Mu- and delta-opioid receptors are downregulated in the largest diameter primary sensory neurons during postnatal development in rats.

The aim of this study was to investigate the postnatal development of mu-(MOR) and delta-opioid receptor (DOR) immunoreactivity in rat dorsal root ganglia. Lumbar dorsal root ganglia (DRG) from postnatal day (P) 0, 3, 7 and 21 rat pups were immunostained for MOR and DOR. Proportions of MOR +ve and DOR +ve cells were calculated from profile counts. Diameters of MOR +ve and DOR +ve cells were measured and compared to -ve cells. The coexpression of MOR and neurofilament (NF200) in DRG over this postnatal period was also investigated. A greater proportion of cells were immunoreactive for MOR and DOR in neonatal rat DRG at P0, P3 and P7 compared to P21. At P3, 39.5+/-1.7% of cells were MOR +ve and 30.3+/-1.5% were DOR +ve, whereas at P21, the values were 30.1+/-1.7% and 21.8+/-1.6% (mean+/-SEM), respectively. During the first postnatal week both opioid receptors were expressed in cells across the whole diameter range but by 3 weeks of age, expression was restricted to small and medium diameter cells. Furthermore, a significantly higher proportion of NF200 +ve cells expressed MOR in new-born compared to P21 rats. The results show that MOR and DOR expression is downregulated in the largest diameter, NF200 +ve primary sensory neurons postnatally. Since these neurons are mainly non-nociceptive, this may explain previous reports of opioid agonists affecting reflex responses to both innocuous and noxious stimuli in rat pups. The results highlight an important difference between opioid function in the immature and adult nervous system.

Influence of peripheral inflammation on the postnatal maturation of primary sensory neuron phenotype in rats.

The influence of early peripheral inflammation upon the postnatal development of rat primary sensory neuron subtypes was investigated. Lumbar dorsal root ganglia (DRG) were immunostained for calcitonin gene-related peptide (CGRP), neurofilament (NF200), and isolectin B4 (IB4) binding. Proportions of each subpopulation were measured at postnatal day (P) 0, P3, P7, and P21 in normal pups and in those that had received a unilateral hindpaw carrageenan injection at P1. The effects were compared with those following a similar injury in adults. Both the IB4 (positive [+ve]) and NF200+ve cell populations increased postnatally (IB4+ve: 23 +/- 1.6% to 32.6 +/- 1.3%; NF200+ve: 33.8 +/- 1.2% to 43.3 +/- 1.9%), whereas the population of CGRP+ve cells stayed the same. After neonatal inflammation, the rise in IB4+ve binding occurred earlier but was the same as that in controls by P21. The CGRP+ve population increased at 2 and 6 days after carrageenan in neonates, because of an increase in both small CGRP/IB4 and larger CGRP/NF200 double-labeled cells, but was normal by 3 weeks. Carrageenan in adults caused an increase in CGRP/IB4 cells only. The effects of peripheral inflammation differ in neonatal and adult DRG. Neonatal inflammation causes CGRP upregulation in both small and large cells and accelerates the postnatal increase in IB4 binding. These effects might influence subsequent central development.

[Indications for central versus peripheral regional anesthesia]. / Differentialindikation zentraler und peripherer Leitungsanästhesien.

Serious neurological complications caused by spinal hematoma or abscess following central neuraxial block have been reported more often during the last years. In contrast, severe complications are extremely rare associated with peripheral nerve blocks. Concerned about the safety of spinal and epidural anesthesia, we encourage the use of peripheral regional techniques for procedures on the lower extremity and especially for postoperative regional analgesia. Motor block due to lumbar epidural anaesthesia using high concentrations of local anesthetic makes spinal hematoma or abscess difficult to recognize. Therefore, low concentrations of local anesthetic should be used for postoperative epidural analgesia. Any increase in motor block following neuraxial blockade should raise the suspicion of a spinal compression (e.g. hematoma or abscess). Other symptoms are back pain, radicular pain or paresthesia and incontinence. Disastrous neurological injuries can only be prevented by immediate diagnosis (MR, CT or myelography) and therapy (surgical decompression).

Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient-controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group.

UNLABELLED: The aim of our study was to compare epidural anesthesia and analgesia (EDA) with ropivacaine versus general anesthesia followed by IV patient-controlled analgesia with morphine (GA/PCA) after hip replacement regarding pain, side effects, and discharge from the postanesthesia care unit. After ethics committee approval, randomization, and informed consent, 90 patients were enrolled. In Group EDA, epidural anesthesia (ropivacaine 10 mg/mL, 15-25 mL) was followed by an epidural infusion (2 mg/mL, 4-6 mL/h for 24 h, plus top-up doses of 6-10 mL for 48 h). GA/PCA patients received general anesthesia (isoflurane/N2O/fentanyl) followed by IV patient-controlled analgesia with morphine postoperatively. Pain was assessed by using visual analog scales (0-100 mm) at rest and during physiotherapy. Pain at rest was less in the EDA (n = 43) group than in the GA/PCA (n = 45) group (at 10 h: 11.8+/-12.9 vs. 28.4+/-17.1 [P< 0.001]; at 24 h: 14.3+/-11.7 vs. 24.0+/-17 [P<0.01]; in 48 h: 14.3+/-9.3 vs. 21.1+/-17.4 [P = 0.1]). Whereas EDA patients were deemed ready for discharge from the postanesthesia care unit earlier than GA/PCA patients (5.6+/-8.9 vs. 39.7+/-41.5 min), the actual discharge time was comparable. The median time for first passage of flatus was shorter in the EDA group than in the GA/PCA group (26 vs. 47 h). Nausea and vomiting were more common in the GA/PCA group than in the EDA group (16% vs. 28% and 11% vs. 22%, respectively), whereas hypotension (11% vs. 4%) and bradycardia (14% vs. 2%) were less frequent. Under the conditions of the present study, EDA with ropivacaine provided pain control after hip replacement superior to that provided by IV patient-controlled analgesia with morphine, particularly during the first 24 h. Both approaches to pain management were equally safe. IMPLICATIONS: Compared with general anesthesia and postoperative IV patient-controlled analgesia with morphine, epidural anesthesia and analgesia with the new local anesthetic ropivacaine enables patients to be discharged sooner from a postanesthesia care unit and provides superior pain relief during the first 24 h after hip replacement.

[Spinal and regional anesthesia in bacteremia]. / Rückenmarknahe Regionalanästhesien bei Bakteriämie.

Bacteraemia and septicaemia are generally thought to be relative or absolute contraindications for central neural axis (CNA) blocks. Postulated mechanisms for haematogenous infection of the central nervous system (CNS) caused by subarachnoid or epidural puncture might be an accidental vessel puncture, a change of pressure in the subarachnoid space, and the induction of a "locus minoris resistentiae." Infectious complications of diagnostic lumbar puncture, spinal or epidural anaesthesia are very rare. Although in animals meningitis can be induced by subarachnoid puncture during bactaeremia, there is no study that proves an increased risk for bacteraemic patients. Transient bacteraemia is common, especially in urological and obstetrical-gynecological procedures that are often done in regional anaesthesia, but the incidence of infectious complications is low. This review investigates the few published cases in which a haematogenous infection of the CNS may have been caused by regional anaesthesia. Based on current knowledge, bacteraemia cannot be an absolute, but only a relative contraindication for CNA blocks. Antibiotic chemoprophylaxis should be given before the puncture and the patients must be closely followed after the anaesthesia, particularly for the development of spinal epidural abscess. Because of the possibly increased risk of infectious complications, informed consent should be obtained from the patient.

[Anesthesia and "the pill"]. / Ansthesie und "Pille".

PIP: The question concerning the effect of general anesthesia on oral contraceptives (OCs) is answered taking into consideration the modus operandi for the praxis. In theory, several interactions are possible between OCs and anesthesia: 1) the influencing of absorption through the ensuing anesthesia or postoperative vomiting; 2) the alteration of distribution volume; or 3) the accelerated elimination of active ingredients; 4) pharmacodynamic interaction between anesthesia and estrogens/progesterone at the receptor level; and 5) the influence on the endogenous hormone level through general anesthesia, which counteracts contraception. The absorption of oral antibiotics taken for endocarditis prophylaxis is not influenced 3-4 hours before a short narcosis. Similarly, undisturbed absorption of paracetamol was demonstrated, when compared to a control group, after general anesthesia without the administration of opiates. No investigations have been conducted regarding the time-specific correlation between the taking of OCs and general anesthesia. General anesthesia cannot significantly influence the distribution mechanism of estrogens and progesterones. It has been demonstrated that the clearance rate for gestagens in pregnant rats during general anesthesia is lowered, which probably can be attributed to a counter-regulation in response to a simultaneously diminished gestagen production. There are no data relating to the interaction of anesthetics and estrogen and gestagen receptors. It is likely that the coordinated increase of luteinizing and follicle-stimulating hormones through general anesthesia can be excluded. The disturbed absorption of OCs is considered to be the only significant factor whereby general anesthesia exerts an influence.^ieng

The role of atrial natriuretic factor [alpha-human ANF-(99-126)] in the hormonal and renal adaptation to sodium deficiency.

Atrial natriuretic factor (ANF) inhibits renin and aldosterone secretion and enhances natriuresis in short term experiments. For studying the role of ANF in the chronic hormonal and renal adaptation to sodium restriction, we infused alpha-human ANF iv at a low dose (0.15-0.2 microgram/min) for 6 days into five normal male volunteers on a low sodium diet (LS; 15 mmol Na+/day) to mimic ANF levels observed in a preceding high sodium period (HS; 250 mmol/day). Endocrine (ANF, PRA, and aldosterone) and renal parameters (urine volume and urinary sodium) and plasma and urinary cGMP were measured and compared to sodium restriction without ANF infusion. At the end of HS and LS periods, the response of plasma aldosterone to angiotensin-II infusion was tested. ANF infusion prevented the fall in plasma ANF from a mean of 17.7 on HS to 7 pmol/L on LS by raising the level to 16.1 pmol/L. Cumulative negative sodium balance and the rise in renin activity and aldosterone were almost identical in both parts of the experiment. There was a transient diuretic and mild hypotensive effect of ANF. Plasma and urinary cGMP rose only transiently during ANF infusion despite constantly elevated ANF levels, suggesting that the effect of ANF was blunted under long term conditions by receptor down-regulation or other mechanisms inhibiting cGMP formation. Chronic ANF infusion did not blunt the enhanced aldosterone response to angiotensin-II in the LS state. ANF does not seem to play a major role in the long term renal and hormonal adaptation to dietary sodium restriction.

Effects of atrial natriuretic factor on the renin-aldosterone system: in vivo and in vitro studies.

We investigated the effect of high physiological plasma levels of human varies; is directly proportional to atrial natriuretic factor (ANF) on renin and aldosterone secretion in normal sodium deplete men. In short term infusion studies (2 or 8 h duration), ANF plasma levels as observed after sodium loading (50-70 pg/ml) lowered basal renin (PRA) and aldosterone, but had only a marginal effect on angiotensin II-stimulated aldosterone secretion. Preliminary results of a study with long term infusion (6 days) of ANF during a period of dietary sodium depletion argue against a significant tonic inhibitory effect of ANF on the renin-aldosterone system in the preceding period of sodium repletion: the plasma aldosterone response to sodium depletion was similar with and without ANF infusion. The second messenger of ANF for the direct inhibition of aldosterone secretion from zona glomerulosa cells is still unknown. To test the hypothesis, that cGMP is the second messenger of ANF, we produced a rise in intracellular cGMP in rat and rabbit zona glomerulosa cells using the unspecific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) and the more cGMP specific phosphodiesterase specific inhibitor M + B2948 (Zaprinast). Both inhibitors simulated the action of ANF in suppressing steroid secretion and elevating cGMP levels. The results are compatible with the view that cGMP is of importance as a second messenger for ANF in adrenal zona glomerulosa cells. Selective inhibition of phosphodiesterases in combination with endopeptidase inhibition may be an interesting principle to enhance the action of endogenous and exogenous ANF.