Glial contributions to visceral pain: implications for disease etiology and the female predominance of persistent pain.

In the central nervous system, bidirectional signaling between glial cells and neurons ('neuroimmune communication') facilitates the development of persistent pain. Spinal glia can contribute to heightened pain states by a prolonged release of neurokine signals that sensitize adjacent centrally projecting neurons. Although many persistent pain conditions are disproportionately common in females, whether specific neuroimmune mechanisms lead to this increased susceptibility remains unclear. This review summarizes the major known contributions of glia and neuroimmune interactions in pain, which has been determined principally in male rodents and in the context of somatic pain conditions. It is then postulated that studying neuroimmune interactions involved in pain attributed to visceral diseases common to females may offer a more suitable avenue for investigating unique mechanisms involved in female pain. Further, we discuss the potential for primed spinal glia and subsequent neurogenic inflammation as a contributing factor in the development of peripheral inflammation, therefore, representing a predisposing factor for females in developing a high percentage of such persistent pain conditions.

A bio-assay for effectors of osteoclast differentiation in serum from patients with bone disease.

UNLABELLED: Osteoclast differentiation and activity, and hence bone loss, depend on two opposing cytokines. Receptor activator of NF-(kappa)B ligand (RANKL) produced by osteoblasts and T-cells stimulates, while osteoprotegerin inhibits. Both of these cytokines are found in serum. Our aim was to develop a functional assay for any factors present in human serum that can affect osteoclast differentiation and to assess whether any such factors vary in diseases in which bone loss occurs. METHODS: Using a culture model of osteoclast differentiation in the presence of macrophage colony stimulating factor and soluble RANKL, we have measured the effects of different human sera on osteoclast differentiation. The production of a marker enzyme for the osteoclast, tartrate-resistant acid phosphatase (TRAP), was used to follow osteoclast differentiation. RESULTS: In general, human serum stimulates osteoclast differentiation as indicated by TRAP activity, but in patients with low bone density this stimulation was attenuated. Sera from 40 female subjects with low bone mineral density showed significantly lower TRAP cell differentiation activity than sera from the healthy female controls. CONCLUSION: We describe a functional bio-assay for factors in human serum which can affect osteoclast differentiation. This assay may have application in monitoring the effects of therapy in bone disease.

Adjustment for current weight and the relationship between birth weight and blood pressure in childhood.

OBJECTIVE: To determine the role of current weight in mediating the relationship between birth weight and blood pressure within the context of the 'fetal origins' hypothesis. DESIGN: Prospective cohort study of 2507 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia between 1989 and 1992. The study commenced at 16 weeks gestation with serial weight and blood pressure measurements recorded through early childhood. RESULTS: Inverse associations were found between birth weight and systolic blood pressure at ages 1, 3 and 6. The effect of birth weight on systolic blood pressure at age 6 reached statistical significance and was increased fourfold in magnitude to -2.3 mmHg [95% confidence interval = (-3.3 to -1.3), P < 0.01] after adjustment for current weight. The interaction term for birth weight and current weight was not statistically significant. Including intermediate weights did not produce a statistically significantly better model but did increase the magnitude of the estimated regression coefficient of birth weight on blood pressure, and only the birth weight and current weight terms were significant CONCLUSIONS: Adjustment for current weight serves to highlight the relationship between birth weight and blood pressure in childhood. Nevertheless, birth weight, rather than birth weight adjusted for current weight, is still the relevant predictor of later blood pressure within the context of the 'fetal origins' hypothesis.

Effects of intravascular volume expansion on the cardiovascular response to naloxone in a canine model of severe endotoxin shock.

The specific opiate receptor antagonist, naloxone, can produce haemodynamic improvement and increased survival in experimental shock. The efficacy of naloxone therapy in a canine model of endotoxin shock has been evaluated both with and without intravascular volume replacement. Animals were anaesthetized with alpha-chloralose and allowed to breathe spontaneously. A large bolus dose of endotoxin was followed by a continuous infusion and treatment was instituted one hour after the endotoxin bolus. In the absence of volume replacement, naloxone caused only limited and transient increases in mean arterial pressure (MAP) and left ventricular (LV) dp/dt max, with little effect on cardiac index (CI). Total peripheral resistance index (TPRI) tended to rise in both control and naloxone-treated dogs. In volume-replaced animals, naloxone produced substantial and sustained increases in the MAP and LV dp/dt max with an associated rise in the CI. TPRI rose initially in this series and then fell progressively. Further analysis of the improvements in the CI showed an increase in stroke index with a tendency for heart rate to fall. These findings suggest a myocardial action of naloxone in endotoxin shock, which is augmented by volume replacement. An initial, transient vasoconstrictor effect cannot, however, be excluded. Further work is required to determine the mechanism of the effects described.

A new canine model of endotoxin shock.

A new canine model of endotoxin shock has been developed in which spontaneous recovery of cardiovascular function is largely prevented, the haemodynamic effects of anaesthesia are minimized and intravascular volume replacement is given. This model has been evaluated using two groups of five adult mongrel dogs anaesthetized with alpha-chloralose and breathing spontaneously. Animals in one group were anaesthetized, instrumented and given Escherichia coli (E. coli) endotoxin intravenously, whilst those in the control group were subjected only to anaesthesia and instrumentation. E. coli endotoxin was given to dogs in the shock group as a bolus dose of 5 mg kg-1 followed by a continuous infusion at 2 mg kg-1 h-1. This produced immediate, severe, cardiovascular depression, with precipitous falls in mean arterial pressure (MAP), cardiac index (CI), stroke index (SI) and left ventricular (LV) dp/dt max. There were associated increases in systemic and pulmonary vascular resistances. Arterio-venous oxygen content difference (C(a-v)O2) increased after induction of shock, and animals developed a progressive metabolic acidosis. Increasing haemoconcentration occurred, as evidenced by a rising haematocrit (PCV). Hypovolaemia was reflected by a concurrent fall in pulmonary capillary wedge pressure (PCWP). One hour after induction of shock, intravascular volume replacement was given in the form of a colloidal gelatin solution, as a bolus dose of 10 ml kg-1, followed by a continuous infusion at 10 ml kg-1 h-1. Volume replacement reversed haemoconcentration, restored PCWP and produced some haemodynamic improvement, although in general, severe cardiovascular depression persisted throughout a three hour observation period. This severe endotoxin shock model has proved to be stable, reproducible and economical. It provides a useful preliminary test for new methods of treatment in hypodynamic endotoxin shock, as well as allowing investigation of acute metabolic and physiological changes.

Characterization of circulating pro-opiomelanocortin-related peptides in human septic shock.

The nature of circulating pro-opiomelanocortin (POMC)-related peptides was investigated in patients with a diagnosis of septic shock. Also, changes following administration of methylprednisolone were monitored using established chromatographic techniques and three radioimmunoassays directed towards the N-terminal, mid-portion and C-terminal regions of the precursor. Adrenocorticotrophin and beta-endorphin-like peptides were identified in the circulation. By 60 min after a pharmacological dose of methylprednisolone (30 mg/kg) concentrations of these peptides were reduced and continued to fall up to 180 min. beta-Lipotrophin and N-terminal POMC(1-76) were also detected by the beta-endorphin and gamma 3-MSH assays respectively. The concentrations of these peptides were noticeably reduced only after 180 min. The 31,000 Da MSH/ACTH/beta-endorphin (POMC) and the 22,000 Da MSH/ACTH precursors were also present in the circulation in septic shock and their concentrations increased following steroid treatment.

Effect of corticosteroids on brain growth in fetal sheep.

OBJECTIVE: To compare the effects of single and repeated courses of corticosteroids on brain growth in fetal sheep. METHODS: Pregnant sheep were given intramuscular betamethasone (0.5 mg/kg) at 104 days' gestation followed at 111, 118, and 124 days by equivalent volumes of sterile normal saline (n = 12) or betamethasone (n = 12). Controls received equivalent volumes of sterile normal saline at all four intervals (n = 12). Lambs were delivered at 125 (preterm) or 145 (term) days. After perfusion, we measured weights (grams) for whole brain, cerebrum, cerebellum, and brain stem, volumes (milliliters) for whole brain and cerebrum, and maximum cerebral anterior-posterior length, width, and depth (centimeters). RESULTS: In the single-injection group at preterm, there were no significant differences (P = .070) in whole-brain weight between the corticosteroid-treated animals (38.0 +/- 1.81 g) and controls (42.5 +/- 1.65 g). Cerebral length and depth were significantly reduced in the corticosteroid group (P < .05); other measures were not significantly different. At term, whole-brain weight was significantly lower (47.5 +/- 1.70 g; P = .022) compared with controls (53.4 +/- 1.73 g). All other measures were significantly reduced (P < .05) except cerebral and brain-stem weights and cerebral length. In the group that received repeated injections at preterm, whole-brain weight was significantly reduced (35.5 +/- 1.65 g; P = .005) compared with controls (42.5 +/- 1.65 g). All other measures were significantly reduced (P < .05) except cerebellar and brain-stem weights. At term, whole-brain weight was also significantly reduced (42.4 +/- 1.52 g; P = .001) compared with controls (53.4 +/- 1.73 g) as were all other measures (P < .05). CONCLUSION: Administration of single and repeated courses of corticosteroids to pregnant sheep retarded fetal brain growth.

Repeated prenatal corticosteroid administration delays astrocyte and capillary tight junction maturation in fetal sheep.

Glucocorticoids are powerful regulators of cell differentiation and maturation. Their synthetic counterparts, the corticosteroids, are used widely in obstetric practice to enhance fetal lung maturation in cases of threatened preterm birth. Here we examined the effects of repeated corticosteroid administration on astrocyte and capillary tight junction development in the fetal sheep brain, selecting the corpus callosum for analysis. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104, 111, 118 and 124 days gestation. Lambs were delivered at term, terminally anaesthetized and transcardially perfused. Transverse semi-thin sections of the corpus callosum were cut and immuno-stained with antibody against glial fibrillary acidic protein (GFAP). Ultra-thin sections were examined in the electron microscope. The percentage area of GFAP staining was reduced in the corticosteroid-treated group compared to control (5.2 vs. 8.7%, P<0.05). The expression of GFAP in peri-capillary and parenchymal astrocytes was also reduced compared to control (peri-capillary: 3.0 vs. 9.5 microm2; parenchymal: 14.6 vs. 29.4 microm2, P<0.05). Furthermore, capillary tight junction maturation was delayed compared to control. Immature 'type II' junctions were more common in the corticosteroid-treated group (63 vs. 22%, P<0.05), whereas more mature 'type III' junctions were less common (27 vs. 65%, P<0.05). Our data suggest that repeated corticosteroids delay both astrocyte and capillary tight junction maturation. The implications for clinical practice are as yet unknown.

Repeated prenatal corticosteroid administration delays myelination of the corpus callosum in fetal sheep.

Glucocorticoids regulate oligodendrocyte maturation and the myelin biosynthetic pathways. Synthetic glucocorticoids, the corticosteroids have been successfully used in clinical practice as a single course to enhance lung maturation and reduce mortality and morbidity in preterm infants with no long-term neurologic or cognitive side effects. However, a trend has arisen to use repeated courses despite an absence of safety data from clinical trials. We examined the effects of clinically appropriate, maternally administrated, repeated courses of corticosteroids on myelination of the corpus callosum using sheep as a large animal model. The corpus callosum is a major white matter tract that undergoes protracted myelination, underpins higher order cognitive processing and developmental damage to which is associated with, for example, cerebral palsy, mental retardation and attention deficit hyperactivity disorder. Pregnant ewes were given saline or betamethasone (0.5 mg/kg) at 104,111,118 and 124 days gestation, stages equivalent to the third trimester in humans. Lambs were delivered at 145 days (term), perfused and the corpus callosum examined light and electron microscopically. Total axon numbers were unaffected (P>0.05). However, myelination was significantly delayed. Myelinated axons were 5.7% in the experimental group and 9.2% in controls (P<0.05); conversely, unmyelinated axons were 88.3 and 83.7% (P<0.05). Myelinated axon diameter and myelin sheath thickness were also reduced (0.68 vs. 0.94 and 0.11 vs. 0.14 microm, P<0.05). Our data suggest that repeated prenatal corticosteroid administration delays myelination of the corpus callosum and that further safety data are needed to evaluate clinical practice.

Plasma levels and biochemical characterisation of circulating met-enkephalin in canine endotoxin shock.

Endogenous opioid peptides have been implicated in the pathophysiology of shock (1-5). In anaesthetised mongrel dogs, administration of E coli endotoxin caused a rise in plasma met-enkephalin-like immunoreactivity (MLI). Biochemical characterisation of MLI by gel filtration chromatography revealed various molecular forms: 31K, 8K, 3-5K and the native pentapeptide in approximately equal amounts. After enzymatic treatment of column fractions the 31K form predominated (90.7%). This is the first demonstration of elevated MLI in endotoxin shock.

Recurrent wheezing in very preterm infants.

AIMS: To document the prevalence of, and identify risk factors for, recurrent wheezing treated with bronchodilators in the first year of life. METHODS: Parental history and neonatal data were collected prospectively in a regional cohort of very preterm infants (< 33 weeks). Data on maternal smoking, siblings at home, breast feeding, respiratory symptoms, and hospital re-admissions were documented at 12 months. RESULTS: Outcome data were available for 525/560 (95%) of survivors. The incidence of recurrent wheeze was 76/525 (14.5%) in very preterm infants and 20/657 (3%) in a cohort of term newborns. Significant risk factors for recurrent wheeze in very preterm infants were parental history of asthma, maternal smoking, siblings at home, neonatal oxygen supplementation at 28 days, 36, and 40 weeks of gestation. CONCLUSIONS: Wheezing respiratory illnesses are common in very preterm infants. The factors involved are similar to those in more mature infants, with the addition of immaturity and neonatal lung injury.

Maternal cigarette smoking during pregnancy, low birth weight and subsequent blood pressure in early childhood.

Given the widely acknowledged inverse relationship between birth weight and blood pressure, a raised blood pressure in the offspring of smoking mothers as compared to those whose mothers did not smoke, would be anticipated by virtue of the reduction in birth weight associated with smoking during pregnancy. The objective of the present study was to test the hypothesis that maternal cigarette smoking during pregnancy has an effect on blood pressure in childhood independent of its effect on birth weight. Data was obtained from a prospective cohort study of 1708 pregnant women and their singleton offspring, delivered live at term, in Perth, Western Australia, commenced at 16 weeks gestation with serial blood pressure measurements through early childhood. Statistically significant associations were found between maternal smoking during pregnancy and systolic blood pressure at age six, between birth weight and systolic blood pressure at ages three and six, and between maternal smoking during pregnancy and birth weight. The relationship between birth weight and blood pressure in early childhood differed significantly on the basis of maternal cigarette smoking or not during pregnancy. This differential relationship persisted after adjustment for the child's current weight and socio-economic status. We concluded that intra-uterine exposure to maternal cigarette smoking increased children's blood pressure at age one through to age six. This was not wholly attributable to an effect on birth weight or confounding of the association between birth weight and subsequent blood pressure by the child's current weight or socio-economic factors. Furthermore, maternal smoking during pregnancy does not account for the acknowledged elevation in blood pressure associated with low birth weight. The present study is an exploration of a possible causal pathway underlying the birth weight/blood pressure association rather than simply a confirmation of such an association which has been detailed in many other papers.

Patient-controlled epidural analgesia in labor: the addition of clonidine to bupivacaine-fentanyl.

BACKGROUND AND OBJECTIVES: Epidural clonidine has not been evaluated as a component of patient-controlled epidural analgesia (PCEA) solutions during labor. A randomized, double-blind trial was conducted to investigate the efficacy and side effects of PCEA using bupivacaine and fentanyl, with or without clonidine. METHODS: Seventy-five healthy parturients in active labor were assigned to a PCEA solution of 0.0625% bupivacaine and fentanyl 2 microg/mL (4 mL demand bolus, 15 min lockout), with or without clonidine 4.5 microg/mL. The primary outcome measure was parturient rating of analgesia; others assessments included pain scores, drug utilization, supplementation and side effects. RESULTS: Thirty-one parturients received clonidine (group BFC) and 38 received control solution (group BF). Eight (6 group BF, 2 group BFC, P = .28) failed to achieve satisfactory epidural analgesia. There was a trend for parturient ratings of pain relief to be higher in group BFC, with significantly more reporting excellent first-stage analgesia (81% v. 57%, P<.05). Pain scores were similar. Clonidine (median dose, 28 microg/h) reduced total bupivacaine and fentanyl use (P<.01), and reduced supplementation (P<.01). Maternal blood pressure (BP) and recordings of systolic BP below 100 mm Hg did not differ. Group BFC had higher sedation scores (P<.01), but no one appeared oversedated. Shivering was reduced in group BFC (P<.01). CONCLUSIONS: The addition of clonidine to epidural bupivacaine and fentanyl for PCEA in labor improved analgesia, reduced the supplementation rate, and reduced shivering. Increased sedation and lower BP were not clinically important.

Effect of nappy liners on temperature stability in very preterm infants.

OBJECTIVE: To determine whether absorbent liners used in posturally supportive cloth nappies influence temperature stability in infants < 31 weeks gestation. METHODOLOGY: Randomized cross-over trial conducted at King Edward Memorial Hospital for Women, Perth, Western Australia. Twenty-three infants nursed in incubators on Infant Servo Control were randomly assigned to wear cloth postural support nappies alternately with or without absorbent liners for 24-h periods over 4 days. Measurements of skin and incubator temperatures were recorded hourly. Times of all nappy changes and infant handling procedures were also recorded. RESULTS: There was no change in any temperature measurement over time, between days, or between day/night periods. Infants nursed with the liner demonstrated a higher skin temperature (0.04°C), and a lower incubator temperature (1.05°C). A drop in skin temperature of 0.02°C and an increase in incubator temperature of 0.28°C occurred following handling of infants. There was no effect due to sex, gestational age, or actual age of the infants. CONCLUSION: Use of an absorbent liner within a cloth postural support nappy promotes better temperature regulation in infants < 31 weeks gestation, by reducing incubator temperature and increasing skin temperature.

The progression of disease stage in twin-twin transfusion syndrome.

OBJECTIVE: To estimate the frequency of progression or regression of disease stage in pregnancies complicated by twin-twin transfusion syndrome (TTTS) managed with non-placental laser techniques. METHODS: A cohort of TTTS pregnancies within the sole perinatal center for the state of Western Australia was examined. All cases of prenatally identified TTTS from 1992 to 2002 were staged at diagnosis (retrospectively prior to 2000, prospectively since). Amnioreduction and septostomy were the principal therapies used. Features associated with progression, regression or stability were identified. RESULTS: During the study period, 71 cases of TTTS were managed. Amnioreduction was performed in 73.2%, with no difference in the median number of procedures by stage (p = 0.178). In 21.1% of cases, TTTS resolved completely with persistent normalization of amniotic fluid volumes after amnioreduction (median number of procedures: 2). Disease resolution was associated with pregnancy prolongation, greater gestational age at delivery (36 weeks vs. 28.4 weeks, p < 0.001) and increased perinatal survival (100% vs. 42.6%, p < 0.001) compared with stage progression. Logistic regression analysis predicted that the probability of both infants surviving was 80% if the pregnancy remained at Stage I or II throughout, compared with a probability of 50% if it reached Stage III or more at 26 weeks, and only 25% if the disease reached Stage III or more at 16 weeks' gestation. CONCLUSION: Pregnancy outcome for TTTS managed with amnioreduction techniques is correlated with stage at diagnosis and the subsequent disease evolution. However, the progression of stage in TTTS is unpredictable and the likelihood of spontaneous fetal demise was not different between stages.

Effectiveness and safety of a structured swimming program in previously sedentary women during pregnancy.

OBJECTIVE: To determine whether undertaking a swimming program in sedentary women during pregnancy would improve maternal fitness without adverse fetal consequences. METHODS: Prospective observational investigation of healthy sedentary pregnant women participating in a monitored swimming program. RESULTS: Twenty-three women attended swimming sessions from 16 to 28 weeks of gestation resulting in increasing distances swum and improved aerobic fitness as measured by physical work capacity (PWC170) (p = 0.003). Resting maternal heart rate decreased (p = 0.041) and resting systolic (p = 0.092) and diastolic (p = 0.971) blood pressures remained unchanged over gestation. The mean fetal heart rates decreased with advancing gestational age (p = 0.001), consistent with normal physiology. Non-stress tests and umbilical artery systolic/diastolic ratios were similar before and after swimming sessions, providing evidence that fetal well-being was unchanged. CONCLUSIONS: A structured swimming program in sedentary pregnant women increases maternal fitness without any alteration in maternal and fetal well-being.

A computerized technique for vertebral morphometry.

A new technique for morphometric measurement of vertebral bodies has been described, in which a computerized image analysis system was used to digitize and measure standardized lateral radiographs of the thoracic and lumbar spine. The sources of error in the radiographic system and the image analysis system were assessed using vertebral phantoms and test images. Oblique projection in the radiographic image of a vertebra did not produce a significant error in the measured area. The radiographic magnification was approximately 35%. Optical non-uniformity was detected in the image analysis system, and was ascribed to the lens optics. The maximum intra-observer and inter-observer variations in vertebral area were 3.1% and 5.3% respectively for experienced observers. The technique is applicable to clinical studies of large populations, and has value in investigating vertebral deformity in the management of metabolic bone disease.

A prospective cohort study of the impact of domestic violence on young teenage pregnancy outcomes.

INTRODUCTION: The incidence of domestic violence among pregnant Australian teenagers is higher than rates reported for the general community. However, there are limited data that address the impact of this abuse upon pregnancy outcome. We have examined the significant antenatal associations of domestic violence in young teenage pregnancy, and the impact of this abuse upon pregnancy outcome. DESIGN, SETTING, PARTICIPANTS: A multicenter prospective cohort study was performed between January 1, 1997 and June 30, 1999. Patients were interviewed and completed questionnaires in the antenatal period to establish whether they were victims of domestic violence. Labor and delivery details were independently collated after discharge for mother and infant. Data were analyzed using an analysis of variance, with a P-value of 0.05 considered significant. RESULTS: Of 537 patients enrolled in the study, 157 (29.2%) were victims of domestic violence; 380 (70.8%) were not and acted as pregnant teenage controls. Key findings were that teenage victims of domestic violence (VDV) were more likely to smoke, drink alcohol, or use illegal drugs than controls (P < 0.0001). VDV had a higher incidence of infectious morbidity and Pap smear abnormalities (P < 0.007) and psychosocial pathology (P < 0.0001) than controls. A higher incidence of puerperal and neonatal morbidity was observed in VDV and their newborns compared to controls (P < 0.007). The estimated cost of hospital care for teenage VDV was double that of the Australian average. CONCLUSION: We need to identify all teenage mothers exposed to domestic violence and provide them with expert intervention services. Early intervention programs are likely to be cost effective.

Intrathecal fentanyl-induced pruritus during labour: the effect of prophylactic ondansetron.

Fentanyl is commonly used for spinal analgesia during labour but it is associated with a high incidence of pruritus. This randomised, double-blind, placebo-controlled study was performed to evaluate the effect of prophylactic ondansetron on the incidence and severity of pruritus among parturients receiving intrathecal fentanyl as part of combined spinal-epidural analgesia. Seventy-three women were randomised to receive either saline placebo (group P, n = 25), ondansetron 4 mg (group O4, n = 23) or ondansetron 8 mg (group O8, n = 25) intravenously before intrathecal fentanyl 25 micrograms and bupivacaine 2 mg. The incidence and severity of pruritus were measured using a verbal rating and a visual analogue scale, and by the requirement for rescue anti-pruritic medication (naloxone). The overall incidence of pruritus was 95% (group P 100%, group O4 95%, group O8 90%). There were no significant differences between groups for severity of pruritus or requirement for treatment (naloxone given to 45%, 28% and 35% of groups P, O4 and O8 respectively). Secondary outcomes such as the incidence of headache, pain and nausea were not significantly different between groups. We conclude that prophylactic ondansetron 4 or 8 mg intravenously was ineffective in reducing the incidence or severity of intrathecal fentanyl-induced pruritus during labour.

Postoperative intraspinal opioid analgesia after caesarean section; a randomised comparison of subarachnoid morphine and epidural pethidine.

A randomised, blinded clinical trial was performed to evaluate intraspinal opioid analgesic techniques after caesarean section. Healthy term parturients having elective caesarean section under combined spinal-epidural anaesthesia were allocated to one of three groups. Postoperative analgesia, including non-steroidal anti-inflammatory drugs, was provided using either pethidine patient-controlled epidural analgesia (group PCEA) or subarachnoid morphine 200 microg, the latter supplemented as required with patient-controlled intravenous pethidine (group SMPCIA) or oral paracetamol and codeine (group SMO). Maternal analgesia, side effects, recovery and satisfaction were assessed for 48 h. Of 144 parturients enrolled, 137 completed the study (PCEA n = 44, SMPCIA n = 45, SMO n = 48). The groups were demographically similar. All participants experienced good pain relief, including median visual analogue pain scores (0-100) with movement <40 between 0-24 h. However, pain scores were significantly lower at 8 and 12 h in those receiving subarachnoid morphine (P< 0.05). Women in groups receiving subarachnoid morphine experienced more severe pruritus (P<0.001), nausea (P< 0.001) and drowsiness (P< 0.05). Postoperative recovery of bowel function and ambulation occurred earlier in those using PCEA, although this did not appear to be of clinical significance. Patient satisfaction was similar, although women in group SMO were least likely to choose this approach again (P<0.05). We concluded that all three techniques provided effective analgesia for a prolonged period postoperatively. Better pain relief, but more opioid-related side effects, resulted from subarachnoid morphine 200 microg, and re-evaluation of reduced doses of subarachnoid morphine may be warranted.