Naloxone Group Research Articles

Effects of Atipamezole and Naloxone on Electroencephalographic Spectral Edge Frequency 95 in Dogs Sedated by Acupuncture at GV20 and Yintang Point

The purpose of this study was to evaluate the antagonism of acupuncture-induced sedation by electroencephalographic spectral edge frequency (SEF) 95 in 10 healthy intact male Miniature Schnauzer dogs (4.2-6.1kg; 2-3 years old) without neurological disorder. The GV20 and Yintang acupoints were administered for 20 min. While the dogs were conscious, SEF 95 baseline values were recorded at 2-min intervals for 4 min. Then acupuncture was administered at the GV20 and Yintang acupoints. During the acupuncture procedure, the SEF 95 values were recorded at 2-min intervals for 10 min. Subsequently, antagonist drugs, naloxone and atipamezole, were administered through the cephalic vein. The SEF 95 values were then measured again at 2-min intervals for 10 min. Those values were found to be significantly increased after administration of atipamezole in dogs sedated by acupuncture at the GV20 and Yintang acupoints (p<0.05). However, the SEF 95 values in the naloxone groups did not show any significant changes before and after administration of the antagonist. It was concluded that sedation induced by acupuncture at the GV20 and Yintang acupoints might be partially associated with the alpha(2)-adrenergic system.

Effects of low-dose naloxone on opioid therapy in pediatric patients: a retrospective case-control study

To develop novel therapies that prevent opioid tolerance in critically ill children we examined the effects of low-dose naloxone infusions on patients' needs for analgesia or sedation. Matched case-control study in a pediatric intensive care unit at a university children's hospital. We compared 14 pediatric ICU patients receiving low-dose naloxone and opioid infusions with 12 matched controls receiving opioid infusions. Opioid analgesia and sedative requirements were assessed as morphine- and midazolam-equivalent doses, respectively. No differences were observed between groups in opioid doses at baseline or during naloxone, but in the postnaloxone period opioid doses tended to be lower in the naloxone group. Compared to baseline the naloxone group required more opioids during naloxone but fewer opioids after naloxone. Total sedative doses were comparable at baseline in both groups, with no differences in the postnaloxone period. The naloxone group required less sedation after naloxone but sedation doses were unchanged in controls. The two groups did not differ in pain scores, sedation scores, or opioid side effects. Naloxone did not reduce the need for opioid during the infusion period but tended to reduce opioid requirements in the postnaloxone period without additional need for sedation. Randomized clinical trials may examine the effects of low-dose naloxone on opioid tolerance and side effects in pediatric ICU patients requiring prolonged opioid analgesia.

Naloxone and epinephrine are equally effective for cardiopulmonary resuscitation in a rat asphyxia model

It is not known whether naloxone is as efficacious as epinephrine during cardiopulmonary resuscitation (CPR). The aim of the study was to compare the effects of naloxone and epinephrine on the outcomes of CPR following asphyxial cardiac arrest in rats. Cardiac arrest was induced with asphyxia by clamping the tracheal tubes. Twenty-four Sprague-Dawley rats were randomized prospectively into a saline group (treated with normal saline, 1 ml intravenously, n = 8), an epinephrine group (treated with epinephrine, 0.04 mg/kg intravenously, n = 8) or a naloxone group (treated with naloxone, 1 mg/kg intravenously, n = 8) in a blind fashion during resuscitation after asphyxial cardiac arrest. After 5 min of untreated cardiac arrest, conventional manual CPR was started and each drug was administered at the same time. The rates of restoration of spontaneous circulation (ROSC) were one of eight (12.5%), seven of eight (87.5%) and seven of eight (87.5%) in the saline, epinephrine and naloxone groups, respectively. The rates of ROSC in the epinephrine and naloxone groups were equal and significantly greater than that in the saline group (P = 0.01 and P = 0.01, respectively). The administration of naloxone or epinephrine alone may increase the resuscitation rate, and both drugs are equally effective for CPR in a rat asphyxia model. However, the mechanism by which naloxone produces its efficacy during CPR remains unclear and further experimentation will be necessary.

Does naloxone alone increase resuscitation rate during cardiopulmonary resuscitation in a rat asphyxia model?

Cardiac arrest was induced with asphyxia to identify if naloxone alone increases resuscitation rate during cardiopulmonary resuscitation in a rat asphyxia model. The animals were randomized into either a saline group (Sal-gro, treated with normal saline 1 ml iv, n = 8), a low-dose naloxone group (treated with naloxone 0.5 mg/kg iv, n = 8), or a high-dose naloxone group (HN-gro, treated with naloxone 1 mg/kg iv, n = 8) in a blinded fashion during resuscitation. At the end of 10 minutes of asphyxia, cardiopulmonary resuscitation was started, and each drug was administered at the same time. The rate of restoration of spontaneous circulation was seen in 1 of 8, 3 of 8, and 7 of 8 animals in the Sal-gro, LN-gro, and HN-gro, respectively. The rate of restoration of spontaneous circulation in HN-gro was significantly higher than that in Sal-gro ( P < .05). Naloxone (1 mg/kg) alone can increase resuscitation rate following asphyxial cardiac arrest in rats.

Moderate hypercapnia-induced anesthetic effects and endogenous opioids

The purpose of this report is to explore the mechanisms of hypercapnia-induced antinociception. We carried out three experiments, the first to confirm whether moderate hypercapnia induces anesthetic effects, the second to determine whether naloxone reverses the anesthetic effects, and the third to evaluate whether β-endorphin is related to the anesthetic effects. In a pre-test, we determined the optimal CO 2 concentration in a chamber which would cause moderate hypercapnia in rats. Eighteen rats were divided into control, hypercapnia, and hypercapnia plus naloxone groups in experiment 1. The naloxone group rats were injected with naloxone (10 mg/kg) intraperitoneally before gas inhalation. After 60 min gas inhalation, 10% formalin was injected into the left rear paw of all rats, and nociceptive behaviors were observed for 1 h. In experiment 2, 11 rats were divided into control and hypercapnia groups. The brain was removed and fixed under pentobarbital anesthesia. Sections were immunostained for c-Fos and β-endorphin (ACTH) with the ABC method. All neurons double-labeled for c-Fos and β-endorphin (ACTH) in the arcuate nucleus were counted by blinded investigators. Moderate hypercapnia (PaCO 2 83 ± 7 mmHg) reduced nociceptive behavior in the formalin test and naloxone pre-treatment attenuated this phenomenon. However, β-endorphin-producing neurons were not activated by CO 2 inhalation. Endogenous opioids are related to moderate, hypercapnia-induced anesthetic effects, but, β-endorphin-producing neurons in the hypothalamus were not activated by the CO 2 inhalation stress.

Neonatal treatment with naloxone increases the population of Sertoli cells and sperm production in adult rats

Endogenous opioid peptides play an important role in the ontogenesis of the functional and morphological parameters of the seminiferous epithelium. The aim of this study was to evaluate the effects of neonatal manipulations with naloxone, an opioid antagonist, on the population of Sertoli cells and on sperm production in adult rats. Rats were assigned to receive 8 mug per gram of body weight twice a day with interval of 8 h of naloxone and they were compared to a control group receiving saline. Naloxone groups presented the following findings when compared to the control group: increased body weight from the 2nd to the 27th day; a smaller seminiferous epithelium height, smaller seminiferous tubule diameter, increased number of Sertoli cells and daily sperm production per testis, increased daily sperm production per gram per testis and increased total length of the seminiferous tubule of the treated groups. According to our study, the neonatal treatment with naloxone during the critical period of testis development was able to change the proliferative dynamics of Sertoli cells by an intra and/or extra testicular blockage of opioid receptors, confirming the direct relation between the number of Sertoli cells and the number of spermatozoids.

Effects of Naloxone on Stress-Induced Analgesia After Hemorrhagic Shock

To investigate whether endogenous opioids might be involved in the mechanisms that underlie hemorrhagic shock-induced analgesia, formalin tests were performed after hemorrhage and reinfusion in naloxone pretreated and untreated rats. Twenty-four adult male Sprague-Dawley rats were divided into control (n = 6), saline (n = 6), naloxone 10 mg/kg (n = 6), and naloxone 100 mg/kg (n = 6) groups. The mean blood pressure (mBP) was kept at 50 to 60 mm Hg for 30 minutes by draining arterial blood in the saline group and the naloxone groups. After 15 minutes of returning mBP to normal levels by reinfusion of the drained shed blood, 10% formalin (3.7% formaldehyde solution, 0.1 mL) was injected into the left rear paw. Nociceptive behaviors were observed for 1 hour after the formalin injection. Nociceptive behaviors of the posthemorrhagic shock groups were significantly lower than those of the control group. No significant difference was seen in nociceptive behaviors among the saline and naloxone groups. Naloxone did not reverse the hemorrhagic shock-induced analgesia, which suggests that endogenous opioids might not be a major factor that governs stress-induced analgesia (SIA) after hemorrhagic shock.

Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms

A study was conducted to determine whether changes in expected pain levels, desire for pain relief, or anxiety contribute to an increase in placebo analgesia over time as well as to determine whether placebo analgesic effects of IBS patients are related to endogenous opioid mechanisms. Twenty-six women with IBS were exposed to rectal stimulation (35 or 55 mmHg for 30 s) and tested under natural history (NH), rectal placebo (RP) and rectal lidocaine (RL) conditions. During all conditions, 16 patients were given saline intravenously (to test for a placebo effect) and 10 patients were given naloxone intravenously (to test naloxone antagonism of the placebo effect) on a double blind basis. Patients rated expected pain level, desire for pain relief and anxiety at 2 and 22 min after the onset of NH, RP, and RL conditions and they rated actual pain intensity at 5-min intervals for 40 min. There was a large and significant placebo effect ( P<0.001) that increased over time. Ratings of expected pain levels, desire for pain relief and anxiety decreased over time and contributed to more variance in placebo and lidocaine responses during the last half of the session. These changes suggest that a reduction in negative emotions may be central to placebo effects. There was no significant difference between psychological mediators (desire, expectation, anxiety) or the placebo effect in the saline and naloxone groups, indicating that neither the psychological mediators nor the placebo analgesic effect were associated with endogenous opioids in this clinically related paradigm.

The Role of Endogenous Opioids in Mediating Pain Reduction by Orally Administered Glucose Among Newborns

It has been demonstrated clearly that sweet-tasting solutions given before a painful intervention can reduce pain among newborns. There is no fully accepted explanation for this effect, but activation of endogenous opioids has been suggested as a possible mechanism. The aim of this study was to obtain deeper knowledge of the underlying mechanism by investigating whether administration of an opioid antagonist would reduce the effect of orally administered glucose at heel stick among term newborns. A randomized, placebo-controlled, double-blind trial with a validated, neonatal, pain-rating scale. The trial included 30 term newborns undergoing heel stick, who were assigned randomly to 1 of 2 groups, ie, group I, with naloxone hydrochloride (opioid antagonist) 0.01 mg/kg administered intravenously before oral administration of 1 mL of 30% glucose, or group II, with a corresponding amount of placebo (saline solution) administered intravenously before oral administration of glucose. Pain-related behavior during blood sampling was measured with the Premature Infants Pain Profile. Crying time and heart rate were also recorded. The 2 groups did not differ significantly in Premature Infant Pain Profile scores during heel stick. The median crying time during the first 3 minutes was 14 seconds (range: 0-174 seconds) for the naloxone group and 105 seconds (range: 0-175 seconds) for the placebo group. There was no significant difference in heart rate between the 2 groups. Administration of an opioid antagonist did not decrease the analgesic effect of orally administered glucose given before blood sampling.

Effects of Naloxone on Morphine Analgesia and Spinal c-fos Expression in Rat Formalin Test

Background: This study was performed to evaluate the dose-related effects of naloxone on morphine analgesia in the rat formalin test, and observe the correlation of pain behavior and spinal c-fos expression induced by a formalin injection. Methods: Fifty rats were divided into five groups; control, morphine (morphine pre-treated, intra-peritoneal injection of 0.1 mg of morphine 5 min prior to formalin injection), and three naloxone groups, which were divided according to the administered dose-ratio of naloxone to morphine 20 : 1 (5), 10 : 1 (10), and 1 : 1 (100) representing the low-, medium-, and high-dose naloxone groups, respectively, were injected intra-peritoneally 16 min after a formalin. A fifty ul of 5% formalin was injected into the right hind paw. All rats were observed for their pain behavior according to the number of flinches during phases 1 (2 3, 5 6 min) and 2 (1 min per every 5 min from 10 to 61 min). The spinal c-fos expression was quantitatively analyzed at 1 and 2 hours after the formalin injection using a real-time PCR. Results: The morphine pre-treated (morphine and three naloxone) groups during phase 1, and the morphine, low- and medium-dose naloxone groups during phase 2, showed significantly less flinches compared to those of the control (P

Naloxone lowers cerebrospinal fluid levels of excitatory amino acids after thoracoabdominal aortic surgery

Although naloxone has been used to prevent ischemic spinal cord injury (SCI), its effect on excitatory amino acids (EAAs) has not been understood. We investigated the clinical significance of naloxone by measuring EAAs in the cerebrospinal fluid (CSF) in patients undergoing thoracoabdominal aortic surgery. Twenty-seven patients (15 men and 12 women; mean age, 66 +/- 12 years) undergoing prosthetic replacement of the thoracoabdominal aorta (n = 19) or the descending thoracic aorta (n = 8) from April 1997 to June 2003 under distal perfusion and mild hypothermia were enrolled in this cohort study with historical controls. Their etiology was 7 dissections and 20 nondissections. In 16 patients (naloxone group), intravenous infusion of naloxone (1 microg/kg/h) was continued until the patients became alert. In the remaining 11 patients (control group) naloxone was not given. CSF drainage was used in all patients. CSF levels of EAAs, glutamate, aspartate, and glycine were measured at 6 points in time until 72 hours postoperatively, using a high-performance liquid chromatography method. In 5 patients with SCI (2 patients in control group, 3 in naloxone group), CSF levels of glutamate and glycine continued to increase even at 72 hours postoperatively, and were significantly more elevated than those in patients without SCI ( P < .0001, glutamate; P = .0006, glycine). Postoperative maximum levels of CSF glutamate and glycine were also significantly higher in patients with postoperative SCI than in patients without SCI (glutamate: 215.3% +/- 158.6% vs 32.9% +/- 37.3% increase from baseline, P < .0001; glycine: 309.1% +/- 218.2% vs 89.2% +/- 103.1% increase from baseline, P = .0036). CSF levels of glutamate and aspartate in naloxone group were significantly lower than those in control group ( P = .0161, glutamate; P < .0001, aspartate). Postoperative maximum level of CSF aspartate was also significantly lower in the naloxone group than in the control group (8.3% +/- 75.5% vs 119.7% +/- 120.6% increase from baseline, P = .0077). In multivariate logistic regression analysis, postoperative maximum CSF glutamate >100% from baseline ( P < .001) and postoperative maximum level of CSF glycine ( P = .005)were identified as the independent risk factors for SCI. Both SCI ( P < .001) and postoperative maximum level of CSF glycine ( P = .005) were the independent predictors for postoperative maximum level of CSF glutamate >100% from baseline. CSF levels of EAAs are elevated in patients with SCI. CSF glutamate is the strongest independent predictor of SCI. Naloxone is effective in lowering CSF levels of EAAs.

Effect of naloxone on food competition aggression in food-restricted high and low aggression pigeons (Columba livia).

We determined the effect of the opiate receptor antagonist naloxone on aggression, emotion, feeder control, and eating behavior in high and low aggression female pigeons maintained at 80% of their normal weight and exposed to food competition interactions. Pigeons were divided into pairs by previously ranked high aggression (total time spent in offensive aggression exceeding 60 s/5 min; N=6 pairs) and low aggression females (time spent in offensive aggression less than 10 s/5 min; N=6 pairs). A pigeon in each pair received an s.c. dose of naloxone (1 mg kg(-1) ml saline(-1)) and the other animal received the vehicle. Trials (10 min) were performed 30 min after the naloxone/vehicle administration. The naloxone group of high aggression pigeons showed lower scores of total time spent in offensive aggression (control: 98.6 +/- 12.0; naloxone: 46.8 +/- 6.6 s; P<0.05) and higher scores of time spent in emotional responses (control: 3.5 +/- 0.6; naloxone: 10.8 +/- 2.4 s; P<0.05) than controls. The other behaviors scored, feeder control and eating behavior, were not affected in this group. The naloxone group of low aggression pigeons, however, showed higher scores of offensive aggression than their controls (5.3 +/- 1.3; naloxone: 28.7 +/- 8.0 s; P<0.05). The present results suggest that opiate receptor mechanisms are implicated in offensive aggression responses in high and low aggression pigeons. However, as reported for brain 5-hydroxytryptamine manipulation and GABA-A-benzodiazepine receptor manipulation, the effect of the opiate receptor antagonist on food competition aggression in pigeons was related to their pretreatment level of aggression.

Addition of ultralow dose naloxone to postoperative morphine PCA: unchanged analgesia and opioid requirement but decreased incidence of opioid side effects

Ultralow doses of naloxone (0.001–0.1 μg/kg) produce analgesia in animal models. However, no clinical study has evaluated the combination of ultralow dose naloxone and morphine using patient-controlled analgesia (PCA). This randomized, double blind controlled study sought to determine if the combination of ultralow dose naloxone and morphine in PCA solutions affects opioid requirements, analgesia, and side effects. Two-hundred and sixty-five patients (18–65 years old) undergoing operations were randomized to receive PCA morphine 1 mg/ml ( n=129) or PCA morphine 1 mg/ml plus naloxone 0.6 μg/ml ( n=136). We evaluated the numbers of supplemental rescue doses, the cumulative dose of each PCA solution, pain intensity, pain relief, and opioid side effects during the first 24 h after surgery. We found that opioid requirements did not differ significantly between groups. The morphine+naloxone group on average required 0.07 mg more morphine (95% CI −1.1 to 1.3) during the 24 h than the morphine group. Pain intensity levels were also similar in both groups. The morphine+naloxone group had 0.06 units lower (95% CI −0.5 to 0.4) pain intensity levels than the morphine group. The morphine+naloxone group had a lower incidence of nausea and pruritus than the morphine group ( P=0.01 for both symptoms). However, the incidence of vomiting, time to tolerate fluids, sedation, and urinary retention were similar between groups (all P values >0.1). The combination of ultralow dose naloxone and morphine in PCA does not affect analgesia or opioid requirements, but it decreases the incidence of nausea and pruritus.

Naloxone for shock.

There is pre-clinical evidence, involving several animal species, suggesting that opioid peptides play a role in the physiopathology of shock (endotoxic, hypovolemic, cardiogenic, spinal, anaphylactic). Many case reports have suggested that naloxone (an opiate antagonist) might be an effective treatment for shock in humans, but others have not supported such a point of view. This controversy led us to undertake a meta-analysis of the available evidence on the efficacy of naloxone as a treatment measure of shock in humans. To evaluate the effectiveness and safety of naloxone in human shock and to estimate the methodological quality of the clinical trials. Computerized bibliographic search up to December 2002, review of references of all papers found on the subject and contact with primary investigators of eligible studies. Randomized controlled trials evaluating naloxone in human shock, regardless of the patient's age (adult, child or neonate). Three independent reviewers extracted data on study design, intervention, outcome and methodological quality. Three independent readers reviewed 80 human publications and selected six clinical trials. Overall agreement on study selection was perfect (concordance: 100%). This meta-analysis includes six studies involving 126 patients with septic, cardiogenic, hemorrhagic or spinal shock. Naloxone therapy was associated with statistically significant hemodynamic improvement (odds ratio 0.24; 95% confidence interval [95%CI] 0.09-0.68). The mean arterial pressure was significantly higher in the naloxone groups than in the placebo groups (weighted mean difference: +9.33 mmHg; 95%CI 7.07-11.59). No heterogeneity was found for this outcome. The death rate was lower in the naloxone group (odds ratio 0.59; 95%CI 0.21-1.67) but this was consistent with the play of chance. A significant heterogeneity for the latter outcome was detected (p<0.05). Naloxone improves blood pressure, especially mean arterial blood pressure. However, the clinical usefulness of naloxone to treat shock remains to be determined, and additional randomized controlled trials are needed to assess its usefulness.

The Effectiveness of Combined Naloxone/Lofexidine in Opiate Detoxification: Results from a Double-blind Randomized and Placebo-controlled Trial

The efficacy of lofexidine/naloxone was compared with lofexidine/placebo in a double-blind, randomized, placebo-controlled trial in 89 opiate-dependent patients. There were no significant differences between the two groups in the proportion of patients completing detoxification or in the length of stay. Patients in the active naloxone group demonstrated gradual reductions in levels of withdrawal and craving over the detoxification period. At completion of detoxification, patients who received naloxone maintained a level of withdrawal consistently lower than that in the placebo group; however, naloxone did not substantially accelerate the resolution of the withdrawal syndrome. Implications for future research are discussed.

Spinal amino acid release and repeated withdrawal in spinal morphine tolerant rats.

1. We used spinal microdialysis in awake rats to investigate whether the repeated withdrawal with naloxone during continuous spinal infusion of morphine would lead to a progressively greater spinal glutamate release and a more pronounced intrathecal tolerance. 2. Rats received lumbar intrathecal (IT) infusion of morphine (IT-M: 20 nmol microl(-1) h(-1)) or saline (IT-S: 1 microl h(-1)) continuously for 3 days. Both groups were further subdivided to receive intraperitoneal (i.p.) injection of naloxone (IP-N: 0.6 mg kg(-1)) or saline (IP-S: 3 ml kg(-1)) every 24 h after the beginning of IT infusion. Daily thermal escape latencies, withdrawal signs, the resting basal release of spinal amino acids before IP injection and the release immediately after the injection (evoked) were measured. 3. Rats receiving IT morphine showed a maximum increase in thermal escape latency on day 1, after which this value declined, with the fastest decline observed in IT morphine + IP naloxone group. On day 1, no significant difference was observed among groups in the resting basal release of amino acids. Rats in IT morphine + i.p. naloxone group displayed a progressive increase in this value. The release was not significantly altered in other groups. 4. For the IT-M + IP-N group, basal resting dialysate concentrations of Glu, Asp and Tau rose steadily over the 3-day infusion interval. No change in basal resting release was noted for any other treatment. 5. Evoked release (after i.p. naloxone) in IT-M animals displayed a progressive increase over the three repeated exposures. Evoked release did not change significantly in other treatment groups. 6. The degree of precipitated withdrawal significantly correlated with the increase in glutamate acutely evoked by i.p. injection. 7. The present results show that periodic transient withdrawal of spinal opiate agonist activity leads to a progressive increase in glutamate outflow and withdrawal signs, in a manner consistent with an enhanced development of spinal tolerance.

Morphine withdrawal-induced abnormalities in the VTA: confocal laser scanning microscopy.

Morphine withdrawal is characterized by functional alterations at the level of the ventrotegmental area. We investigated the effects of chronic morphine administration and withdrawal on the morphological properties of immuno-labelled tyrosine hydroxylase-positive neurons of the rat ventrotegmental area with a confocal laser scanning microscope. Morphological evaluation revealed a reduction in the area and perimeter of tyrosine hydroxylase-positive somata in morphine-withdrawn rats. Conversely, the number of cells per field was found to have increased in the naloxone group. Collectively, the present results indicate that withdrawal from a chronic morphine treatment, and not chronic morphine per se, modifies cellular morphology of tyrosine hydroxylase-positive, presumably dopamine-containing, neurons of the rat VTA. This is consistent with the idea that withdrawal from morphine alters functioning of the mesolimbic dopamine system and provides a direct morphological correlate for the functional abnormalities typical of morphine withdrawal.

Inhibition of oxytocin release during repeated milking in unfamiliar surroundings: the importance of opioids and adrenal cortex sensitivity.

The aim of this study was to test if the opioid antagonist naloxone has a beneficial effect on normalization of oxytocin (OT) release during repeated milking of cows in unfamiliar surroundings. One control milking without naloxone treatment in all cows was performed in the familiar parlour. For four successive evening milkings, cows were transported to, and milked in, the operating theatre of the research station without (control group) or with naloxone administration (1 mg/kg BW) (naloxone group) before milking. After cessation of spontaneous milk flow, but not before 3 min of milking, vaginal stimulation was applied for 2 min. After milk flow ceased again, 10 IU of OT was injected intravenously to remove the remaining milk including residual milk. Milk flow was recorded continuously and blood samples were collected via a jugular vein cannula at 1-min intervals from 1 min before the start of milking until i.v. injection of OT. The inhibition of milk ejection and its normalization during repeated milking in unfamiliar surroundings was not influenced by naloxone treatment. Concentrations of cortisol and beta-endorphin during control milking and all relocations were similar in the naloxone and control groups, although their concentrations were higher after relocations than in the control. Therefore, a role of endogenous opioids in the inhibition of milk ejection in unfamiliar surroundings could not be demonstrated. In addition, the effect of exogenous ACTH1-24 (8 IU, i.v.) on the release of cortisol related to the response of cows milked in unfamiliar surroundings was studied. Cows with totally inhibited milk ejection in response to vaginal stimulation during milking after first relocation had numerically, but not significantly lower cortisol levels (8.8+/-3.4 ng/ml; AUC/min) in response to ACTH than did cows with at least partial milk ejection (38.7+/-12.9 ng/ml). Thus animals with a higher adrenal response to ACTH seemed to have less severe inhibition of milk ejection.

The combination of low dose of naloxone and morphine in PCA does not decrease opioid requirements in the postoperative period

The continuous infusion of low doses of naloxone has been reported to decrease postoperative opioid requirements and opioid side effects. However, there is no study that evaluates the effectiveness of the combination of a low dose of naloxone and morphine using patient-controlled analgesia (PCA). This prospective, randomized double-blind controlled study sought to determine if the combination of a low dose of naloxone and morphine in a PCA solution decreases postoperative opioid requirements and pain intensity. One hundred sixty-six patients (18–65 years old) undergoing operations of less than 3 h duration with an American Society of Anesthesiologist physical status I or II were randomized to receive PCA morphine 1 mg/cc plus normal saline or PCA morphine 1 mg/cc plus naloxone 6 μg/cc. Initial PCA settings were 0.5 cc per demand with a lockout time of 10 min. The numbers of 2.5 cc supplemental rescue doses and the cumulative dose of each solution were recorded in the first 24 h after the surgical procedure. Pain intensity and opioid side effects were evaluated every 10 min in the post-anesthesia care unit and every 4 h afterwards. Patient satisfaction was assessed at the end of the 24 h of observation. The morphine+naloxone group had more treatment failures ( P=0.0001), higher opioid requirements ( P=0.0097), greater pain intensity ( P=0.04), less pain relief ( P=0.004), and less satisfaction ( P=0.01) than the morphine group. The incidence of side effects was similar in both groups ( P=0.3). Contrary to previous reports, adding low doses of naloxone to a morphine PCA solution increases opioid requirements and pain.

Real-Life Stress and Opioid-Mediated Analgesia in Novice Parachute Jumpers

Abstract It was investigated whether a stress-induced analgesia could be demonstrated in human subjects (N = 24) performing a first-time parachute jump. Sensitivity for electrical stimulation and pressure pain was measured at several moments before and after the jump. The opioid antagonist naloxone or saline placebo was administered immediately after the jump to examine possible opioid-mediated effects. After the jump, the placebo group showed a lower pain sensitivity than the naloxone group, with the latter returning to pretest levels, consistent with an opioid-mediated analgesia. Although analgesic effects appear to have been initiated prior to the jump, plasma β-endorphin showed a sudden large increase immediately after the jump. This increase correlated with reports of anxiety and loss of control during the jump, and was associated with reduced pain sensitivity. Despite several limitations, this study suggests that the real-life stress of a parachute jump may attenuate pain through endogenous opioid release.