Antinociceptive effects of systemic lidocaine: involvement of the spinal glycinergic system.

Beside their action on voltage-gated Na(+) channels, local anesthetics are known to exert a variety of effects via alternative mechanisms. The antinociceptive effect of lidocaine is well documented, yet the exact mechanism is not fully understood. Whether glycinergic mechanisms, which play a pivotal role in pain modulation, are involved in lidocaine-induced antinociception is hitherto unclear. In the present study, lidocaine was injected intravenously in rats using the formalin test for acute pain and the chronic constriction injury model for neuropathic pain. The effect of intrathecally administered d-serine (an agonist at the glycine-binding site at the NMDA-receptor), its inactive isomer l-serine, CGP 78608 (antagonist at the glycineB-site of the NMDA-receptor) and strychnine (antagonist at inhibitory glycine-receptors) on lidocaine-induced antinociception was examined. Systemically administered lidocaine was antinociceptive in both acute and chronic pain model. In the formalin test, the effect of lidocaine was antagonized by d-serine, but not by l-serine or strychnine. In the chronic constriction injury model, antinociception evoked by lidocaine was reduced by d-serine, strychnine and CGP 78608, while l-serine had no effect. These results indicate a modulatory effect of lidocaine on the NMDA-receptor. Additionally, since in our study lidocaine-induced antinociception was antagonized by both glycineB-site modulators and strychnine our results may favor the hypothesis of a general glycine-like action of lidocaine or some of its metabolites on inhibitory strychnine-sensitive receptors and on strychnine-insensitive glycine receptors.

Racemic intrathecal mirtazapine but not its enantiomers acts anti-neuropathic after chronic constriction injury in rats.

The unique noradrenergic and specific serotonergic antidepressant mirtazapine acts antinociceptive. It is optically active and currently marketed as racemate. In an animal model of acute pain it has been shown that the enantiomers exhibit differential effects: the R(-)-enantiomer showed anti-, the S(+)-enantiomer pronociceptive properties while the racemate acted antinociceptive at low doses and profoundly pronociceptive after high-dose application. Aim of the present study was to evaluate potential enantioselective effects of mirtazapine in neuropathic pain. In a chronic constriction injury model of neuropathic pain, Wistar rats were injected (+/-)-mirtazapine and the enantiomers intrathecally. All substances were dosed between 0.001 and 1mg/kg and compared to vehicle in a randomized and blinded approach. Thermal hyperalgesia and mechanical allodynia were assessed. In contrast to the acute pain results, only racemic mirtazapine exerted significant sustained analgesic effects up to 48 h. Antinociception was observed at all dosages with a maximum in the range of 0.01 mg/kg. Surprisingly, neither enantiomer was pro- nor antinociceptive at any dose or time. Our findings suggest that the synergism of both enantiomers is required to evoke a significant analgesic effect for the treatment of neuropathic pain. Our study gained no evidence for the use of either R(-) nor S(+)-mirtazapine alone. Due to the unique characteristics of (+/-)-mirtazapine and its proven efficacy in acute pain our results suggest that racemic mirtazapine may be a particularly useful antidepressant in the adjunctive treatment of chronic neuropathic pain states and could provide additional benefit to current therapeutic options.

Differential effects of spinally applied glycine transporter inhibitors on nociception in a rat model of neuropathic pain.

Changes in glycinergic neurotransmission in the spinal cord dorsal horn are critically involved in the development of pathological pain. Since the concentration of glycine in the synaptic cleft is controlled by specialized proteins, the glycine transporters GlyT1 and GlyT2, manipulation of this system might have significant effects on nociception. In the present study, we investigated the effects of the spinally applied glycine transporter inhibitors ALX 5407 (GlyT1) and ALX 1393 (GlyT2) on nociceptive behavior in the chronic constriction injury model of neuropathic pain in male Wistar rats. After implementation of neuropathy, the animals were injected with three dosages of ALX 5407 and ALX 1393 (10, 50 and 100 microg) via an intrathecal catheter (n = 8 each). Subsequently, nociceptive behavior was evaluated regarding thermal hyperalgesia (Hargreaves method) and mechanical sensitization (von Frey filaments) over 240 min after application. Inhibition of GlyT1 by ALX 5407 had differential dose-dependent effects. While the highest and the lowest concentrations were antinociceptive, the medium dose evoked pronociceptive effects. The GlyT2 inhibitor ALX 1393 was only effective in the highest concentration at which it exerted significant antinociception. However, in the same dose, ALX 1393 caused remarkable side effects such as respiratory depression and motor deficits in three animals. Our findings indicate that inhibition of glycine transporters is capable of evoking significant effects on nociceptive behavior in neuropathic pain. Whether glycine transporter inhibitors have the capability to gain clinical relevance as analgesic compounds on the long run has to be elucidated in further investigations.

Stimulating catheter as a tool to evaluate peripheral nerve function during hip rotationplasty.

OBJECTIVE: Stimulating catheters have been introduced into clinical practice to confirm perineural localization of the catheters. The muscular twitch induced over the catheter may be used to evaluate nerve function intraoperatively. Therefore, the function of the sciatic nerve was evaluated during major cancer surgery of the femur. CASE REPORT: A 7-year-old boy (29 kg) was scheduled for hip rotationplasty for resection of an osteosarcoma of the left femur under general anesthesia and postoperative pain therapy with an epidural stimulating catheter. In hip rotationplasty the femur is resected, the lower limb and foot are rotated 180 degrees and the tibia plateau is attached to the pelvic acetabulum to form a new hip joint. During preparation of the left thigh and the sciatic nerve, motor responses to stimulation of the catheter were preserved, but the stimulation threshold increased. After vascular anastomosis the foot remained cold, therefore ropivacaine was applied epidurally and subsequently a warming of the foot was observed. At the end of the operation, the patient was free of pain, a good capillary pulse of the leg was observed, and the patient was able to move the foot and toes of the rotated leg. CONCLUSIONS: The use of epidural stimulating catheters as a tool to monitor nerve function is a novel and simple procedure to monitor nerve function intraoperatively and to enable good postoperative pain control.

Skin temperature after interscalene brachial plexus blockade.

BACKGROUND AND OBJECTIVES: In neuraxial anesthesia, increase of skin temperature is an early sign of successful block. Yet, during peripheral nerve block of the lower extremity, increase in skin temperature is a highly sensitive, but late sign of a successful block. We hypothesized that after interscalene brachial plexus block, a rise in skin temperature follows impairment of sensation during successful nerve block and occurs only distally, as observed in the lower extremity. METHODS: In the present study, we prospectively evaluated the changes in skin temperature after interscalene brachial plexus blockade in 45 patients scheduled for elective shoulder surgery. We assessed pinprick and cold sensation as well as skin temperature at sites of the skin innervated by the median, ulnar, radial, axillary and musculocutaneous nerve. RESULTS: At the skin areas innervated by the axillary and musculocutaneous nerve, skin temperature did not increase after successful block. At the distal sites, innervated by the median, ulnar, and radial nerve, skin temperature increased significantly (1.9-2.1 degrees C within 30 min) after successful block while it did not after failed nerve block or on the contralateral side. In these areas attenuation of skin sensation preceded a measurable rise in skin temperature (> or =1 degrees C) in 56.3% of nerve blocks, occurred at the same time in 35.2%, and in 8.5% the temperature rise occurred first. CONCLUSIONS: Assessment of skin temperature cannot predict the success of an interscalene brachial plexus block of the axillary and musculocutaneous nerve. Distally, the increase of skin temperature has a high sensitivity and specificity but occurs later than the loss of sensory and motor functions. Therefore, the measurement of skin temperature during interscalene blockade is of limited clinical value.

Lidocaine induces apoptosis via the mitochondrial pathway independently of death receptor signaling.

BACKGROUND: Local anesthetics, especially lidocaine, can lead to persistent cauda equina syndrome after spinal anesthesia. Recently, lidocaine has been reported to trigger apoptosis, although the underlying mechanisms remain unknown. To elucidate the pathway of lidocaine-induced apoptosis, the authors used genetically modified cells with overexpression or deficiencies of key regulators of apoptosis. METHODS: Human Jurkat T-lymphoma cells overexpressing the antiapoptotic protein B-cell lymphoma 2 as well as cells deficient of caspase 9, caspase 8, or Fas-associated protein with death domain were exposed to lidocaine and compared with parental cells. The authors evaluated cell viability, mitochondrial alterations, cytochrome c release, caspase activation, and early apoptosis. Apoptosis was in addition investigated in neuroblastoma cells. RESULTS: In Jurkat cells, lidocaine reduced viability, associated with a loss of the mitochondrial membrane potential. At low concentrations (3-6 mm) of lidocaine, caspase 3 was activated and release of cytochrome c was detected, whereas at higher concentrations (10 mm), no caspase activation was found. Apoptosis by lidocaine was strongly reduced by B-cell lymphoma-2 protein overexpression or caspase-9 deficiency, whereas cells lacking the death receptor pathway components caspase 8 and Fas-associated protein with death domain were not protected and displayed similar apoptotic alterations as the parental cells. Lidocaine also induced apoptotic caspase activation in neuroblastoma cells. CONCLUSIONS: Apoptosis is triggered by concentrations of lidocaine occurring intrathecally after spinal anesthesia, whereas higher concentrations induce necrosis. The data indicate that death receptors are not involved in lidocaine-induced apoptosis. In contrast, the observation that B-cell lymphoma-2 protein overexpression or the lack of caspase 9 abolished apoptosis clearly implicates the intrinsic mitochondrial death pathway in lidocaine-induced apoptosis.

A single intravenous dose of prednisolone induces phosphatidylserine externalization, loss of surface marker expression and a 24-h net increase in human peripheral blood lymphocytes ex vivo.

To understand how corticosteroids act; a characterization of their effects on lymphocytes is necessary. The effect of in vivo corticosteroids on lymphocyte subpopulations, their surface molecules and externalization of phosphatidylserine (apoptosis) is examined. In a crossover study, a single, intravenous dose of 2 mg/kg prednisolone or saline was given to six male adult human volunteers. Blood samples were withdrawn before and 30 min, 2, 5, 23 and 29 h thereafter. Lymphocyte subsets were determined by FACS analysis. Externalization of phosphatidylserine was measured by Annexin-V; cell fragments were excluded by propidium iodide staining. Lymphocyte number decreased from 2,007 +/- 473 to 634 +/- 119 microl after 5 h and rose to 3,112 +/- 436 microl after 23 h. CD4, CD8 and B cell counts declined significantly after 5 h (P < or = 0.01). The expression of CD28 or CD95 on T cells and the natural killer cells were unaffected. There was a significant rebound of lymphocyte numbers above baseline 23 h after prednisolone. At baseline 9.9 +/- 3.8% of cells in the lymphocyte gate did not stain for CD3, CD20 or CD56 (referred to as "null cells"). 5 h after application of prednisolone, there was a significant increase of "null cells" (28 +/- 12%, P = 0.018). The percentage of phosphatidylserine positive CD4 cells rose from 8.1 +/- 3.3 to 19.8 +/- 8% after intravenous prednisolone, while the percentage of phosphatidylserine positive CD8, B and NK cells remained largely unchanged. Prednisolone induces a most significant depletion of CD4 cells, which to some degree is associated with apoptosis. The net increase of lymphocyte numbers 23 h after prednisolone application may be a beneficial late effect of a single i.v. prednisolone shot.

Regeneration of baroafferents after implantation into different vessels.

Regeneration of peripheral nerves involves an essential contribution by surrounding tissues. This study focuses on the role of the target tissue on the regeneration of afferent peripheral nerves. We hypothesized that nerves implanted into the appropriate target tissue regain their function, whereas they degenerate when implanted into a different tissue. Therefore, aortic nerves of rabbits were transected and implanted into arteries or veins, and their function and structure was reevaluated after 1.5, 3, and 10 months. In a subset of animals, the nerves were again severed and implanted into the other vessel. Twelve of 18 nerves implanted into arteries regained typical neurophysiological activity, but none of those implanted into veins. Two times even baroreflexes were elicited through the newly built nerve endings. The structure of the nerve endings implanted into arteries resembled baroreceptors, whereas no fiber growth was detected in veins. Morphometrically, the fiber number and diameter increased over the observed time period after implantation into arteries. Nerves implanted into veins, transected after 3 months, and then implanted into arteries also regained neurophysiological activity. Again, they rebuilt baroreceptors and significantly increased their fiber number and diameter. In conclusion, when severed baroafferents are implanted into arteries, they regenerate new baroreceptors and restore the normal myelination and fiber size of the nerve over time, whereas veins seem to inhibit nerve fiber sprouting and regeneration of severed fibers.

Uniform distribution of skin-temperature increase after different regional-anesthesia techniques of the lower extremity.

BACKGROUND AND OBJECTIVES: Skin-temperature increase is a reliable but late indicator of success during regional-anesthesia techniques. The goal of this study is to determine the distribution of skin-temperature changes during different regional techniques. Does skin temperature increase in the whole area innervated by the blocked neural structures or only in certain regions within this area with the capability to react preferentially to sympathetic block (i.e., vessel-rich skin)? Although onset time may vary between different regional-anesthetic techniques, we hypothesized that the distribution of skin warming is equal. METHODS: Skin temperature was assessed continuously by infrared thermography in 24 patients who received either combined femoral-nerve and sciatic-nerve block, epidural anesthesia, or spinal anesthesia. RESULTS: Apart from differences in time of onset, no differential spatial distribution of skin-temperature changes could be detected. The earliest and greatest rise of skin temperature occurred at the great toe (10.6 degrees C +/- 0.4 degrees C), became smaller proximally, and was negligible above the ankles, irrespective of the type and extent of block. Video-thermography revealed that cold blood flows through subcutaneous veins immediately after onset of sympathetic block and initially decreases skin temperature (0.6 degrees C +/- 0.3 degrees C) during onset of spinal anesthesia. CONCLUSION: Irrespective of the applied regional-anesthetic technique, skin-temperature changes are more pronounced distally. Thermography prevents false measurements of skin temperature above subcutaneous veins and displays flow of cold blood as the mechanism of initial skin-temperature drop after regional anesthesia. Measurements of skin-temperature increase cannot be used to evaluate the extent of analgesia or sympathetic block.

Does interscalene catheter placement with stimulating catheters improve postoperative pain or functional outcome after shoulder surgery? A prospective, randomized and double-blinded trial.

BACKGROUND: In this prospective, randomized, double-blind trial we investigated the use of stimulating catheters in patients during and after shoulder surgery; functional improvement being the primary outcome measurement. METHODS: After eliciting an adequate muscular twitch at < or =0.5 mA nerve stimulation output, the perineural catheter was advanced either blindly (conventional catheter = CC group, n = 20) or guided by stimulation via the catheter (stimulating catheter = SC group, n = 20). A bolus of 40 mL prilocaine 1% and 10 mL ropivacaine 0.75% was injected, followed by a patient-controlled infusion of ropivacaine 0.2% (8 mL/h infusion rate, bolus 2 mL, lockout time 20 min). RESULTS: Onset of motor block was faster in the SC group, whereas sensory block did not differ between groups. Median pain scores on two postoperative days were equal. Improvement of the objective shoulder function score (Constant Murley Score) 6 wk postoperatively was enhanced to a clinically relevant extent in the SC group compared to the CC group (P < 0.01). CONCLUSIONS: We conclude that the use of a stimulating catheter results in a faster onset of motor block, unaltered postoperative pain, and a significantly improved functional outcome 6 wk after shoulder surgery.

Increase in skin temperature after spinal anesthesia in infants.

BACKGROUND AND OBJECTIVES: The relatively stable hemodynamics during spinal anesthesia in infants have been attributed to a less active sympathetic nervous system in comparison with adults. Thus, the authors evaluated sympathetic block primarily by measurement of skin temperature and secondarily by determination of noninvasive blood pressure as an indirect sign of sympatholysis. METHODS: In 15 infants (postconceptual age: 45.0 +/- 4.8 weeks; weight: 4.0 +/- 1.2 kg) scheduled for repair of inguinal hernia under spinal anesthesia, skin temperature at the T4 level and at the plantar foot was measured before and after spinal anesthesia. Spinal anesthesia was induced at the L4/L5 interspace with 0.5% hyperbaric bupivacaine 1 mg/kg with 10 microg/kg adrenaline added. RESULTS: Temperature at the plantar foot after spinal anesthesia rose significantly from 33.0 degrees C +/- 1.3 degrees C to 34.7 degrees C +/- 1.4 degrees C within 10 minutes and to 35.6 degrees C +/- 0.9 degrees C after 20 minutes (P < .0001), whereas the temperature at the thorax remained constant at 35 degrees C to 36 degrees C. Systolic and diastolic blood pressure decreased by 15.9 +/- 11.4 mm Hg and 9.0 +/- 9.2 mm Hg, respectively (P < .01), but remained within normal range in all cases. CONCLUSIONS: The authors found a significant increase in skin temperature of the feet within 10 minutes as a sign of sympatholysis, whereas trunk temperature remained constant. Blood pressure decreased but remained within the normal range, despite the observed sympatholysis.

Assessment of somatosensory evoked potentials during resuscitation of a 15-year-old boy with Duchenne muscular dystrophy.

Patients with Duchenne muscular dystrophy (DMD) are likely to suffer from cardiac insufficiency. Subclinical cardiac insufficiency may decompensate intraoperatively. During spinal surgery, recording of somatosensory evoked potentials (SSEP) is the standard method of spinal cord monitoring. Assessment of SSEP has proven to be a highly prognostic measure of neurological outcome after cardiopulmonary resuscitation (CPR). In the case presented, scalp SSEP as response to stimulation of both median and tibial nerves were recorded during spinal surgery in a 15-year-old boy with DMD. The patient developed severe hypotension and circulatory collapse intraoperatively. SSEP were measured before, during and up to 3h after circulatory collapse. He was successfully resuscitated and fully recovered. Latencies of SSEP remained stable from all extremities whereas amplitudes significantly decreased during CPR, but recovered completely within 3h. The amplitudes of SSEP serve as a more sensitive marker for brain ischaemia than latencies. Stability of latencies and full recovery of amplitudes within 3h indicated sufficient CPR and predicted a good neurological recovery.

Skin temperature during regional anesthesia of the lower extremity.

Increase in skin temperature (Ts) occurs early during neuraxial blocks. However, the reliability of Ts to predict successful peripheral block is unknown. Therefore, we investigated whether an increase in Ts more than 1 degrees C precedes or follows an impairment of sensation after combined femoral and sciatic nerve block as well as after epidural anesthesia. In this prospective, nonrandomized study we determined Ts changes in 33 patients undergoing knee or foot surgery under femoral and sciatic nerve block and 10 patients undergoing epidural anesthesia. Perception and motor function were assessed every 5 min. An increase in Ts (> or =1 degrees C) at the foot occurred later after sciatic nerve block than after epidural anesthesia (10.3 +/- 2.8 versus 5.0 min; P < 0.01). Alterations of Ts at skin innervated by the femoral nerve were <1 degrees C. Ts increase preceded sensory block after sciatic nerve block in 6.6% of patients but indicated a successful block (sensitivity, specificity, and accuracy = 100%). We conclude that an increase of Ts is a reliable, but late, sign of successful sciatic nerve block. Therefore it is of limited clinical value. Ts changes after femoral nerve block are negligible and late.

Mirtazapine and its enantiomers differentially modulate acute thermal nociception in rats.

The antidepressant mirtazapine is an optically active drug and currently marketed as a racemic compound consisting of its S(+) and R(-)-enantiomers in a 50:50 mixture. As stereochemistry of antidepressants has become increasingly important to consider for the relevance of their analgesic properties, we investigated the effect of (+/-)-mirtazapine and its enantiomers in an animal model of acute thermal nociception. Wistar rats were injected intrathecal with either (+/-)-mirtazapine, R(-)-mirtazapine, S(+)-mirtazapine from 1 to 0.001 mg/kg and vehicle (0.9% NaCl), respectively. The effects on thermal paw withdrawal thresholds were monitored using the Hargreaves test. (+/-)-Mirtazapine exerted pro- and antinociceptive effects in acute thermal nociception, whereas R(-)-mirtazapine showed solely antinociceptive and S(+)-mirtazapine pronociceptive properties. These results clearly demonstrate a differential effect of (+/-)-mirtazapine and its enantiomers on nociception. As R(-)-mirtazapine exerts the antinociceptive activity of the racemic mixture it may be a putative candidate for an enantioselective use as analgesic.

PONV: a problem of inhalational anaesthesia?

Even nowadays every third or fourth patient suffers from postoperative nausea and vomiting (PONV) after general anaesthesia with volatile anaesthetics. There is now strong evidence that volatile anaesthetics are emetogenic and that there are no meaningful differences between halothane, enflurane, isoflurane, sevoflurane, and desflurane in this respect. However, when propofol is substituted for volatile anaesthetics the risk for PONV is reduced by only about one fifth, indicating that there are other even more important causes for PONV following general anaesthesia. A main causative factor might be the use of perioperative opioids, but their impact--relative to other factors including volatile anaesthetics--has never been quantified. Patient-specific risk factors have also been shown to be clinically relevant; they are therefore included in the calculation of simplified risk scores that allow prediction of a patient's risk independent of the type of surgery. Although controversial, the well-known different incidences following certain types of surgery are most likely caused by patient-specific and anaesthesia-related risk factors. There is a common consensus that prophylaxis with anti-emetic strategies is rarely justified when the risk of PONV is low, while it is warranted in case of imminent medical risk associated with vomiting or in a patient with a high risk for PONV. A recently published large multicentre trial of factorial design, IMPACT, has demonstrated that various anti-emetic strategies are associated with a very similar and constant relative reduction rate of about 25-30% and that the main predictor for the efficacy of prophylaxis is the patient's risk for PONV. Interestingly, all anti-emetics (dexamethasone, droperidol and ondansetron) work independently, so that their combined benefit can be derived directly from the single effects. The effectiveness of the anti-emetics was also independent of a variety of risk factors, including volatile anaesthetics. This means that any anti-emetic prophylaxis for PONV induced by volatile anaesthetics is equally effective. Of course, the most logical approach for prevention would be the omission of volatile anaesthetics and nitrous oxide using a total intravenous anaesthesia with propofol. However, since volatile anaesthetics are probably not the most important risk factors, it might be even better--if appropriate--to avoid general anaesthesia by using a regional, opioid-free anaesthesia if PONV is a serious problem.

The spinal antinociceptive effect of nocistatin in neuropathic rats is blocked by D-serine.

BACKGROUND: The neuropeptide nocistatin (NST) has been implicated in the modulation of nociceptive responses in the spinal cord. Depending on the dose, both pronociceptive and antinociceptive effects have repeatedly been reported. The pronociceptive effect is most likely attributable to inhibition of synaptic glycine and gamma-aminobutyric acid release and a subsequent reduction in the activation of inhibitory glycine and gamma-aminobutyric acid receptors, but the mechanisms of its antinociceptive action have hitherto remained elusive. It has recently been demonstrated that synaptically released glycine contributes to N-methyl-D-aspartate receptor activation. The authors therefore investigated whether a reduction in glycine release might also account for the antinociceptive action of NST in neuropathic rats. METHODS: The authors analyzed the effects of spinally applied NST in the chronic constriction injury model of neuropathic pain. NST was injected intrathecally from nanomolar to picomolar doses and its effects on thermal paw withdrawal latencies were monitored. Furthermore, we tested whether D-serine (100 microg per rat), a full agonist at the glycine binding site of the N-methyl-D-aspartate receptor, would interfere with the effects of NST. RESULTS: At high doses (10 nmol/rat), intrathecally injected NST was pronociceptive, whereas lower doses (1 pmol/rat) elicited antinociception. The antinociceptive, but not the pronociceptive, action was occluded by intrathecal pretreatment with D-serine. L-serine, which does not bind to N-methyl-D-aspartate receptors, affected neither the pronociceptive nor the antinociceptive effect. CONCLUSIONS: These results demonstrate that NST produces a biphasic dose-dependent effect on neuropathic pain. The spinal antinociception by NST is most likely attributable to inhibition of glycine-dependent N-methyl-D-aspartate receptor activation.

Muscle weakness and paresthesia associated with epidural analgesia in a patient with an intrathecal neurofibrolipoma as part of a tethered cord syndrome.

We report a case of a 75-yr-old female patient in whom motor deficits and paresthesias occurred after lumbar epidural analgesia. These symptoms were eventually found to be due to a tethered cord syndrome. An epidural catheter was inserted for analgesia after colon surgery. The postoperative course was characterized by fluctuating sensory and motor symptoms. A magnetic resonance imaging scan showed an intraspinal mass, which was removed by laminectomy. The presented complication is of major interest because the intraspinal tumor, which must have been present for years, became acutely symptomatic. Tethered cord syndrome is caused by a limited longitudinal mobility of the cord. It is often seen as a part of spinal closure defects and is also associated with intrathecal tumors. Typically, adult patients complain of weak legs, paresthesias of the legs, and urinary incontinence. However, our patient had denied any muscular or neurological problems or urinary incontinence during the preoperative interview. Postoperative electromyogram and electroneurography ascertained chronic neurogenic lesions of multiple lumbar and sacral nerve roots. Three months after the operation, the patient was able to walk 100 m with a crutch.

A preoperative retrobulbar block in patients undergoing scleral buckling reduces pain, endogenous stress response, and improves vigilance.

BACKGROUND AND OBJECTIVES: This study aims to test postoperative analgesia by using retrobulbar block in patients with retinal detachment surgery. METHODS: Twenty-nine patients scheduled for scleral buckling were included in this double-blind, randomized, prospective study. After induction of general anesthesia and opening of the conjunctiva, patients received either 4 mL bupivacaine 0.5% or 4 mL saline 0.9% injected into the retrobulbar space preoperatively. Heart rate and blood pressure were documented before the start of anesthesia, 10 and 50 minutes later, and 60 minutes after completion of surgery. At the same time points, 10 mL of blood were withdrawn for measurement of glucose and cortisol levels to evaluate the efficacy of retrobulbar block in eliminating humoral response. Postoperative scores for pain and vigilance were recorded 1, 6, and 24 hours after completion of surgery. The application of analgesic and antiemetic drugs was documented, as well as occurrence of nausea and vomiting. RESULTS: A preoperative retrobulbar block in patients undergoing scleral buckling reduces pain, endogenous stress response, and improves vigilance. CONCLUSIONS: Because the analgesic effect of the retrobulbar block was considerably longer than pharmacologically expected, the combined retrobulbar and general anesthesia "protects" against postoperative pain and is recommended for patients undergoing scleral buckling.

Facilitation of spinal NMDA receptor currents by spillover of synaptically released glycine.

In the mammalian CNS, N-methyl-D-aspartate (NMDA) receptors serve prominent roles in many physiological and pathophysiological processes including pain transmission. For full activation, NMDA receptors require the binding of glycine. It is not known whether the brain uses changes in extracellular glycine to modulate synaptic NMDA responses. Here, we show that synaptically released glycine facilitates NMDA receptor currents in the superficial dorsal horn, an area critically involved in pain processing. During high presynaptic activity, glycine released from inhibitory interneurons escapes the synaptic cleft and reaches nearby NMDA receptors by so-called spillover. In vivo, this process may contribute to the development of inflammatory hyperalgesia.

Preemptive analgesia: no relevant advantage of preoperative compared with postoperative intravenous administration of morphine, ketamine, and clonidine in patients undergoing transperitoneal tumor nephrectomy.

BACKGROUND AND OBJECTIVES: Preemptive analgesia often failed in the clinical arena because application of a single intravenously applied drug may not prevent nociceptive input and spinal pain processing sufficiently. We therefore used an intravenous (IV), multireceptor approach and tested the preemptive analgesic effect of the antinociceptive drugs morphine, ketamine, and clonidine given before or immediately after surgery. METHODS: A double-blind, randomized, prospective study was performed in 30 patients undergoing transperitoneal tumor nephrectomy (via median laparotomy). Standard general anesthesia procedure without opioids was used. After induction, patients were randomly allocated to receive 150 microg x kg(-1) of morphine, 150 microg x kg(-1) of ketamine, and 5 microg x kg(-1) of clonidine intravenously via a motor-driven pump within 15 minutes, either before or immediately after surgery. Patient-controlled analgesia (PCA) with the opioid piritramide (IV) was used for postoperative analgesia. Postoperative pain at rest and during induced cough was quantified by analgesic requirement and pain scores (visual analog scale [VAS]) within 48 hours. RESULTS: There was no significant difference in analgesic requirement of piritramide and pain scores at rest or during induced cough. CONCLUSIONS: In contrast to encouraging observations on the combination of antinociceptive drugs, the multireceptor approach tested here failed to exert a clinically relevant effect.