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Capsaicin-induced sensitization of primate spinothalamic tract cells is prevented by a protein kinase C inhibitor.

Protein kinase C (PKC) has been shown to be involved in nociceptive transmission in the spinal cord. This study tested the hypothesis that induction of central sensitization in the dorsal horn by an intradermal capsaicin injection involves activation of PKC. A PKC inhibitor (NPC15437) was infused through a microdialysis fiber into the spinal cord prior to capsaicin injection. The responses of spinothalamic tract (STT) cells were recorded before and after infusion of NPC15437, and after injection of capsaicin. STT cells show an increased background activity and increased responses to innocuous stimuli following capsaicin injection while responses to heat are decreased. Spinal infusion of the PKC inhibitor, NPC15437, had no effect on background activity or responses to peripherally applied stimuli prior to capsaicin injection. However, NPC15437 prevented the sensitization of cells to weak mechanical stimuli (brush and pressure) that occurs following capsaicin injection. NPC15437 had no effect on the increased background activity or decreased responses to heat stimuli induced by capsaicin injection, suggesting alternative mechanisms for these responses. These data suggest that PKC is important for the development of central sensitization to peripheral mechanical stimuli.

Animals↗

Spinal anesthesia for cesarean delivery with dilute solutions of plain bupivacaine: the relationship between infused volume and spread.

In a prospective open study, 40 women received spinal anesthesia for cesarean delivery induced with 15 mg glucose-free bupivacaine administered in dilutions of 0.5% (3 ml), 0.25% (6 ml), 0.125% (12 ml) and 0.083% (18 ml). The solutions were infused over 30 minutes while the women lay in the right lateral decubitus. No clinical or statistical difference in the final level of block was observed between the groups. All the solutions behaved as if slightly hypobaric with the development of essentially unilateral blocks during the infusion period. At the end of the infusion period when the women were turned from the lateral decubitus to a supine tilted position, there was a sudden rise in the levels of block on both sides of the body such that, by ten minutes after turning, there was no discernible difference between the two sides. The final block levels attained were within the expected range for conventional spinal anesthesia using 2.5-3.0-ml glucose-free 0.5% bupivacaine. The findings suggest that the subarachnoid spread of isobaric/hypobaric spinal anesthetic drugs is a complex process unlikely to be explained by reference to simple models of the spinal curves.

Adult↗

Spinal monitoring during vertebral column surgery under continuous alfentanil infusion.

An anaesthetic technique for surgical procedures on the vertebral column is described consisting of a continuous infusion of a short acting opioid, alfentanil, and a muscle relaxant, vecuronium, in combination with positive pressure ventilation using a nitrous oxide/oxygen mixture. It is shown that the two standard forms of spinal monitoring, wake-up testing and somatosensory cortical evoked potentials, can be employed effectively using this anaesthetic technique. Wake-up testing was performed in 23 patients. Average wake-up time was 10 min (SD 3.7 min). Evoked responses suitable for spinal monitoring could be obtained in 60 of 61 patients.

Adolescent↗

Iron-induced lipid peroxidation in spinal cord: protection with mannitol and methylprednisolone.

The ability of the free radical scavenger, mannitol, and the synthetic glucocorticoid, methylprednisolone sodium succinate (MPSS) to reverse the effects of iron catalyzed free radical induced lipid peroxidation was assessed in the feline spinal cord. Ferrous chloride (100 mM) was infused into the gray matter of lumbar spinal cord, the region frozen in situ, removed, and homogenates of the gray matter analyzed for activity of Na+,K+-ATPase and levels of malondialdehyde (MDA). ATPase activity had declined to approximately 30% of control by 2 h after FeCl2 infusion and remained at this level through 24 h. Malondialdehyde values were elevated almost twofold at 2 h. Mannitol essentially reversed the effects of FeCl2 infusion on Na+,K+-ATPase activity and MDA production. These results may implicate the hydroxyl radical (. OH), or an oxidizing species with . OH-like reactivity, as the initiating radical species in this model of lipid peroxidation. Similarly, MPSS prevented the decline in spinal cord Na+,K+-ATPase activity and rise in MDA levels that were induced by FeCl2 infusion. This demonstrated that at the dosage levels used in this study, MPSS was an effective antioxidant. This finding provides presumptive evidence suggesting that, at least in experimental animals, the effectiveness of MPSS in preventing the tissue necrosis and paralysis that is the sequelae of spinal cord trauma may reside, in part, in the capacity of this glucocorticord to quench peroxidative reactions in the injured tissue.

Animals↗

Influence of microcatheter length on flow rates of disposable infusion kits.

BACKGROUND AND OBJECTIVE: Continuous spinal analgesia (CSA) offers considerable pain relief, and has been used in various procedures such as for surgery and cancer pain control. In Japan, portable and disposable infusion kits are increasingly employed for continuous epidural analgesia and CSA. In CSA, the use of a microcatheter is expected to reduce the incidence of spinal headache previously encountered with larger catheters. However, the flow rate of disposable infusion kits is reduced when used in conjunction with a microcatheter. METHODS: This study aimed to investigate the influence of catheter length on the flow rate of two different devices: 20- or 91-cm 28-G microcatheters connected to balloon- or syringe-type infusion pumps were examined (50 mL, 1 mL h(-1)). There were four groups each of 10 experiments: Group A: balloon-type infuser, 91 cm catheter; Group B: balloon-type infuser, 20 cm catheter; Group C: syringe-type infuser, 91 cm catheter; Group D: syringe-type infuser, 20 cm catheter. RESULTS: The mean flow rate in Group A was significantly less than that in Group B and the mean flow rate in Group C was significantly less than Group D (P < 0.05). CONCLUSION: These results indicated that the use of a shorter microcatheter achieves a better flow rate during CSA.

Analgesia, Epidural↗

Effects of TRH and high-dose corticosteroid therapy on evoked potentials, and tissue Na+,K+ and water content in experimental spinal injury.

The therapeutic effects of continuous infusion of thyrotropin-releasing hormone (TRH) and methylprednisolone (MP) in experimental spinal cord injury were studied in Swiss albino rats. Thirty rats received a 53-g clip-compression injury on the cord at T1, then were allocated randomly and blindly to one of three treatment groups (ten animals in each): (1) control; received equal volumes of saline solution; (2) MP; received 30 mg/kg methylprednisolone i.v. 1h after trauma, followed by infusion of 5.4 mg/kg/per hour i.v. for 3h; (3) TRH; received 2 mg/kg TRH i.v. 1h after trauma, followed by infusion of 1 mg/kg/per hour i.v. for 3h. MP and TRH treatments significantly improved somatosensory-evoked potentials (SEPs; P < 0.001). Both treatments significantly reduced water content, decreased Na+ content and increased the K+ content of the cord segment that included the centre of the impact (P < 0.01). Our data provide evidence for the beneficial effects of high-dose corticosteroid and TRH in promoting electrophysiological recovery and preserving spinal cord tissue following experimental injury.

Animals↗

Effects of intracerebroventricular infusion of aldosterone on blood pressure and sodium and potassium concentrations in cerebral spinal fluid in rats.

The central effects of aldosterone on blood pressure and sodium (Na) and potassium (K) concentrations in cerebral spinal fluid (CSF) were examined by chronic intracerebroventricular (ICV) infusion of aldosterone. The rats were infused for 14 days with either ICV artificial CSF, ICV aldosterone or aldosterone subcutaneously using miniosmotic pumps. ICV aldosterone increased blood pressure and lowered the K concentration in CSF. The Na concentration in CSF tended to increase, although not significantly. No significant changes in concentrations of serum Na and K, plasma renin, aldosterone, norepinephrine or ANP were observed. These results suggest that aldosterone induces blood pressure elevation through a central action, and that a change in Na or K concentration in CSF may be involved.

Aldosterone↗

Potential complications of posterior spine fusion and instrumentation in patients with cerebral palsy treated with intrathecal baclofen infusion.

STUDY DESIGN: The authors evaluated a case series of 5 patients with cerebral palsy and a previously placed subcutaneous reservoir for continuous intrathecal baclofen infusion to control spasticity who underwent spinal arthrodesis with posterior instrumentation for progressive neuromuscular scoliosis deformities. OBJECTIVES: To present our preliminary experience and complications with posterior spine fusion in patients with cerebral palsy and continuous intrathecal baclofen infusion and provide a literature review. SUMMARY OF BACKGROUND DATA: Numerous studies have reported complications associated with intrathecal baclofen infusion, many of these catheter-related. Few reports address complications associated with the intrathecal baclofen infusion, including progressive spinal deformities and complications following spinal arthrodesis. METHODS: Five patients with spastic quadriplegia cerebral palsy had spine fusions for progressive neuromuscular scoliosis. The mean age at surgery was 14.5 years. The mean preoperative major curve was 73 degrees and mean pelvic obliquity was 19 degrees . The patients' medical records were reviewed for complications following reinsertion of the intrathecal catheter following posterior spine instrumentation and arthrodesis, and for progression of the neuromuscular scoliosis, before and after intrathecal baclofen infusion was initiated. RESULTS: Two patients presented with low-pressure headaches in the postoperative period, resulting from cerebrospinal fluid leak following subarachnoid catheter reinsertion and posterior instrumentation. Four patients documented progression of the major scoliosis curve after intrathecal baclofen infusion was begun. A mean progression of 44 degrees occurred over a mean period of 11 months before the spinal arthrodesis. CONCLUSIONS: Low pressure headaches resulting from a cerebrospinal fluid leak following catheter reinsertion may occur in the postoperative period. Preoperative concerns with the baclofen pump reservoir placed subcutaneously and pressure sores were not seen with careful prone positioning on a 4-poster frame. Progression of scoliosis in patients with cerebral palsy requiring spinal arthrodesis was demonstrated in 4 of the patients after continuous intrathecal baclofen was started. The progression of the spinal deformity as a consequence of growth, natural history, or the intrathecal baclofen infusion is unknown at the present time.

Adolescent↗

Amino acid infusion induces thermogenesis and reduces blood loss during hip arthroplasty under spinal anesthesia.

UNLABELLED: The thermic effect of amino acids is augmented under general anesthesia and counteracts hypothermia. Mild hypothermia may increase surgical bleeding. We studied whether amino acids also induce thermogenesis under spinal anesthesia and whether this endogenous heat production reduces bleeding during hip arthroplasty. Rectal temperature, oxygen uptake, and perioperative bleeding were measured in 22 patients receiving an IV amino acid mixture (Vamin 18), 240 kJ/h) for 1 h before and then during spinal anesthesia and in 24 control patients receiving acetated Ringer's solution. Blood loss was calculated after surgery by weighing the swabs and the content of the suction tubes after subtraction of the saline used. After surgery, the closed drains were weighed after 24 h. In the amino acid group, the preanesthesia temperature increased by 0.4 degrees C +/- 0.2 degrees C (P < 0.01) and was unchanged in controls. At end of surgery, core temperature had decreased by 0.9 degrees C +/- 0.4 degrees C in controls and by 0.4 degrees C +/- 0.3 degrees C in the amino acid patients (P < 0.01). Oxygen uptake increased by 26 +/- 7 mL/min, or 16% +/- 5% (P < 0.05), from baseline in the amino acid patients, whereas it was unchanged in the controls. Blood loss during surgery was significantly larger in the control patients (702 +/- 344 mL) than in the amino acid patients (516 +/- 272 mL) (P < 0.05). After surgery, there were no significant differences in shed blood volume. In conclusion, amino acid infusion also induced a thermogenic response under spinal anesthesia. In addition, the prevention of temperature decrease during spinal anesthesia seemed to have a positive effect on intraoperative blood loss. IMPLICATIONS: Infusion of a balanced mixture of amino acids during spinal anesthesia prevented core body temperature decrease. Bleeding was also less pronounced.

Aged↗

Verapamil effects on physiological and behavioral responses to ethanol in the rat.

Experiments were performed to determine the ability of verapamil to reverse ethanol-induced hypothermia and behavioral changes. Permanent cannulae for intracerebroventricular (i.c.v.) infusion were implanted bilaterally in rats following standard stereotaxic procedures. Following post-operative recovery, either verapamil or artificial cerebral spinal fluid (ACSF) was infused i.c.v., followed by 4.0 g/kg ethanol in saline administered by intragastric gavage. Changes in body temperature and overall activity were monitored. In another series of experiments, rats were given either i.c.v. verapamil or ACSF followed by 1.5 g/kg intraperitoneal ethanol. Ability to turn over and open-field activity were monitored. In addition, to investigate the action of verapamil alone on body temperature, rats were infused i.c.v. either with verapamil or control ACSF, followed by intragastric administration of a volume of saline equal to 4.0 g/kg ethanol (20% v/v). At an ambient temperature of 22 degrees C, verapamil, infused prior to ethanol administration, significantly and rapidly attenuated the thermolytic action of ethanol. Central administration of verapamil alone did not induce a significant change in body temperature until more than 1.5 hr after injection, at which time temperature began to gradually increase. Pretreatment with verapamil induced significantly faster recovery from ethanol-induced changes in overall activity. Only a non-significant reversal of ethanol's effects on open-field activity and time taken to turn over occurred. These results demonstrate that verapamil can significantly antagonize ethanol-induced hypothermia and possibly motor disturbances in rats, leading us to postulate the possible involvement of neuronal Ca2+ channels in these effects of ethanol.

Alcoholic Intoxication↗

[Infusion speed as a factor to influence the analgesic level of spinal anesthesia--hypobaric solution of tetracaine].

In spinal anesthesia, as known, the injection speed of local anesthetic drug is a factor which influences the analgesic level. For study it, automatic infusion apparatus was available to control as 5 kinds of infusion speed (0.02-0.51 mL/s), and 78 patients were divided into 6 groups. The results of the painless level was discussed by T-test and distribution analysis (F-test). The mean of painless level in each group was found to be no significant difference as discussed by T-test. But the largest distribution was found in the group of 0.04 mL/s, and high analgesic level as rise up to T6 was occasionally found in groups of 0.04 mL/s & 0.02 mL/s. It means, the infusion speed is not an important factor, but extremely slow infusion is more dangerous than high speed infusion, which will take a risk of high level spinal anesthesia.

Adult↗

Amygdalar NMDA receptors control the expression of associative reflex facilitation and three other conditional responses.

Four conditional responses (CRs) were measured in rats implanted with bilateral cannulas in the basolateral nuclear complex of the amygdala (BLA). During retention testing in either the original training context or a shifted context, BLA was infused with artificial cerebral spinal fluid (ACSF) or ACSF containing an N-methyl-D-aspartate receptor antagonist (APV). Regardless of the testing context, APV infusion into BLA completely blocked the expression of conditional eyeblink facilitation and significantly attenuated the expression of conditional freezing, ultrasonic vocalization, and defecation. Discriminant analysis found eyeblink facilitation to be comparable to freezing in predicting group membership (APV vs. ACSF) and both to be better predictors than the other two CRs. The APV effect did not depend on the exact cannula positions within BLA.

Amygdala↗

Fos, RVLM-projecting neurons, and spinally projecting neurons in the PVN following hypertonic saline infusion.

Hypertonic saline (HTS; 1.7 M) infused intravenously into conscious rats increases the production of Fos, a marker of cell activation, in the hypothalamic paraventricular nucleus (PVN). The parvocellular PVN contains subpopulations of neurons. However, which subpopulations are activated by HTS is unknown. We determined whether PVN neurons that innervate the rostral ventrolateral medulla (RVLM) or the spinal cord (important autonomic sites) expressed Fos following HTS. Experiments were performed 24-96 h after chronic implantation of an intravenous cannula. HTS significantly increased the number of Fos-positive cells. In the parvocellular PVN, the maximum number of Fos-positive cells occurred rostral of the anterior-posterior level at which the number of neurons that projected to the medulla or spinal cord peaked. Compared with controls, HTS did not significantly increase the number of double-labeled neurons. These findings demonstrate that an elevation in plasma osmolality activates PVN neurons but not the subgroups of PVN neurons with projections to the RVLM or to the spinal cord.

Animals↗

Delayed Nogo receptor therapy improves recovery from spinal cord contusion.

OBJECTIVE: Myelin-associated inhibitors play a role in limiting axonal growth in the adult central nervous system. Blocking these inhibitors may promote neurological recovery from spinal cord contusion. METHODS: The soluble Nogo-66 receptor (NgR(310)ecto-Fc) protein, which can neutralize three myelin inhibitors, was infused into rats after spinal cord contusion for 28 days. Treatment was initiated intrathecally at the time of injury or 3 days after injury by the intracerebroventricular route at a dose of 0.29 mg/kg/day. Recovery of locomotion and of axonal growth was assessed. Some animals received combination therapy with NgR(310)ecto-Fc plus rolipram, a cyclic adenosine monophosphate phosphodiesterase inhibitor. RESULTS: Seven weeks after spinal injury, the Basso-Beattie Bresnahan locomotor scores were significantly improved in the 3-day delayed NgR(310)ecto-Fc treatment group (9.5 +/- 0.7; n = 16) versus the vehicle-treated group, (6.75 +/- 0.7; n = 15) (p < or = 0.01, analysis of variance). The percentage of NgR(310)ecto-Fc-treated animals able to support their weight was twice that in the control group. Delayed therapy was as efficacious as acute therapy. Addition of rolipram did not alter recovery. The beneficial behavioral effects of NgR(310)ecto-Fc correlated with sprouting of raphespinal axons in the caudal spinal cord and of corticospinal axons in the rostral spinal cord. INTERPRETATION: NgR(310)ecto-Fc treatment improves outcome in a rodent model that closely mimicked human spinal cord injury.

Animals↗

[Effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia].

Twenty patients were prospectively and randomly studied to investigate effects of infusion methods of propofol on quality of sedation and ease of sedation control during gynecological laparotomy under spinal anesthesia. After establishment of spinal anesthesia, patients were randomly assigned to one of the following two groups, i.e. conventional continuous infusion group (Cont group) and target-controlled infusion group (TCI group). In the Cont group, propofol was started at a rate of 6 mg.kg-1.hr-1 until response to command disappeared. In the TCI group, the initial target concentration of propofol was set at 1.2 micrograms.ml-1 until response to command disappeared. Thereafter infusion rate or target concentration was adjusted to maintain Mackenzie's score at 3 or 4. Predicted concentration of propofol was 1.2 +/- 0.01 micrograms.ml-1 at induction of sedation and 1.2 +/- 0.11 micrograms.ml-1 during stable sedation in the TCI group. Satisfaction VAS, anxiety VAS, discomfort VAS, sedation score and times of changing infusion condition were similar in both groups. Total dose of propofol was significantly less in the TCI group. In conclusion, quality of sedation and ease of control of sedation were comparable in both groups and continuous infusion method is simple.

Adult↗

The effects of intrathecal morphine and naltrexone on autotomy in sciatic nerve sectioned rats.

Rats were implanted with an intrathecal catheter aimed at the lumbar enlargement (LE). Morphine hydrochloride (240 micrograms/day) was infused continuously on the spinal cord for 14 days with an osmotic minipump delivering 0.5 microliter/h solution or a bolus dose of naltrexone (37.5, 75 or 150 micrograms) was injected intrathecally. Intrathecally infused morphine delivered on the dorsum of the LE induced analgesia, as tested on the hot plate, whereas normal saline was without effect. Naltrexone caused hyperalgesia revealed as decreased threshold for vocalization to electrical stimulation of the tail. Rats with unilaterally sectioned sciatic nerves that were continuously infused with morphine on the dorsum of the LE autotomized significantly less than saline controls. Nerve sectioned rats injected with naltrexone had an overall level of autotomy similar to saline controls. However, autotomy had a somewhat earlier onset and was more severe with naltrexone than with saline. It is therefore concluded that intrathecal infusion of opiates specifically reduces autotomy, a behavior that may occur as a result of chronic discomfort or pain following nerve injury. Furthermore, the endogenous opiate system at the spinal level may be involved in the control of autotomy.

Animals↗