• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.555-563
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• 1999

It is well known that stress induces analgesia. This study was designed to demonstrate the stress-induced analgesia by employing hemorrhage and restraint and to investigate its mechanism and sex difference. The degree of pain was assessed by measuring the magnitude of jaw opening reflex produced by a noxious electrical stimulation in the dental pulp and by measuring the latency to withdraw the tail from a heat ray. Restraint showed an antinociceptive response. A significant increase in pain threshold on bleeding was shown and the increase was larger in male group than in female group. The tail flick latency (TFL) on bleeding after AVP antagonist injection into the ventricle was decreased and the decrease was greater in male rats than in female rats. Castration resulted in a significant reduction of TFL. This effect was reversed by treatment with sex hormones. TFL was decreased during hemorrhage in castrated rats. This response was opposite to that in non-castrated rats. TFL was further decreased during hemorrhage after infusion of AVP antagonist, and there was a significant sex difference. These results suggest that both restraint and hemorrhage produce an antinociception and that, in hemorrhage-induced analgesia, AVP and sex hormones may play an important role and male rats show a greater analgesic response.

• Journal of Ginseng Research
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• v.17 no.1
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• pp.22-28
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• 1993

This study was undertaken to determine the effects of ginseng total saponin (GTS) on stress- induced analgesia (SIA) in mice. intermittent foot shock (FS)-SIA was antagonized not by on but by naloxone in the tail flick FS-SIA which was not antagonized by naloxone in the T.F. test. On the other hand, GTS did not antagonize the continuous FS-SIA naloxone antagonized in the T.P. test. Also GTS antagonized psychological (PSIF)-SIA which was not antagonized by naloxone in the T.F. test. However, GTS did not antagonize the PSY-SIA which naloxone antagonized in the T.P. test. Forced swimming (FSIP)-SIA was not affected by both GTS and naloxone. These results suggest that the antapeonisms of intermittent FS-SIA in the T.F. test, continuous FS-SIA and PSY-SIA by GTS are mediated by non-opioid mechanisms but the antagonism of intermittent FS-SIA in the T.P. test by GTS is mediated by opioid mechanism.

• 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.

• Korean Journal of Acupuncture
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• v.25 no.3
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• pp.65-80
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• 2008

Objective : In recent years, many investigators have questioned whether the analgesic effect of acupuncture is simply related to the stress-induced analgesia (SIA). However, there has been lack of studies on this issue. In this study, the stress levels induced by manual acupunctures are compared with the stress in animal experiment models. The experiments have been carried out with Sprague Dawley (SD) rats. Method : For stress level evaluation, Hot plate test has been used. Maximum Possible Effect (MPE) has been measured by checking the pre-test time and post-test time. Cortisol and corticosterone concentrations in serum were measured by enzyme-linked immunosorbent assay (ELISA). Results : In the hot plate test, MPE values of post-test time were significantly decreased after 10 minutes than after 5 minutes. Therefore, optimal time interval was chosen as 10 minutes. There was significant difference of MPE values between Suspension group and all other treatment groups. However, there were no significant differences of MPE values between Sham group and all other treatment groups. However, MPE values showed tendency to decrease when acupuncture needle diameter increased. MPE values of ST040, ST040(lido), NAP040(lido) groups were markedly decreased than that of Suspension group, while that of NAP040 group was substantially increased than that of Sham group increased in acupoint and nonacupoint models. Serum cortisol concentrations of treatment groups were not significantly different from that of Suspension and Sham groups. Serum corticosterone concentration of 0.25 mm group was substantially increased than that of compared with Sham group. Serum cortisol and corticosterone concentrations of treatment groups were not significantly different from those of Suspension and Sham groups in acupoint and nonacupoint models. Conclusion : From hot plate test and serum stress hormones concentrations, it is found that manual acupuncture treatment induces negligible stress or SIA on ST36. And the stress induced by manual acupuncture is more closely related to acupuncture point needlings than diameters of acupuncture needles.

• Korean Journal of Psychosomatic Medicine
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• v.4 no.1
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• pp.124-137
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• 1996

As the society becomes more industrialized and modernized, we have more chances to experience a serious traumatic event. Post-traumatic stress disorder (PTSD) has 3 major categories of symptoms such as memory disturbance, hyperarousal and avoidance or numbness. I reviewed the psychobiological evidences in 3 main categories of symptoms and the biological treatment after a brief review of the epidemiology, psychosocial etiology and diagnosis of PTSD. The memory disturbance of PTSD might be developed by the potentiation of the memory pathway mediated by norepinephrine. PTSD induces HPA axis abnormality, it might also develop hippocampal dysfunction, which might contribute to the memory disturbance. The kindling effect develops desensitization, which might develop reexperiencing of the traumatic events and hyperarousal state. Chronic aroused state of locus ceruleus with resultant chronic maladaptive state of norepinephrine system, might develop hyperarousal state. Social avoidance and physical numbing state in PTSD might be caused by serotnin or opiate system. Stress induced analgesia might be developed by opiate reliesed against the acute stress. The biologic research results would help the selective treatment of PTSD.

• The Korean Journal of Pain
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• v.12 no.1
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• pp.21-26
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• 1999

Background: Preoperative blocking of surgical nociceptive inputs may prevent sensitization of central nervous system (CNS) and reduce postoperative pain. The stress responses to surgical trauma consist of increase in catabolic hormones and decrease in anabolic hormones. We studied whether preoperative low dose epidural bupivacaine and morphine could affect postoperative pain, changes plasma cortisol, and serum glucose. Methods: Thirty patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups. General anesthesia was induced in all patients and after that, epidural blocks were done except the control group (n=10) patients. Preoperative block group (n=10) received 0.5% bupivacaine 50 mg and morphine 2 mg epidurally as a bolus before operation and followed by 0.1% bupivacaine $5\;mghr^{-1}$ and morphine $0.2\;mghr^{-1}$ for 10 hours. Postoperative block group (n=10) received the same doses of bupivacaine and morphine under the same method postoperatively. Postoperative pain relief was provided with i.v. fentanyl through Patient-Controlled-Analgesia Pump. Postoperative pain by visual analogue scores (VAS), analgesic requirement (first requirement time, total amounts used), side effects, plasma cortisol level and serum glucose level were compared. Results: Until postoperative 6 hrs, VAS of control group was higher than those of the epidural groups. No difference was observed in VAS between the two epidural groups. First analgesics requirement time and total amounts of used analgesics were not different between the two epidural groups, but first analgesic requirement time of preoperative block group was significantly prolonged compared with control group. Plasma cortisol and serum glucose levels were not different among groups. Conclusions: Low dose preoperative epidural bupivacaine and morphine could not reduce postoperative pain, plasma cortisol level and serum glucose level compared with postoperative block group.

• The Korean Journal of Pain
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• v.11 no.2
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• pp.235-240
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• 1998

Background: Preoperative blocking of surgical nociceptive inputs may prevent sensitization of CNS and reduce postoperative pain. The stress responses to surgical trauma consist of increase in catabolic hormones and decrease in anabolic hormones. We studied whether preoperative intravenous morphine could affect postoperative pain and change plasma cortisol and serum glucose levels. Methods: Thirty eight patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups. Control group (n=11) did not received intravenous morphine, preoperative group (n=13) received intravenous morphine (0.1 mg/kg as a bolus 10 min before operation and followed by 1.5 mg/hr for 10 hours), postoperative group (n=14) received the same doses and method of intravenous morphine of preoperative group postoperatively. Postoperative pain relief was provided with i.v. fentanyl through Patient-Controlled-Analgesia Pump. Postoperative visual analogue scores (VAS), analgesic requirement (first request time, total amounts used), side effects, plasma cortisol and serum glucose levels were compared. Results: VAS were different between control group and the other two goups, but were not different between preoperative and postoperative group. Total amounts of used fentanyl were not different among groups, but first request time were significantly delayed in the preoperative group compared with the other two groups ($66.2{\pm}33.9$ vs $39.0{\pm}15.4$ and $45.0{\pm}14.9$ min respectively, p<0.05). Plasma cortisol and serum glucose levels were not different among groups. Conclusions: Above dosage of preoperative and postoperative morphine has analgesic effect, but could not block surgical stress induced plasma cortisol and serum glucose increase.

• The Korean Journal of Pain
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• v.6 no.2
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• pp.231-236
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• 1993

Clonidine, a centrally-acting antihypertensive agent known to reduce central sympathetic outflow and modulate presynaptic transmitter's release, has shown to suppress central noradrenergic hyperactivity induced by immobilization stress in animals, by decreasing the MAC of halothane and the dose of narcotics required to prevent reflex cardiovascular response to noxious stimuli, and to have potent analgesic properties in humans. These characteristics suggest that clonidine might be a useful adjunct to the anesthetic management of patients with preexisting hypertension. Accordingly, we determined the clinical efficacy and safety on analgesia, sedation and hemodynamic stability in the perioperative period. Thirty patients(ASA physical status II-III) with a history of arterial hypertension, scheduled for elective orthopedic surgery were randomly assigned to two groups. We applied CPA-clonidine patch($6.9\;mg/cm^2$, 0.2 mg delivered daily) or placebo patch to each groups, 48 hours prior to induction of anesthesia. Antihypertensive medication was continued until the morning of the scheduled surgery. All patients received premedication of atropine and lorazepam, and induced anesthesia with thiopental and succinylcholine, and maintained with enflurane and 50% nitrous oxide, while sustaining the BP and pulse rate at acceptable range. For the relief of pain postoperatively, diclofenac and fentanyl were administered intramuscularly on demand. The results were as follows: 1) The change of hemodynamic responses in clonidine group was less compared to the placebo group. 2) Intraoperative anesthetic requirement for enflurane in clonidine group were significantly lower than placebo group. 3) Postoperative analgetic requirement in clonidine group were significantly lower than placebo group. In clonidine group, 5 cases out of 15 cases were required no analgetics, and the incidence of administration of additional fentanyl was decreased to 5 cases, comparing with 10 cases in placebo group.

• Biomolecules & Therapeutics
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• v.13 no.1
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• pp.13-19
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• 2005

The study was undertaken to determine the antagonism of the AP1700 on the development of nalbuphine-induced tolerance and physical dependence. AP1700 is an oriental drug preparationcomposed of 5 natural products and is known to have antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of nalbuphine-induced physical dependence but does not the tolerance. Mitogen-activated protein kinase, which include extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) play critical roles in cell growth and survival and drug abuse. The level of pCREB was elevated in the hippocampus by the chronic treatment with nalbuphine, however, the elevation of pCREB was not inhibited by the AP1700 co-treatment. Interestingly, the level of pERK was decreased in the co-treatment with nalbuphine and AP1700 on the cortex and striatum. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or AP1700 on the cortex, hippocampus and striatum in the rat brain. These results suggest that the AP1700 could be used to ameliorate the nalbuphine withdrawal symptoms.

• Medical Lasers
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• v.8 no.2
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• pp.50-58
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• 2019

Background and Objectives Low-level light therapy (LLLT) is an application of low-power light for various purposes such as promoting tissue repair, reducing inflammation, causing analgesia, etc. A previous study suggested the effect of light emitting diode (LED) light with the wavelength of 740 nm for promoting wound healing of corneal epithelial cells. This current study aimed to confirm the effect of LLLT for managing inflammation of a dry eye disease (DED) mouse model. Materials and Methods A total of 50C57BL/6 female mice were randomly grouped into 5 groups to compare the effect of LLLT:1) Control group, 2) Only LLLT group, 3) Dry eye group, 4) LLLT in dry eye group, and 5) Early treatment group. DED was induced with 4 daily injections of scopolamine hydrobromide and desiccation stress for 17 days, and LLLT at 740 nm was conducted once every 3 days. To analyze the effect of LLLT on the DED mouse model, tear volume, corneal surface irregularities, and fluorescence in stained cores were measured, and the level of inflammation was assessed with immunohistochemistry. Results The DED mouse model showed significant deterioration in the overall eye condition. After LLLT, the amount of tear volume was increased, and corneal surface irregularities were restored. Also, the number of neutrophils and the level of inflammatory cytokines significantly decreased as well. Conclusion This study showed that LLLT at 740 nm was effective in controlling the corneal conditions and the degree of inflammation in DED. Such findings may suggest therapeutic effects of LLLT at 740 nm on DED.