered dose and PCA demands at movement in the 24-48 hour decreased in study group compared with control group (P < 0.05). But there were no significant differences between the two groups on the other time periods except 24-48 hour's patient satisfaction and adverse events. Conclusions: We suggest that intraoperative continuous i.v. fentanyl infusion dose not affect cardiovascular change by tourniquet induced pain. But it may induce preemptive analgesia postoperatively.

• Journal of The Korean Dental Society of Anesthesiology
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• v.4 no.2 s.7
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• pp.84-89
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• 2004

Background: Many studies on efficacy of preemptive analgesia have been processed in different ways. But the value of preemptive analgesia is still controversial. The goal of this study was to compare analgesic effect of an NSAID according to three different administration times for oral surgical pain. Patients and Methods: Using a randomized, parallel-group, single-center, and active-controlled test design, this study was conducted to healthy 80 patients undergoing a surgical removal of an impacted mandibular third molar requiring bone removal. The oral NSAID was first administered 1 hour preoperatively, or 1 hour postoperatively, or no scheduled administration in pre or postsurgery. Whenever patients felt at least moderate pain (score ${\ge}$ 5 on a 10-point scale) after surgery, they were instructed to take the same drug. Pain intensities and times to the first and second onset of postoperative pain from end of surgery were assessed for 24 hours. Results: Of the enrolled eighty subjects in this study, 25 patients were assigned to preemptive, 26 to post-treatment and 29 to no treatment group. The demographic distribution and duration of surgery in the three groups were statistically similar. The mean time to first onset of postoperative pain was significantly prolonged in post-treatment group (277.2 minutes, p < 0.05) compared to preemptive (158.4 minutes) and no treatment group (196.5 minutes). The mean time to second onset of postoperative pain was not significantly different among the three groups. No significant statistical difference was found among the mean pain intensities at the first and second onset of postoperative pain in the three groups. Conclusions: In this small selected group of subjects and limited study design, the analgesic effects of NSAID administered preoperatively were no longer effective for postoperative pain. The results in this population imply that scheduled postoperative analgesics before pain development are adequate for postoperative analgesia without preoperative administration.

• The Korean Journal of Pain
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• v.19 no.2
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• pp.218-222
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• 2006

Complex regional pain syndrome (CRPS) is a syndrome of pain and sudomotor or vasomotor instabilities. The perioperative pain management in CRPS patients is very important, as surgery can aggravate preexisting symptoms, especially when performed around the lesion site. Despite the increasing interest in CRPS research, little is known about the optimal perioperative treatment strategy for CRPS patients. Herein, the case of a female CRPS patient, who underwent elective surgery at the lesion site, is reported. As a preemptive analgesia, the patient was satisfactorily managed with two weeks of patient-controlled epidural analgesia, initiated 2 days prior to surgery. The techniques for the prevention of perioperative pain, including preemptive analgesia, as well as its importance, are discussed.

• The Korean Journal of Pain
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• v.24 no.3
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• pp.137-140
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• 2011

Background: Although early reviews of clinical findings were mostly negative, there is still a widespread belief for the efficacy of preemptive analgesia among clinicians. In this study, we evaluated whether the preemptive use of ketamine decreases post operative pain in patients undergoing appendectomy. Methods: In double-blind, randomized clinical trials, 80 adult male patients undergoing an operation for acute appendicitis were studied. Patients were randomly assigned to two groups. In the operating room, patients in the ketamine group received 0.5 mg/kg of ketamine IV 10 minutes before the surgical incision. In the control group, 0.5 mg/kg of normal saline was injected. The pain intensity was assessed at time 0 (immediately after arousal) and 4, 12, and 24 hours postoperatively using the 10 points visual analogue scale (VAS). Results: Eighty patients (40 for both groups) were enrolled in this study. For all of the evaluated times, the VAS score was significantly lower in the ketamine group compared to the control. The interval time for the first analgesic request was $23.1{\pm}6.7$ minutes for the case group and $18.1{\pm}7.3$ minutes for the control (P = 0.02). The total number of pethidine injections in the first 24 hours postoperatively was $0.6{\pm}0.6$ for the case group and $2.0{\pm}0.8$ for the controls (P = 0.032). There were no drug side effects for the case group. Conclusions: A low dose of intravenously administered ketamine had a preemptive effect in reducing pain after appendectomy.