BACKGROUND: Opioids can produce potent antinociceptive effects by interacting with local opioid receptors in inflamed peripheral tissue. However, reports on pain relief with intra-articular morphine after arthroscopic knee operations are conflicting. In this study we examined the analgesic effects of the intraarticular administration of morphine after knee surgery. METHODS: In a double-blind, randomized trial, we studied 26 patients who had received one of two injections at the end of surgery. The patients in group M(n=11) received 3 mg of morphine intraarticularly; those in group P(n=15), saline 20 ml intraarticularly as a placebo. RESULTS: Patients in the morphine group had significantly lower pain scores throughout the 24-h postoperative period compared with those in the placebo group(P<0.05). There was less requirement for supplementary analgesics in the morphine group. CONCLUSIONS: Low doses of intraarticular morphine can significantly reduce pain after knee surgery without any systemic side effect.
Analgesics ; Analgesics, Opioid ; Humans ; Knee* ; Morphine* ; Postoperative Period ; Receptors, Opioid

Opiate receptor agonists (especially dynorphin - a kappa receptor agonist) have found to increase in the injuried segment of spinal cord. It is known to cause spinal cord damage when injected intrathecally. Nalbuphine is a kappa opiate receptor agonist/partial mu antagonist, and fentanyl is selective mu receptor agonist. To determine the effect of nalbuphine and fentanyl on experimental spinal cord injuries of Spague-Dawley rats (N=125): 1) I determinded the MAC (or ED50) values of enflurane, fentanyl, nalbuphine-enflurane in 65% N2O; 2) produced spinal cord injury model by different epidural ballooning time in the control (enflurane) gmup ; 3) produced spinal cord injuries in the experimental (fentanyl, nalbuphine-enflurane) group. The results were as follows ; 1) The MAC value of enflurane was 1.16+/-0.05%, and the ED50 values of fentanyl were 26.8, 36.2, 39.7, 44.7 ug/kg after 15, 30, 45, 60 min of injection, respectively. Also the MAC values of enflurane with 20 mg/kg nalbuphine were 1.08, 0.99% after 60, 90 min of injection, respectively. 2) We produced the graded spinal cord injuries by different epidural ballooning time. 3) The total neurological scores of fentanyl experimental group were significantly higher than control group on the 10th, 14th, and 21st postinjury day.
Animals ; Dynorphins ; Enflurane ; Fentanyl* ; Nalbuphine* ; Rats ; Receptors, Opioid ; Receptors, Opioid, kappa ; Receptors, Opioid, mu ; Spinal Cord Injuries* ; Spinal Cord*

BACKGROUND: Previous studies have suggested synergistic analgesic drug interactions between NSAIDs and opioids in neuropathic and inflammatory pain models. The aim of this study was to investigate the analgesic drug interaction between intraperitoneal (IP) ketorolac and morphine in radiant thermal stimulation rat. METHODS: Initially, we assessed the withdrawal latency time of the hindpaw to radiant thermal stimulation every 15 min for 1 hour and every 30 min for next 1 hour after IP normal saline 5 ml (control group). The latency time was changed into percent maximal possible effect (%MPE). Next, IP dose response curves were established for the %MPE of morphine (0.3, 1, 3, 10 mg/kg) and ketorolac (3, 10, 30 mg/kg) to obtain the ED50 for each agent. And we confirmed that the IP morphine effect was induced by opioid receptor through IP morphine followed by IP naloxone. At last, we injected three doses of IP ketorolac (3, 10, 30 mg/kg) mixed with one dose of morphine (2 mg/kg) for fixed dose analysis. RESULTS: IP morphine delayed the paw withdrawal latency time dose dependently, but not ketorolac. ED50 of IP morphine was 2.1 mg/kg. And the IP morphine effect was reversed to control level by IP naloxone. IP ketorolac + morphine combination showed no further additional effects on paw withdrawal latency time over morphine only group. CONCLUSIONS: IP ketorolac did not produce antinociceptive effect during radiant thermal stimulation. There was neither additional nor synergistic analgesic interaction between IP morphine and ketorolac in thermal stimulation rat.
Analgesics, Opioid ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Drug Interactions ; Ketorolac* ; Morphine* ; Naloxone ; Rats* ; Receptors, Opioid

This study was designed to investigate the contribution of prostaglandins to the maintenance of inflammatory pain. Inflammation was induced by intraplantar (i.pl.) injection of carrageenan in right hindpaw in rats. Indomethacin (non-selective COX inhibitor) was administered i.pl. 1 h after the carrageenan injection, and paw withdrawal latency (PWL) responding to noxious heat was measured. β-endorphin (β-END) and μ-opioid receptor (MOR) expressed in the inflamed site were examined by using immunocytochemistry, ELISA and RT-PCR techniques. The results showed that indomethacin dose-dependently increased PWL to the levels that were above the baseline on the day 2 and 3, referred to as hypoalgesia. The hypoalgesia was abolished by a local injection of the non-selective opioid receptor inhibitor naloxone methiodide. The number of β-END-positive cells, the content of β-END and the expression of MOR mRNA in the inflammatory site of inflammation model rats were all significantly increased by indomethacin. These results reveal a novel mechanism of prostaglandins for the inhibition of inflammation-induced endogenous opioid activity. This study provides further evidence that inhibition of prostaglandins in inflamed site could be a promising therapy for inflammatory pain.
Analgesics, Opioid ; Animals ; Carrageenan ; Indomethacin ; Inflammation ; Naloxone ; Pain ; Prostaglandins ; Rats ; Receptors, Opioid ; beta-Endorphin

The study was to investigate the proliferation and apoptosis effect of nociceptin/orphanin FQ (OFQ) on 562 cells in vitro. Inhibition of K562 cells proliferation was measured by MTT assay. Morphological assessment of apoptosis was performed with Wright staining and transmission electron microscope. The apoptosis peak was measured by flow cytometry. DNA fragmentation was visualized by agarose gel electrophoresis. The results showed that OFQ time-dependently and no-dose-dependently inhibited the proliferation of K562 cells at concentrations of 10(-6) - 10(-13) mol/L. Discrete maximum of cytolytic activity was detected at concentrations of 10(-6) - 10(-7), 10(-9), 10(-12) mol/L. Compared with the control group K562 cells, the cells treated with OFQ at concentration of 10(-9) mol/L for 72 hours showed typical characteristics of apoptosis under transmission electron microscope. Apoptosis peak was found by FCM at concentration of 0, 10(-7), 10(-8), 10(-9) mol/L of OFQ for 72 hours, apoptosis rates were 0%, 22.8%, 23.8% and 26.5% respectively. DNA agarose gel electrophoresis revealed nuclear fragmentation (DNA ladder). It is concluded that OFQ can inhibit the proliferation of K562 cells and induce the apoptosis in K562 cells.
Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Humans ; K562 Cells ; Opioid Peptides ; pharmacology ; Receptors, Opioid ; agonists

To investigate the receptors mediating the regulation of norepinephrine (NE) release in human cerebral cortex slices, we examined the effects of opioid agonists for mu-, delta-, and kappa -receptors on the high potassium (15 mM) -evoked release of [3H]NE. [3H]NE release induced by high potassium was calcium-dependent and tetrodotoxin-sensitive. [D-Pen2, D-Pen5]enkephalin (DPDPE) and deltorphin II (Delt II) inhibited the stimulated release of norepinephrine in a dose-dependent manner. However, Tyr-D-Ala-Gly- (Me) Phe-Gly-ol and U69, 593 did not influence the NE release. Inhibitory effect of DPDPE and Delt-II was antagonized by naloxone, naltrindole, 7-benzylidenaltrexone and naltriben. These results suggest that both delta 1 and delta 2 receptors are involved in regulation of NE release in human cerebral cortex.
Analgesics, Opioid* ; Cerebral Cortex* ; Enkephalin, D-Penicillamine (2,5)- ; Humans* ; Naloxone ; Negotiating ; Norepinephrine ; Potassium ; Receptors, Opioid

Recent studies have shown that opiods can produce potent antinociceptive effects by interacting with opioid receptors in peripheral tissues. This study sougt to compare the effects of morphine with those of-bupivacaine administered intraarticularly upon pain after arthroscopic knee surgery. In a ramdomized manner, 60 healthy patients received either morphine(3 mg in 20 ml NaCl : n=20), bupivacaine(20 ml, 0.25% : n=20) intraarticularly at the completion of surgery, and others were not administered (n = 20) under general anesthesia after 1, 2, 4, 6, 12 and 24h of postoperative day, pain was assessed by a visual analogue pain scalps, time to first analgesic use were recorded. Pain scores were signicantly greater in the morphine group than two groups at 11. From 4th until the end of the study period, pain scores were significantly greater in the bupivaca.ne group than in the other two group. Anagesic requirements were significantly greater in the morphine group than two groups at 1h but were significantly greater in the bupivacaine group than in the other groups throughout the remainder of the study period. The results suggest that intraarticular morphine produces an analgesic effect of delayed onset but of remarkably long duration.
Anesthesia, General ; Bupivacaine* ; Humans ; Knee* ; Morphine* ; Receptors, Opioid ; Scalp

Although ample evidence has shown that acute stress impairs memory, the influences of acute stress on different phases of memory, such as acquisition, consolidation and retrieval, are different. Experimental data from both human and animals support that endogenous opioid system plays a role in stress, as endogenous opioid release is increased and opioid receptors are activated during stress experience. On the other hand, endogenous opioid system mediates learning and memory. The aim of the present study was to investigate the effect of acute forced swimming stress on recognition memory of C57 mice and the role of opioid receptors in this process by using a three-day pattern of new object recognition task. The results showed that 15-min acute forced swimming damaged the retrieval of recognition memory, but had no effect on acquisition and consolidation of recognition memory. No significant change of object recognition memory was found in mice that were given naloxone, an opioid receptor antagonist, by intraperitoneal injection. But intraperitoneal injection of naloxone before forced swimming stress could inhibit the impairment of recognition memory retrieval caused by forced swimming stress. The results of real-time PCR showed that acute forced swimming decreased the μ opioid receptor mRNA levels in whole brain and hippocampus, while the injection of naloxone before stress could reverse this change. These results suggest that acute stress may impair recognition memory retrieval via opioid receptors.
Animals ; Learning ; Memory ; Mice ; Naloxone ; Receptors, Opioid ; Swimming

The mechanisms underlying opiate tolerance and dependence are not fully understood. We used human neuroblastoma SH-SY5Y cells as a model system for studying effects of morphine tolerance and withdrawal on c-myc induction and cAMP levels. It has been reported that regulation of c-fos by acute and chronic morphine withdrawal is mediated through alterations in CREB transcription factor. In this study, we examined the effects of morphine tolerance on c-myc expression and cAMP concentrations. The activation of opiate receptors by an acute morphine administration resulted in an increase in c-myc mRNA and a decrease in cAMP concentrations in a dose-dependent manner (5, 10, 15, and 20 muM). On the other hand, the chronic treatment of morphine (10 muM for six days) did not induce the elevated expression of c-myc mRNA. The c-myc expression was slightly inhibited in comparison with that of the acute morphine response. However, cAMP concentrations were increased with regard to morphine withdrawal response. These results suggest that the alterations in c-myc expression might imply a significant opiate regulation relating to morphine tolerance. This observation differs from increased expression of c-fos via regulation of cAMP pathway.
Hand ; Humans* ; Morphine ; Neuroblastoma* ; Receptors, Opioid ; RNA, Messenger ; Transcription Factors

Neuraxial opioid administration is one of the most common methods of anesthesia and analgesia,while itching is the most troublesome adverse effect.The current treatments for neuraxial opioid-induced pruritus still have certain limitations.This article reviews the current treatments and basic scientific findings(including neurotransmitters,opioid receptors,and signaling pathways)of pruritus caused by neuraxial opioids.Based on our recent findings on N-methyl-D-aspartate(NMDA)receptors and pruritus caused by neuraxial opioids,we provide new ideas for the treatment of itching caused by neuraxial opioids.Since NMDA receptors may play a key role in neuraxial opioid-induced pruritus,NMDA receptor antagonists can have certain therapeutic advantages.
Analgesics, Opioid ; Humans ; Pruritus ; Receptors, N-Methyl-D-Aspartate