Oral Administration Of Morphine Research Articles

Pharmacokinetics and thermal anti-nociceptive effects of oral morphine in horses.

Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.

Effects of oral morphine on experimentally evoked itch and pain: a randomized, double-blind, placebo-controlled trial.

Pain and itch share similar neuronal networks; hence, it is difficult to explain why opioids can relieve painbut provoke itching. The present human volunteer study aimed to investigate the similarities and differences in responses to experimentally provoked pain and itching to explore the underlying fundamental mechanisms. Twenty-four healthy volunteers were enrolled in this single-center, randomized, double-blind, placebo-controlled, parallel-group trial. Three volar forearms and two mandibular areas were marked, and participants randomly received morphine (20 mg) or identical placebo tablets. Heat, cold, and pressure pain thresholds, and vasomotor responses were assessed at baseline and after oral morphine administration. Itch provocations were induced by intradermal application of 1 % histamine or a topical cowhage (non-histaminergic itch) to a marked area of theskin. The participants were subsequently asked to rate their itching and pain intensities. The assessments were repeated for all marked areas. Morphine caused analgesia, as assessed by the significant modulation of cold and pressure pain thresholds (p<0.05). There were no significant differences in histaminergic or non-histaminergic itch or pain intensity between the morphine and placebo groups. Superficial blood perfusion (vasomotor response) following histamine provocation wassignificantly increased by morphine (p<0.05) in both areas. No correlation was found between the provoked itch intensity and analgesic efficacy in any area or group. Oral administration of morphine caused analgesia without modulating itch intensities but increased neurogenic inflammation in response to histamine, suggesting that different opioid mechanisms in histaminergic and non-histaminergic neurons evoke neurogenic inflammation.

Oral morphine induces spinal 5-hydroxytryptamine (5-HT) release using an opioid receptor-independent mechanism.

Morphine induces spinal 5-hydroxytryptamine (5-HT) release, but the role and mechanism of the spinal 5-HT release induced by morphine are not well understood. The purpose of this study was to define the role and mechanism of spinal 5-HT release induced by oral morphine. We also examined whether persistent pain affected the spinal 5-HT release induced by oral morphine. Spinal 5-HT release was measured using microdialysis of lumbar cerebrospinal fluid (CSF). Two opioids, morphine and oxycodone, were orally administered and 5-HT release was measured in awake rats. Naloxone and β-funaltrexamine (β-FNA) were used to determine whether the effect of morphine on 5-HT release was mediated by opioid receptor activation. To study persistent pain, a formalin test was used. At 45 min after oral morphine administration, the formalin test was started and spinal 5-HT release was measured. Oral morphine, but not oral oxycodone, increased 5-HT release at the spinal cord to approximately 4000% of the baseline value. This effect of morphine was not antagonized by either naloxone or β-FNA at a dose that antagonized the antinociceptive effect of morphine. Formalin-induced persistent pain itself had no effect on spinal 5-HT release but enhanced the oral morphine-induced spinal 5-HT release. Oral morphine-induced spinal 5-HT release was not mediated by opioid receptor activation. Spinal 5-HT induced by oral morphine did not play a major role in the antinociceptive effect of morphine in the hot plate test. Persistent pain increased oral morphine-induced spinal 5-HT release.

Concentrations, pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites following oral administration to horses.

The metabolism and pharmacokinetics of intravenous (i.v.) morphine in the horse have been described; however, administration of therapeutic doses has also been associated with neuroexcitation and adverse gastrointestinal effects. In this study, we hypothesized that oral administration would lead to comparable concentrations of morphine and its presumed active metabolite, morphine 6-glucuronide (M6G) without the adverse effects associated with i.v. administration. Eight horses were administered a single i.v. dose of 0.2mg/kg morphine and oral doses of 0.2, 0.6, and 0.8mg/kg of morphine in a four-way balanced crossover design, with a 2-week washout period between doses. Concentrations of morphine and metabolites were determined, and pharmacokinetic parameters determined. Physiologic and behavioral outcomes including the number of steps taken, changes in heart rate, and gastrointestinal borborygmi were assessed. Oral administration of morphine resulted in higher concentrations of morphine metabolites, including M6G (Cmax : 11.6-37.8ng/mL (0.6mg/kg); 15.8-42.6ng/mL (0.8mg/kg)), compared with i.v. Bioavailability was 36.5%, 27.6% and 28.0% for 0.2, 0.6 and 0.8mg/kg, respectively. Behavioral and physiologic changes were noted in all groups but were less prominent with oral compared with i.v. administration. Results of the current study are encouraging for further study, specifically anti-nociceptive effects of morphine following oral administration.

Nurses’ Knowledge and Attitudes Regarding Administration of Oral Morphine to Adult Cancer Patients in Medical Wards, Kenyatta National Hospital, Kenya

Nurses’ Knowledge and Attitudes Regarding Administration of Oral Morphine to Adult Cancer Patients in Medical Wards, Kenyatta National Hospital, Kenya

The effect of endurance exercise and methadone on μ-opioid receptor gene expression in morphine-dependent rats following withdrawal syndrome

Opiate dependence (e.g., morphine) is one of the most important problems affecting human health. Morphine reduces the irritability of neurons in the pain pathway by attaching to some such opioid receptors such as μ receptor (MOR). Exercise can improve destructions due to opiate dependence in many of the body organs including nerve systems. Thus, the aim of this study was to investigate the effect of endurance exercise training (8 weeks of moderate exercise) and methadone on μ-opioid receptor gene (OPRM1) expression in morphine-dependent rats following withdrawal syndrome. 48 male Wistar rats (9 weeks; weight: 295 ± 20 g) were kept as four animals per cage. The animals were selected and divided randomly into six subgroups of eight individuals: control (C), healthy exercise (TN), control addicts (CTM), addicts treated with methadone (MM), addicts treated with exercise (TM), and addicts treated with methadone plus exercise (TMM). In the present study, oral administration of morphine was used to induce dependence. Interventional therapy protocol also included a combination of methadone and a chronic aerobic exercise program. Changes in MOR gene expression levels were evaluated by RT-qPcR. Results showed a significant increase in MOR gene expression in the treatment with endurance training (TM) compared to the control group (C) (p < 0.05).Also, a significant increase in MOR gene expression was observed in the treatment group with methadone (MM) versus the normal group (C) (p < 0.05). It seems that physical activity, especially running on treadmill (endurance exercise) in animal model, can be considered as a non-medication and complementary therapy at various stages of dependence and addiction processes. However, further studies are needed especially in human sample.

Integrated Model to Describe Morphine Pharmacokinetics in Humans.

The pharmacokinetics (PK) of morphine has been extensively investigated. Though different publications have focused on the various aspects of morphine PK, none have quantitatively interpreted morphine PK across different publications. The objective of this research is to summarize the current understanding of morphine PK in humans quantitatively. In this research, a parent-metabolite compartmental PK modeling approach was used to summarize the current understanding of morphine PK in humans. Plasma concentration-time profiles and cumulative urine recovery time profiles of morphine, morphine-3-glucuronide, and morphine-6-glucuronide were digitized from the previous publications to develop the parent-metabolite PK model. The parent-metabolite PK model successfully described the plasma concentration-time profiles and cumulative urine recovery of morphine as well as its two major metabolites, morphine-3-glucuronide and morphine-6-glucuronide, after intravenous and oral administration of morphine. This research separated out the first-pass effect on morphine metabolism after oral administration. By integrating these results with two mass balance studies of morphine, a clear picture of morphine absorption and disposition is given. Though the results are mainly based on data collected from healthy volunteers or patients whose disease is not expected to impact morphine PK, the parent-metabolite model sets a framework to further evaluate morphine PK in special populations, such as pediatrics and patients with renal impairment.

Effects of Oral Morphine on Dyspnea in Patients with Cancer: Response Rate, Predictive Factors, and Clinically Meaningful Change (CJLSG1101).

Although the efficacy of parenteral morphine for alleviating dyspnea has been previously demonstrated in several studies, little is known regarding the efficacy of oral morphine for dyspnea among patients with cancer, including its response rate and predictive factors of effectiveness. Therefore, the aim of this study was to clarify the effectiveness of oral morphine on dyspnea in patients with cancer and elucidate the predictive factors of its effectiveness. In this multicenter prospective observational study, we investigated the change in dyspnea intensity in patients with cancer before and after the administration of oral morphine by using a visual analog scale (VAS). We also administered a self-assessment questionnaire to determine whether the patients believed oral morphine was effective. Eighty patients were enrolled in the study, and 71 of these patients were eligible. The least square mean of the VAS scores for dyspnea intensity was 53.5 at baseline, which decreased significantly to 44.7, 40.8, and 35.0 at 30, 60, and 120 minutes after morphine administration, respectively. Fifty-four patients (76.1%) reported that oral morphine was effective on the self-assessment questionnaire. Among the background factors, a high score for "sense of discomfort" on the Cancer Dyspnea Scale (CDS) and a smoking history of fewer pack-years were associated with greater effectiveness. Oral morphine was effective and feasible for treating cancer-related dyspnea. A higher score for "sense of discomfort" on the CDS and a smaller cumulative amount of smoking may be predictive factors of the effectiveness of oral morphine. This study demonstrated that oral morphine was effective in alleviating cancer-related dyspnea due to multiple factors including primary lung lesions, airway narrowing, and pleural effusion. Approximately 76% of patients reported that oral morphine was effective. A higher score for "sense of discomfort" on the Cancer Dyspnea Scale and a lower cumulative amount of smoking may be predictive factors for the effectiveness of oral morphine. Interestingly, respiratory rates in patients who reported the morphine to be effective decreased significantly after oral morphine administration, unlike the respiratory rates in "morphine-ineffective" patients.

Conditional and marginal relative risk parameters for a class of recursive regression graph models

In linear regression modelling, the distortion of effects after marginalizing over variables of the conditioning set has been widely studied in several contexts. For Gaussian variables, the relationship between marginal and partial regression coefficients is well established and the issue is often addressed as a result of W. G. Cochran. Possible generalizations beyond the linear Gaussian case have been developed, nevertheless the case of discrete variables is still challenging, in particular in medical and social science settings. A multivariate regression framework is proposed for binary data with regression coefficients given by the logarithm of relative risks, and a multivariate Relative Risk formula is derived to define the relationship between marginal and conditional relative risks. The method is illustrated through the analysis of the morphine data in order to assess the effect of preoperative oral morphine administration on the postoperative pain relief.

Morphine-Induced Constipation Develops With Increased Aquaporin-3 Expression in the Colon via Increased Serotonin Secretion.

Aquaporin-3 (AQP3) is a water channel that is predominantly expressed in the colon, where it plays a critical role in the regulation of fecal water content. This study investigated the role of AQP3 in the colon in morphine-induced constipation. AQP3 expression levels in the colon were analyzed after oral morphine administration to rats. The degree of constipation was analyzed after the combined administration of HgCl(2) (AQP3 inhibitor) or fluoxetine (5-HT reuptake transporter [SERT] inhibitor) and morphine. The mechanism by which morphine increased AQP3 expression was examined in HT-29 cells. AQP3 expression levels in rat colon were increased during morphine-induced constipation. The combination of HgCl(2) and morphine improved morphine-induced constipation. Treatment with morphine in HT-29 cells did not change AQP3 expression. However, 5-HT treatment significantly increased the AQP3 expression level and the nuclear translocation of peroxisome proliferator-activated receptor gamma (PPARγ) 1 h after treatment. Pretreatment with fluoxetine significantly suppressed these increases. Fluoxetine pretreatment suppressed the development of morphine-induced constipation and the associated increase in AQP3 expression in the colon. The results suggest that morphine increases the AQP3 expression level in the colon, which promotes water absorption from the luminal side to the vascular side and causes constipation. This study also showed that morphine-induced 5-HT secreted from the colon was taken into cells by SERT and activated PPARγ, which subsequently increased AQP3 expression levels.

The effectiveness of subcutaneously implanted epidural ports for relief of severe pain in patients with advanced-stage gynecological cancer: a prospective study

We aimed to evaluate the effectiveness of subcutaneously implanted epidural ports (SIEP) in the management of patients with advanced-stage gynecologic cancer-related severe chronic pain who do not respond to intravenous tramadol infusion, transdermal fentanyl, and oral morphine administration or who cannot tolerate the unacceptable and unmanageable side effects of these drugs. In this prospectively designed study, SIEP to permit the administration of morphine were implanted for relief of severe chronic pain in 21 cases with stage IV gynecological cancer (ovarian [n=6], endometrium [n=3], cervix [n=10], vaginal [n=1], and vulvar [n=1]). In order to define the level of pain, visual analogue scale (VAS) and patient satisfaction score (PSS) were used before and on the 5th, 15th, and 30th days after epidural port application. The mean overall survival period of the cases undergoing epidural port application was 80 days (range: 31-560). In terms of pain parameters, values at the end of the 5th, 15th and 30th days (VAS2, VAS3 and VAS4) were significantly lower than the value before morphine application via SIEP (VAS1) (p<0.01). PSSs at the 5th, 15th and 30th days were significantly higher than the PSS before port implantation (p<0.05). Pain management was started with 2 mg morphine with a maximum of 4 mg morphine administered into the epidural space per day. No clinically detected infectious condition or morphine-related side effects that required treatment occurred during the follow-up. Morphine administration via SIEP provided excellent pain relief without creating side effects, increased patient quality of life, and contributed to the patient's ability to enjoy life.

Variability in UDP-glucuronosyltransferase genes and morphine metabolism

The objective of the present study was to determine whether genetic variability in UDP-glucuronosyltransferase (UGT) genes, together with clinical factors, contribute to variability in morphine glucuronide (M6G and M3G) to morphine serum concentration ratios in patients with advanced cancer receiving chronic morphine therapy. A total of 41 polymorphisms and predicted haplotypes in the UGT2B7, UGT1A1, and UGT1A8 genes were analyzed in 759 patients who were recruited from the European Pharmacogenetic Opioid Study and received chronic morphine therapy by the oral route (n=635) or parenterally (n=124). The administration groups were analyzed separately by multiple linear regression analyses. Two haplotypes in UGT1A1/UGT1A8 were weak predictors of reduced M6G/morphine and M3G/morphine serum ratios after oral administration (false discovery rate-corrected P-values<0.1). No effect of genotype was seen in the parenteral group. Of the clinical variables (age, sex, BMI, renal function, Karnofsky performance status, and presence of liver metastases), renal function was the major contributor to variation in serum concentration ratios. Concomitant administration of paracetamol predicted significantly higher morphine metabolic ratios after oral administration of morphine (false discovery rate-corrected P-values<2.1E-12). The regression models explained about 35% of the total variability in the data. Genetic variation in the UGT genes together with clinical factors influence morphine metabolic ratios in patients with advanced cancer disease and who are scheduled with oral morphine. This information may be included in future research that develop and test new classification systems for opioid treatment in patients with advanced cancer.

Influence of Plasma-protein Binding on Analgesic Effect of Methadone in Rats with Spontaneous Withdrawal

The effect of spontaneous withdrawal on alpha 1-acid glycoprotein (AAG) levels and methadone protein binding has been studied in the rat. Animals were made physically dependent on morphine by providing morphine HCl in drinking water for three weeks. The natural opiate withdrawal was induced in rats by substituting the morphine solution with drinking water. The severity of the abstinence syndrome was assessed at various time intervals. After 12 h of withdrawal, the animals showing abstinence signs and low morphine levels were injected with intravenous methadone (0.35 mg kg-1) and the analgesic effect was measured by the tail-flick method and compared with animals receiving water. The oral administration of morphine produced an increase in AAG levels from 0.64 +/- 0.05 g L-1 in control animals to 1.47 +/- 0.92 g L-1 in experimental animals at the point of withdrawal and 1.21 +/- 0.09 g L-1 24 h after withdrawal. The percentage of methadone unbound was significantly lower in morphine-treated than in control animals. A significant correlation between AAG levels and percentage of methadone bound was observed. A parallel analgesic effect after intravenous methadone, as measured by AUC in the tail-flick test, was less in abstinence animals than in control (287.6 +/- 24.8 compared with 401.0 +/- 37.06s min). We suggest that in the withdrawal syndrome an adjustment of methadone dose may be necessary because of changes in protein binding.

Pharmacokinetic and pharmacodynamic study of morphine and morphine 6‐glucuronide after oral and intravenous administration of morphine in children with cancer

The aim of this study was to characterize the pharmacokinetics and pharmacodynamics of morphine and morphine 6-glucuronide (M6G) in children with cancer. Serum concentrations of morphine and M6G in children who received single oral or short term continuous intravenous morphine were determined by HPLC and ELISA assays, respectively. The serum C(max) of morphine and M6G after i.v. morphine administration was 560.5 and 309.0 nM and the T(max) was 61 and 65 min, respectively. The elimination half-life was 140.0 and 328.7 min, respectively. After oral administration of morphine, the serum C(max) of morphine and M6G was 408.34 and 256.3 nM and the T(max) was 40.0 and 60 min, respectively. The half-life was 131.0 and 325.8 min, respectively. The side effects were: drowsiness (100%), nausea and/or vomiting (57%), pruritus (28%) and urinary retention (14%). There were no reports of respiratory complications. This study showed that pharmacokinetics factors of morphine and M6G in children were significantly different from adults. Therefore the required dose for children should be different from that of adults and should be based on studies performed on children rather than on studies on adults. Some adverse effects, particularly nausea and pruritus, may be commoner than is usually thought, while others, particularly respiratory problems did not occur.

Kollidon ® SR colloidal particles as vehicles for oral morphine delivery in pain treatment

Due to the great importance of new therapeutic routes for morphine in pain treatment, several investigations are under development. In this way, the design of a liquid system for the oral administration of morphine would be of great help, especially in patients with difficulties in swallowing (children and elderly people). The systems studied in this work are kollidon ® SR microparticles, a biodegradable polymer classically used as excipient in the design of solid dosage forms, as vehicles for morphine. A detailed investigation of the capabilities of the polymer particles to load this drug at their surface is described. Electrophoretic mobility and optical absorbance determinations were used with this aim. The main factors determining the drug incorporation, after incubation of the microparticles in the morphine solutions, were the adsorption time, the type of electrolyte and its concentration, and the drug concentration. The optimum loading conditions were used to perform morphine release evaluations, finding that the release profiles were biphasic since the drug adsorbed was slowly released during 24 h after an initial burst release phase.

Intravenous Morphine Can Avoid Distressing Constipation Associated With Oral Morphine: A Retrospective Analysis of Our Experience in 11 Patients in the Palliative Care In-Patient Unit

Morphine is the preferred strong opioid analgesic. Most of the adverse effects, such as daytime drowsiness, dizziness, mental clouding, and effects on cognitive and psychomotor function or nausea and vomiting, usually resolve with time. The main continuing adverse effect of morphine is constipation, and prophylactic use of laxative is almost always required. We are presenting retrospective data of 11 patients admitted in our palliative care unit over the past 5 months for new (not yet received any opioid analgesic in any form) and severe cancer pain management. It was found that none of the patients was having constipation with intravenous morphine. This finding can be explained on the basis of differences in pharmacologic profiles, in affinity to opioid receptor, and a higher exposure of opioid-binding receptor in the GI tract after oral administration of morphine compared with intravenous morphine. This explanation was further affirmed as constipation and need for laxative was reported by 7 of the 11 patients when they were given the equi-analgesic oral doses of morphine. Thus, the route of administration seems to be responsible for the above finding; hence, further evaluation with prospective observation and data collection is being planned to look for external validity in a larger population catered by our palliative care unit.

Morphine does no promote esophageal carcinogenesis in rats exposed to diethylnitrosamine

The high incidence of esophageal cancer in the north of Iran has been associated to the consumption of opium and exposure to nitrosamines. Diethylnitrosamine has an established potential of producing experimental cancer in the esophagus and liver. To evaluate by histopathology the effect of oral administration of morphine and diethylnitrosamine during 23 weeks on the hepatic and esophageal carcinogenesis on 176 rats. We divided the rats into the following groups: Morph: morphine; Den: diethylnitrosamine; Den+morph: Den and morphine in the same solution; Den/morph: Den and morphine in different solutions and days. Morphine did not promote neoplasias. The highest neoplastic incidents were found: a) in the esophagus, Den in relation to Den/morph and Den+morph (71.1%, 55.8%, and 50.0%); b) in the liver, Den and Den/morph in relation to Den+morph (73.8%, 81.4%, and 40.9%); c) higher incident of hepatic neoplasia than esophageal in Den/morph (81.4% and 55.8%). Different doses of diethylnitrosamine were ingested among the groups Den, Den/morph, and Den+morph, respectively 2.9, 2.8, and 2.3 mg/kg/day. These results show that the morphine did not promote esophageal carcinogenesis and may have stimulated the hepatic metabolism of the first pass of the carcinogen.

The Cochrane Library and sickle cell disease: an overview of reviews

AbstractBackgroundSickle cell disease is a genetically inherited red blood cell disorder which features pain as a predominant manifestation.ObjectivesTo review the evidence within Cochrane systematic reviews on the management of pain associated with vaso‐occlusive crises and priapism secondary to sickle cell disease in paediatric populations.MethodsThe Cochrane Library of Systematic Reviews was searched for all reviews that addressed interventions to relieve pain associated with sickle cell disease. Reviews that primarily addressed the reduction of sickle cell crises were excluded. Data were extracted from included reviews.ResultsThree reviews were included. One review examined pharmacological interventions to relieve pain associated with vaso‐occlusive pain crises. One trial in children reported a significant reduction in VAS scores associated with ketorolac administration versus pethidine, but another trial performed in adults showed no significant reduction in VAS scores when ketorolac was compared to placebo. Two trials found that parenterally delivered corticosteroids reduced the length of analgesic therapy compared to placebo, and another trial found that there was no difference in the pain scores of children when morphine was delivered either parenterally or orally. Two trials reported on long‐term psychological interventions to manage pain. One found that coping skills training in children resulted in a reduction in the tendency to report pain, while the other trial found that cognitive behavioural therapy in adolescents and adults resulted in a decrease in the emotional component of pain but not the sensory component. One review addressed the treatment of stuttering priapism in boys and men using stilboestrol, but included an insufficient number of patients to draw a conclusion.Authors' ConclusionsPharmacological interventions to treat vaso‐occlusive pain crises show mixed results in the use of ketorolac and no difference between parenteral versus oral administration of morphine. Psychological interventions for vaso‐occlusive crises demonstrated benefit in improving some components of pain. Evidence regarding treatment of priapism was weak. Further studies should employ multi‐centre trials and begin to address generalisability concerns by more focus in Africa, where the majority of patients with sickle cell disease reside. Copyright © 2008 The Cochrane Collaboration. Published by John Wiley &amp; Sons, Ltd. The Cochrane Collaboration

Effect of parental morphine addiction on hippocampal long-term potentiation in rats offspring

Attention to addiction of women alone for fetus and infant's health has caused the possible role of father's status was less considered, while some developmental impairments including decrease of liter size, weight loss, congenital deficiencies, behavioral disorders, and learning and memory impairments in offspring with addicted father have been reported. In this study the effects of addiction of one or both parents to morphine on male and female offspring hippocampal long-term potentiation (LTP), were assessed.One hundred twenty female and 48 male rats (4–5 months, 250–270g) were used. Forty females and 16 males were addicted by oral administration of morphine (32mg/kg twice daily) for 5 days before mating. Then each two males with five females were housed (coupled) per cage as five groups for coupling: (A) addicted females+5% dextrose males (add.F); (B) addicted males+5% dextrose females (add.M); (C) addicted females+addicted males (add.MF); (D) 5% dextrose females+intact males (dex.F); (E) 5% dextrose males+intact females (dex.M). In puberty offspring LTP was induced in hippocampal dentate gyrus by stimulation of perforant path (pp). Changes of population spikes (PS) amplitude and LTP slope at 0, 5, 30, 60 and 120min were evaluated. Slope of LTP at 30, 60 and 120min, and amplitude of PS at 60 and 120min in add.F and add.M offspring were significantly lower than dextrose groups (P<0.01). LTP slope and PS amplitude of male and female offspring did not different between add.F and add.M groups. Our results suggest that both parental and paternal addiction to morphine may cause memory deficiency through reduction of LTP in hippocampus.

A pilot project of single nurse administration of oral morphine on a trauma ward

Summary Pain and its treatment is an important aspect of orthopaedic nursing. Delays in the administration of analgesia can be due to a variety of factors. Possible factors are discussed briefly and the delays due to controlled drug regulations are examined in more detail. Controlled drug legislation is also discussed. A small change in the administration of oral morphine was piloted on a trauma ward and resulted in a significant reduction in delays in its administration and evaluated positively by researchers from a local university. The change is currently being extended to other surgical and medical wards in the Royal Bolton Hospital.