OBJECTIVETo observe the effects of remifentanil combined with naloxone on human sperm motility in vitro and to investigate its possible mechanism.

METHODSTwenty normal semen samples were collected, each divided into 13 aliquots, one as the control and the others treated in vitro with different concentrations of remifentanil or remifentanil + naloxone for 35 min. The percentage of progressive mobile sperm was assessed by computer-assisted sperm analysis at 5, 10, 15, 20 and 35 min.

RESULTSCompared with the control group, remifentanil at 0.1, 1, 10 and 100 microg/L significantly decreased sperm motility at 5 and 10 min in a dose-dependent manner, with no significant difference at 15 and 30 min; sperm motility showed no significant difference on 5 -35 min exposure to naloxone at 0.004 -0.04 mg/L, nor on 5, 10, 15 and 20 min exposure at 0.4 -4 mg/L, but was significantly increased at 35 min. Compared with the corresponding concentrations of remifentanil alone, remifentanil + naloxone remarkably increased sperm motility at 0.1 + 0.004, 1 + 0.04, 10 + 0.4, and 100 + 4 mg/L at 5 and 10 min, with no obvious difference at 15 and 30 min.

CONCLUSIONThe onset and offset of the effect of remifentanil on sperm motility are rapid and its inhibitory effect can be antagonized by naloxone, which may be related with the micro-opioid receptor.

Adult ; Humans ; Male ; Naloxone ; administration & dosage ; pharmacology ; Piperidines ; administration & dosage ; pharmacology ; Sperm Motility ; drug effects ; Spermatozoa ; drug effects ; Young Adult

Opioids are the one of the most commonly used drugs to control cancer pain all over the world. But, we should not overlook the potential risk of opioid intoxication because they have well-known detrimental side effects. The opioid intoxication can be diagnosed thorough various clinical manifestations. The altered mental status, respiratory depression, and miosis is very representative clinical features although these symptoms don't always appear together. Unfortunately the opioid-toxidrome can be varied. A 42 years old man came to our emergency room after taking about 900 mg morphine sulfate per oral. He was nearly alert and his respiration was normal. Even though his symptoms didn't deteriorated clinically, serial arterial blood gas analysis showed increase in PaCO2. So we decided to use intravenous naloxone. Soon, he was fully awaked and his pupils size was increased. After a continuous infusion of intravenous naloxone for 2 hours, PaCO2 decreased to normal range and his pupil size also returned to normal after 12 hours. Though the levels of serum amylase and lipase increased slightly, his pancreas was normal according to the abdominal computed tomography. He had nausea, vomit, and whole body itching after naloxone continuous infusion, but conservatively treated. We stopped the continuos infusion after 1 day because his laboratory results and physical examinations showed normal. As this case shows, it is very important to prescribe naloxone initially. If you suspect opioid intoxication, we recommend the initial use of naloxone even though a patient has atypical clinical features. In addition, we suggest intranasal administration of naloxone as safe and effective alternative and it's necessary to consider nalmefene that has a longer duration for opioid intoxication.
Administration, Intranasal ; Amylases ; Analgesics, Opioid ; Blood Gas Analysis ; Emergencies ; Humans ; Lipase ; Miosis ; Morphine ; Naloxone ; Naltrexone ; Nausea ; Pancreas ; Physical Examination ; Porphyrins ; Pruritus ; Pupil ; Reference Values ; Respiration ; Respiratory Insufficiency

The present study was to evaluate effects of vitamin E on intravenous administration of lidocaine-induced antinociception. Experiments were carried out using male Sprague-Dawley rats. Orofacial formalin-induced nociceptive behavioral responses were used as the orofacial animal pain model. Subcutaneous injection of formalin produced significant nociceptive scratching behavior. Intraperitoneal injection of 5 and 10 mg/kg of lidocaine attenuated formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. Intraperitoneal injection of 1 g/kg of vitamin E also attenuated the formalin-induced nociceptive behavior in the 2nd phase, compared to the vehicle-treated group. However, low dose of vitamin E (0.5 g/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. The present study also investigated effects of intraperitoneal injection of both vitamin E and lidocaine on orofacial formalin-induced behavioral responses. Vehicle treatment affected neither formalin-induced behavioral responses nor lidocaine-induced antinociceptive effects. However, intraperitoneal injection of 0.5 g/kg of vitamin E enhanced the lidocaine-induced antinociceptive effects in the 2nd phase compared to the vehicle-treated group. Intraperitoneal injection of naloxone, an opioid receptor antagonist, did not affect antinociception produced by intraperitoneal injections of both vitamin E and lidocaine. These results suggest that treatment with vitamin E enhances the systemic treatment with lidocaine-induced antinociception and reduces side effects when systemically treated with lidocaine. Therefore, the combined treatment with vitamin E and lidocaine is a potential therapeutic for chronic orofacial pain.
Administration, Intravenous ; Animals ; Facial Pain ; Formaldehyde ; Humans ; Injections, Intraperitoneal ; Injections, Subcutaneous ; Lidocaine* ; Male ; Naloxone ; Rats* ; Rats, Sprague-Dawley ; Receptors, Opioid ; Vitamin E* ; Vitamins*

The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 microliter of 5% formalin solution was applied to the hindpaw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level.
Analgesics/*administration & dosage ; Analgesics, Opioid/*administration & dosage ; Animals ; Behavior, Animal/drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Formaldehyde/toxicity ; Injections, Spinal ; Male ; Morphine/*administration & dosage ; Naloxone/administration & dosage ; Narcotic Antagonists/administration & dosage ; Pain/chemically induced/therapy ; Pain Measurement/drug effects ; Phosphodiesterase Inhibitors/*administration & dosage ; Piperazines/*administration & dosage ; Purines/administration & dosage ; Rats ; Rats, Sprague-Dawley ; Sulfones/*administration & dosage ; Time Factors

BACKGROUNDS: Pain can occur following acute noxious stimuli and tissue damage. The duration of such pain may outlast the stimulus and its amplitude may be exaggerated (hyperalgesia). This response comes from a sensitization of the peripheral nociceptor. Traditional thought has associated the antinociceptive effects of opiates with the activation of opioid receptors located in the central nervous system. Recently, however, opiate receptors in the peripheral nervous system have led to the hypothesis that analgesic action might, in part, result from a reduction in the response of peripheral nerve fibers thought to be concerned with signaling pain. METHODS: Twenty units were recorded from the strands of the hypogastric nerve innervating the urinary bladder of the cat. Nerve activity and intravesical pressure were monitored before and after the onset of an acute inflammation induced by the intravesical instillation of 2% mustard oil. The responses of afferent units to chemical stimuli by intra-arterially injected bradykinin (10 microgram/0.2 ml., i.a.) and potassium chloride (0.3 M/0.2 ml, i.a.) were compared each time at control, after inflammation, and after administration of morphine (2.5 mg/kg) and naloxone (5 microgram/kg) respectively. RESULTS: Polymodal receptors in the urinary bladder showed excitatory response to algesic substances such as bradykinin, potassium chloride and the urinary bladder contracted simultaneously, both the responses of the nerve impulse and bladder contraction to bradykinin and potassium chloride increased significantly after bladder inflammation induced by 2% mustard oil and the sensitization of the sensory receptors attenuated by morphine and naloxone reversed the effect of morphine. CONCLUSIONS: These observations suggest that morphine might have a peripheral effect.
Action Potentials ; Administration, Intravesical ; Animals ; Bradykinin ; Cats ; Central Nervous System ; Inflammation ; Morphine* ; Mustard Plant ; Naloxone ; Nociceptors ; Peripheral Nerves ; Peripheral Nervous System ; Potassium Chloride ; Receptors, Opioid ; Sensory Receptor Cells* ; Urinary Bladder*

BACKGROUNDEarly studies showed that naloxone infusion decreases the incidence of morphine-related side effects from intravenous patient-controlled analgesia. This study aimed to determine whether naloxone preserved analgesia while minimizing side effects caused by intravenous tramadol administration.

METHODSEighty patients undergoing general anesthesia for cervical vertebrae surgery were randomly divided into four groups. All patients received 1 mg/kg tramadol 30 minutes before the end of surgery, followed by a continuous infusion with 0.3 mg x kg(-1) x h(-1) tramadol with no naloxone (group I, n = 20), 0.05 microg x kg(-1) x h(-1) naloxone (group II, n = 20), 0.1 microg x kg(-1) x h(-1) naloxone (group III, n = 20) and 0.2 microg x kg(-1) x h(-1) naloxone (group IV, n = 20). Visual analog scales (VAS) for pain during rest and cough, nausea five-point scale (NFPS) for nausea and vomiting, and ramsay sedation score (RSS) for sedation were assessed at 2, 6, 12, 24 and 48 hours postoperatively. Analgesia and side effects were evaluated by blinded observers.

RESULTSSeventy-eight patients were included in this study. The intravenous tramadol administration provided the satisfied analgesia. There was no significant difference in either resting or coughing VAS scores among naloxone groups and control group. Compared with control group, sedation was less in groups II, III, and IV at 6, 12, and 24 hours (P < 0.05); nausea was less in groups II, III and IV than group I at 2, 6, 12, 24 and 48 hours postoperatively (P < 0.05). The incidence of vomiting in the control group was 35% vs. 10% for the highest dose naloxone group (group IV) (P < 0.01).

CONCLUSIONA small-dose naloxone infusion could reduce tramadol induced side effects without reversing its analgesic effects.

Analgesia, Patient-Controlled ; methods ; Analgesics, Opioid ; administration & dosage ; adverse effects ; therapeutic use ; Anesthesia, General ; methods ; Cervical Vertebrae ; surgery ; Female ; Humans ; Infusions, Intravenous ; Male ; Middle Aged ; Naloxone ; administration & dosage ; adverse effects ; therapeutic use ; Narcotic Antagonists ; administration & dosage ; adverse effects ; therapeutic use ; Nausea ; chemically induced ; Tramadol ; administration & dosage ; adverse effects ; therapeutic use

OBJECTIVETo compare the analgesic effect and side effects of morphine for intravenous patient-controlled analgesia (PCA) with or without low-dose naloxone after abdominal surgery.

METHODSFifty-nine ASA I - II patients undergoing elective abdominal surgery were randomly divided into two groups: group morphine received postoperative PCA with 0.4 mg/ml morphine (a 1 mg bolus with a 5 min lockout), group naloxone received morphine 0.4 mg/ml with 6 microg/kg naloxone. Blood pressure, heart rate, respiratory rate, and pulse oxygen saturation were monitored. Visual analogue scale (VAS), nausea/vomiting, pruritus, sedation and consumption of morphine were recorded for 24 hours.

RESULTSVAS had no difference between group morphine and group naloxone, but group naloxone had significantly lower VAS for pain at rest or movement (beyond 4-8 h), and the incidence of nausea/vomiting significantly decreased in group naloxone (P < 0.05). No differences existed in pruritus, sedation, respiratory rate, and hemodynamic parameters between these two groups. The 24 hours postoperative morphine consumption was (36.6 +/- 13.5) mg in group naloxone and (43.7 +/- 14.6) mg in group morphine (P < 0.05).

CONCLUSIONFor morphine PCA, morphine with 6 microg/kg naloxone is effective in preventing some PCA morphinerelated side effects. Naloxone not only reduces postoperative morphine requirements but also improves the analgesic effect.

Abdomen ; surgery ; Adult ; Analgesia, Patient-Controlled ; methods ; Analgesics, Opioid ; administration & dosage ; adverse effects ; Female ; Humans ; Hysterectomy ; Male ; Middle Aged ; Morphine ; administration & dosage ; adverse effects ; Naloxone ; administration & dosage ; adverse effects ; Narcotic Antagonists ; administration & dosage ; adverse effects ; Pain Measurement ; drug effects ; Pain, Postoperative ; drug therapy ; prevention & control

OBJECTIVETo investigate the analgesic effect of interleukin-2 (IL-2) in mice with spared nerve injury (SNI).

METHODIL-2 was intraperitoneally injected in mice with induced SNI, and von Frey Filaments test and cold plate test were carried out to accesses the analgesic effects of IL-2 and the effect of naloxone in antagonizing the effects of IL-2.

RESULTSIL-2 produced analgesic effects against hyperalgesia and allodynia in mouse models of SNI, and the effect of IL-2 lasted for more than 24 h, showing a double-peak pattern in its action with the two peaks occurring at 30 and 105 min, respectively. The effect of IL-2 could be significantly antagonized by naloxone.

CONCLUSIONSIL-2 has long-lasting analgesic effects in mouse models of SNI model, showing a double-peak pattern of its action. The analgesic effect of IL-2 is probably mediated by opiate receptor.

Analgesics ; administration & dosage ; antagonists & inhibitors ; pharmacology ; therapeutic use ; Animals ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Humans ; Hyperalgesia ; complications ; drug therapy ; Interleukin-2 ; administration & dosage ; antagonists & inhibitors ; pharmacology ; therapeutic use ; Male ; Mice ; Mice, Inbred BALB C ; Naloxone ; pharmacology ; Trauma, Nervous System ; complications ; drug therapy

OBJECTIVETo investigate the effects of ephedrine combined with various doses of naloxone on neural plasticity in rats after cerebral ischemia/reperfusion injury to explore the possibility of synergistic effect about ephedrine combined with naloxone, promoting the optimum ratio of neural remodeling and its molecular mechanism.

METHODA total of 192 healthy adult Sprague-Dawley rats, 220-250 g, were used to establish models of left middle cerebral artery occlusion using the suture occlusion method. Were randomly divided into 8 groups: the rats were intraperitoneally injected with 1.5 mg x kg(-1) x d(-1) ephedrine (ephedrine group), with 0.1, 0.2, 0.3 mg x kg(-1) x d(-1) naloxone (low, moderate and high doses of naloxone groups) , with 1.5 mg x kg(-1) x d(-1) ephedrine + 0.1, 0.2, 0.3 mg x kg(-1) x d(-1) naloxone (ephedrine + low, moderate and high doses of naloxone groups), and with 0.5 mL saline (model group), respectively. At 1-4 weeks following cerebral ischemia, sensorimotor integration in rats was assessed using the beam walking test, brain-derived neurotrophic factor (BDNF) expression was detected in the hippocampal CA3 area using immunohistochemistry 1-4 weeks after surgery, immunofluorescence method of detecting ischemic hemisphere hippocampal expression, The number of nerve cells apoptosis was detected using TUNEL assay.

RESULTBWT, BDNF, TUNEL assay results showed three doses of naloxone group had no significant effect, the effects increased together with the quantitative ephedrine, and had the amount-effect relationship, in which ephedrine + high dose of naloxone group the recovery of movement was fastest, BDNF expression in the best and ischemic apoptosis in the hippocampus at least, ischemic injury to the minimum, speed up the process of neural remodeling.

CONCLUSIONThe ephedrine and ephedrine + naloxone groups were accelerated motor function recovery rate in rat after cerebral ischemia, and the promotion of neural remodeling is closely related to the expression of BDNF, inhibit apoptosis in ischemic area, and with the increase of naloxone amount of additives, its role more clearly, the mechanism may be related to the dose of naloxone can significantly inhibit the ischemic area of apoptosis in early cerebral ischemia, so had the positive synergy effect with ephedrine to speed up the formation of neural remodeling.

Animals ; Apoptosis ; drug effects ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Brain-Derived Neurotrophic Factor ; genetics ; metabolism ; Disease Models, Animal ; Ephedrine ; administration & dosage ; Female ; Hippocampus ; drug effects ; metabolism ; physiopathology ; Humans ; Male ; Naloxone ; administration & dosage ; Neuronal Plasticity ; drug effects ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Spinal gabapentin has been known to show the antinociceptive effect. Although several assumptions have been suggested, mechanisms of action of gabapentin have not been clearly established. The present study was undertaken to examine the action mechanisms of gabapentin at the spinal level. Male SD rats were prepared for intrathecal catheterization. The effect of gabapentin was assessed in the formalin test. After pretreatment with many classes of drugs, changes of effect of gabapentin were examined. General behaviors were also observed. Intrathecal gabapentin produced a suppression of the phase 2 flinching, but not phase 1 in the formalin test. The antinociceptive action of intrathecal gabapentin was reversed by intrathecal NMDA, AMPA, D-serine, CGS 15943, atropine, and naloxone. No antagonism was seen following administration of bicuculline, saclofen, prazosin, yohimbine, mecamylamine, L-leucine, dihydroergocristine, or thapsigargin. Taken together, intrathecal gabapentin attenuated only the facilitated state. At the spinal level, NMDA receptor, AMPA receptor, nonstrychnine site of NMDA receptor, adenosine receptor, muscarinic receptor, and opioid receptor may be involved in the antinociception of gabapentin, but GABA receptor, L-amino acid transporter, adrenergic receptor, nicotinic receptor, serotonin receptor, or calcium may not be involved.
Acetic Acids/administration & dosage ; Acetic Acids/metabolism ; Acetic Acids/pharmacology* ; Adrenergic Antagonists/metabolism ; Adrenergic alpha-Antagonists/metabolism ; Analgesics/administration & dosage ; Analgesics/metabolism ; Analgesics/pharmacology* ; Animals ; Atropine/metabolism ; Dihydroergocristine/metabolism ; Enzyme Inhibitors/metabolism ; Excitatory Amino Acid Agonists/metabolism ; GABA Antagonists/metabolism ; Injections, Spinal ; Leucine/metabolism ; Male ; Mecamylamine/metabolism ; Muscarinic Antagonists/metabolism ; N-Methylaspartate/metabolism ; Naloxone/metabolism ; Narcotic Antagonists/metabolism ; Nicotinic Antagonists/metabolism ; Pain Measurement ; Quinazolines/metabolism ; Rats ; Rats, Sprague-Dawley ; Serine/metabolism ; Spinal Cord/drug effects* ; Thapsigargin/metabolism ; Triazoles/metabolism ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism