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PubMed2000

c-Fos expression in the midbrain periaqueductal gray during static muscle contraction.

The periaqueductal gray (PAG) of the midbrain is involved in the autonomic regulation of the cardiovascular system. The purpose of this study was to determine if static contraction of the skeletal muscle, which increases arterial blood pressure and heart rate, activates neuronal cells in the PAG by examining Fos-like immunoreactivity (FLI). Muscle contraction was induced by electrical stimulation of the L7 and S1 ventral roots of the spinal cord in anesthetized cats. An intravenous infusion of phenylephrine (PE) was used to selectively activate arterial baroreceptors. Extensive FLI was observed within the ventromedial region (VM) of the rostral PAG, the dorsolateral (DL), lateral (L), and ventrolateral (VL) regions of the middle and caudal PAG in barointact animals with muscle contractions, and in barointact animals with PE infusion. However, muscle contraction caused a lesser number of FLI in the VM region of the rostral PAG, the DL, L, and VL regions of the middle PAG and the L and VL regions of the caudal PAG after barodenervation compared with barointact animals. Additionally, the number of FLI in the DL and L regions of the middle PAG was greater in barodenervated animals with muscle contraction than in barodenervated control animals. Thus these results indicated that both muscle receptor and baroreceptor afferent inputs activate neuronal cells in regions of the PAG during muscle contraction. Furthermore, afferents from skeletal muscle activate neurons in specific regions of the PAG independent of arterial baroreceptor input. Therefore, neuronal cells in the PAG may play a role in determining the cardiovascular responses during the exercise pressor reflex.

Animals↗
PubMed1999

Patient-controlled analgesia: An efficient therapeutic tool in the postoperative setting.

Patient-controlled analgesia (PCA) is one of the newer techniques for pain management. It was developed in reaction to the large number of unsatisfied postoperative patients suffering from moderate to severe pain despite the availability of potent analgesic drugs. With PCA, patients are allowed to self-administer small analgesic doses into a running intravenous infusion, intramuscularly, subcutaneously or even into the spinal space. Clinical experience soon demonstrated that individual variability in pain intensity and analgesic needs was extremely large. Psychological factors seem to be as important as the surgical trauma. Opioid consumption is usually higher than with conventional regimens, but without serious side effects. Although patients generally prefer self-control, pain relief is not necessarily better than with well-conducted conventional techniques. In addition to routine clinical pain management, PCA has proven its importance in research, e.g. for pain measurement, to determine predictors of postoperative pain, to evaluate drug interactions and the concept of pre-emptive analgesia, or for pharmacokinetic designs. PCA has been extremely important in order to change the mind of physicians and nursing staff with respect to individual pain management strategies.

Analgesia, Patient-Controlled↗
PubMed2001

Effect of neuropeptide Y (NPY) on oral ethanol intake in Wistar, alcohol-preferring (P), and -nonpreferring (NP) rats.

BACKGROUND: Neuropeptide Y (NPY) deficient mice consume more ethanol than controls, whereas NPY over-expressing mice consume less ethanol than controls. Thus, ethanol drinking may be inversely associated with NPY activity. To determine whether exogenously administered NPY would alter ethanol intake, two experiments were conducted. METHODS: A within-subject design was used with intracerebroventricular (ICV) administration of NPY or artificial cerebral spinal fluid (aCSF) into the lateral ventricles. Infusions were separated by 2 to 7 days. In experiment 1, male Wistar rats (n = 10) were tested for the effects of NPY on an intake of 5% sucrose or 8% (w/v) ethanol during daily 2-hr testing periods with food and water available at all other times. In experiment 2, male alcohol-preferring (P) and alcohol-nonpreferring (NP) rats (n = 8/line) were tested for the effects of NPY on 8% (w/v) ethanol intake. RESULTS: In experiment 1, NPY (5, 10, 20 microg) significantly increased sucrose intake relative to aCSF baseline in Wistar rats, a finding consistent with previous observations of the orexigenic effects of the peptide. However, NPY (10 microg) did not alter ethanol intake in Wistar rats. In experiment 2, NPY (5 and 10 microg) significantly decreased ethanol intake in P rats, but not in NP rats. CONCLUSION: The reduction in ethanol intake seen with the P rats is consistent with the postulated negative relationship between NPY activity and ethanol intake. The lack of effect of NPY on ethanol intake in Wistar and NP rats may be related to the lower baseline levels of ethanol intake in these rats or to differential central nervous system basal NPY activity or sensitivity to the peptide.

Alcohol Drinking↗
PubMed1990

[Disturbance of CSF absorption after experimental subarachnoid hemorrhage; correlation with subarachnoid fibrosis].

Correlation between subarachnoid fibrosis and absorption resistance of cerebrospinal fluid (CSF) after experimental subarachnoid hemorrhage (SAH) was studied in dogs. Scanning electron microscope (SEM) was used along with steady-state infusion method. Experimental SAHs were produced by injecting 0.6-1.0 ml/kg of blood into the cisterna magna singly, twice and three times for 11, 7 and 8 dogs respectively. All dogs were sacrificed by perfusing their brain with 10% formaldehyde solution immediately after completion of the measurement of CSF absorption resistance. This was conducted at various periods ranging from 3 to 7 weeks after the first blood injection. Measurement of absorption resistance was performed by infusion of physiological saline solution into the spinal subarachnoid space at speeds of 0.1, 0.2 and 0.3 ml/min for 30, 15 and 10 minutes respectively. The measurement was also conducted in 9 dogs without producing SAH as a control study. Specimens collected from basal cistern, lateral cerebral fissures and parasagittal sulci were observed in their subarachnoid spaces under SEM, and the degree of subarachnoid fibrosis was expressed by one of 5 grades for comparison with the absorption resistance in each dog. The grade of subarachnoid fibrosis significantly correlated with the absorption resistance. The absorption disturbances tended to improve after about a month along with disappearance of subarachnoid fibrosis. The results in this study suggest that subarachnoid fibrosis might be involved in inducing CSF absorption disturbances by affecting both the major and the lesser pathways of CSF.

Absorption↗
PubMed1986

Effect of prenatal iron deficiency on myelination in rat pups.

In this study, a histopathologic examination of the brain from iron-deficient or iron-supplemented rat pups was carried out. Pups were obtained from female rats, which were fed an iron-deficient or iron-supplemented diet during both pregnancy and lactation. Immediately after anesthesia and the collection of blood, pups were fixed by intracardiac infusion of 2% glutaraldehyde. Brain and cervical spinal cord were fixed, embedded in paraffin, and cut at 6-mu thickness. Myelin was identified using Luxol fast blue stain. As compared with controls (hematocrit, 30.8%), 11-day-old iron-deficient pups (hematocrit, 11.9%) showed reduced myelination in the spinal cord. Although myelination increased somewhat in the iron-deficient 17-day-old pups (hematocrit, 8.5%), the amount of myelin in the spinal cord and white matter of cerebellar folds was reduced as compared with that of the corresponding controls. These observations show the importance of prenatal iron adequacy in myelinogenesis.

Anemia, Hypochromic↗
PubMed2000

A comparison of the effects of patient-controlled analgesia with intravenous opioids versus Epidural analgesia on recovery after surgery for idiopathic scoliosis.

STUDY DESIGN: Epidural infusion was compared with standard patient-controlled analgesia (PCA) in 50 patients after surgical correction of adolescent idiopathic scoliosis with respect to certain postoperative parameters. OBJECTIVES: To compare postoperative parameters after posterior spinal instrumentation and fusion (PSIF) and to determine whether epidural infusion prolongs hospital stay or increases the risk of complications. SUMMARY OF BACKGROUND DATA: Patient-controlled analgesia and epidural infusion are both safe and effective in controlling postoperative pain after PSIF. One criticism of epidural infusion has been longer hospital stays. No study was found in the literature in which PCA was compared with epidural infusion. METHODS: The records of 50 consecutive patients who had undergone PSIF were reviewed. The epidural group consisted of 30 patients and the PCA group 20. Age, weight, degree of curve, and levels fused were evenly matched. Postoperative parameters including the day that each patient tolerated a full diet, day of independent ambulation, length of hospital stay, and pain control were compared. RESULTS: Pain control was comparable in each group. The epidural group tolerated a full diet earlier and on average were discharged 0.5 days sooner than the PCA group. Both differences are statistically significant. No significant complications were reported in either group. CONCLUSIONS: Epidural infusion of opioids with bupivacaine is safe and effective for controlling postoperative pain after PSIF without an increased complication rate when compared with PCA. In the current study, patients tolerated a full diet and were discharged from the hospital an average of 0.5 days earlier than PCA-treated patients.

Adolescent↗
PubMed2000

Increased neurosteroids synthesis after brain and spinal cord injury in rats.

We studied the effect of brain and spinal cord injury induced by fluid-percussion on the local synthesis of neurosteroids as measured by a gas-chromatographic/mass-spectrometric method. In the nervous system of sham operated rats i.v. infusion of pregnenolone (PREGN)-sulfate results in a 2-4 fold increase in PREGN, progesterone (PROG), 5alpha-dehydroprogesterone (5alpha-DHP) and 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha5alpha-THP, allopregnanolone) concentrations, as compared to vehicle treated rats. When PREGN-sulfate was infused 1, 3 or 7 days after brain or spinal cord injury it was observed a large time-dependent increase of PROG, 5alpha-DHP and 3alpha5alpha-THP levels in the peri-focal but not in the focal site. This increase in neurosteroids content may be due essentially to the glial cells hyperplasia in the peri-focal area and to an activation of the pathways involved in the metabolism of PREGN-sulfate to PROG, 5alpha-DHP and 3alpha5alpha-THP.

Animals↗
PubMed2006

A peptide c-Jun N-terminal kinase (JNK) inhibitor blocks mechanical allodynia after spinal nerve ligation: respective roles of JNK activation in primary sensory neurons and spinal astrocytes for neuropathic pain development and maintenance.

Optimal management of neuropathic pain is a major clinical challenge. We investigated the involvement of c-Jun N-terminal kinase (JNK) in neuropathic pain produced by spinal nerve ligation (SNL) (L5). SNL induced a slow (>3 d) and persistent (>21 d) activation of JNK, in particular JNK1, in GFAP-expressing astrocytes in the spinal cord. In contrast, p38 mitogen-activated protein kinase activation was found in spinal microglia after SNL, which had fallen to near basal level by 21 d. Intrathecal infusion of a JNK peptide inhibitor, D-JNKI-1, did not affect normal pain responses but potently prevented and reversed SNL-induced mechanical allodynia, a major symptom of neuropathic pain. Intrathecal D-JNKI-1 also suppressed SNL-induced phosphorylation of the JNK substrate, c-Jun, in spinal astrocytes. However, SNL-induced upregulation of GFAP was not attenuated by spinal D-JNKI-1 infusion. Furthermore, SNL induced a rapid (<12 h) but transient activation of JNK in the L5 (injured) but not L4 (intact) DRG. JNK activation in the DRG was mainly found in small-sized C-fiber neurons. Infusion of D-JNKI-1 into the L5 DRG prevented but did not reverse SNL-induced mechanical allodynia. Finally, intrathecal administration of an astroglial toxin, l-alpha-aminoadipate, reversed mechanical allodynia. Our data suggest that JNK activation in the DRG and spinal cord play distinct roles in regulating the development and maintenance of neuropathic pain, respectively, and that spinal astrocytes contribute importantly to the persistence of mechanical allodynia. Targeting the JNK pathway in spinal astroglia may present a new and efficient way to treat neuropathic pain symptoms.

Animals↗
PubMedDate not supplied

Automated intermittent epidural boluses improve analgesia induced by intrathecal fentanyl during labour.

PURPOSE: We compared the efficacy of epidural continual intermittent boluses (CIB) with a continuous epidural infusion (CEI) in prolonging labour analgesia induced by the combined spinal epidural (CSE) technique. METHODS: CSE was instituted in 42 nulliparous parturients at the L3 to 4 level with intrathecal (IT) fentanyl 25 micro g followed by an epidural test dose of 3 mL of 1.5% lidocaine. These parturients were then randomly assigned to receive either epidural CIB (n = 21) or CEI (n = 21) with 0.1% ropivacaine and fentanyl 2 micro g x mL(-1). For the CIB, 5 mL boluses were given hourly, with the first bolus 30 min postinduction. CEI at the rate of 5 mL.hr(-1) was initiated in the minute after CSE. The duration of analgesia, pain score, degree of sensorimotor block were compared. RESULTS: From Kaplan Meier survival analysis, the duration of analgesia was significantly longer in CIB (mean survival time 239 +/- SD 24 min vs 181 +/- 17, P < 0.05 using log rank test). During the first three hours postblock, the median sensory block to cold was higher in CIB (P < 0.05, Mann U Whitney test) but no difference in blood pressure was detected [P > 0.05, repeated measure analysis of variance (RMANOVA)]. The serial pain scores were lower in the CIB (P < 0.05, RMANOVA). CONCLUSION: CIB prolonged the duration and improved the quality of analgesia. CIB could have resulted in an improved spread of analgesics in the epidural space or encouraged a direct passage of infusate into the IT space. This could have also rendered a higher sensory block to cold in the CIB group. CIB is a good alternative to CEI for the maintenance of epidural analgesia after CSE.

Amides↗
PubMed2005

Spinal MR findings in continuous epidural analgesia without infection.

BACKGROUND AND PURPOSE: Spinal epidural abscesses are major complications of epidural anesthesia, and their MR features have been reported. In patients receiving continuous infusion via an epidural catheter, MR findings may mimic those of spinal epidural abscess in the absence of infection. The purpose of this study was to assess the spinal MR findings associated with continuous epidural anesthesia. METHODS: Spinal MR findings in five consecutive patients receiving continuous epidural anesthesia were retrospectively evaluated. Axial and sagittal T1- and T2-weighted spin-echo and contrast-enhanced fat-suppressed T1-weighted spin-echo images were obtained. Infection was ruled out on microbiologic analysis three patients and on follow-up in two. Each lesion was evaluated for its MR signal intensity, location, extent, delineation, and enhancement pattern. In three patients, follow-up MR imaging was performed within 5-150 days, and the images were compared. RESULTS: Posterior epidural lesions were identified in all five patients. The lesions were isointense to hypointense relative to the spinal cord on T1-weighted images, isointense relative to CSF on T2-weighted images, and well enhanced on enhanced T1-weighted images. The anomalous enhancement involved two to seven vertebral bodies. In one patient, the enhanced lesion slightly compressed the spinal cord. On follow-up MR imaging, the epidural lesions decreased in two patients and did not change in one. CONCLUSION: Continuous epidural anesthesia can result in MR findings similar to those of epidural abscess, even in the absence of infection.

Adult↗
PubMed1988

Tolerance to intrathecal oxymetazoline-induced analgesia, with paradigm-dependent cross-tolerance to intrathecal morphine.

Male, Sprague-Dawley rats, implanted with intrathecal (i.t.) catheters, were given repeated i.t. injections of morphine (40 nmol), oxymetazoline (100 nmol) or saline (10 microliter) at 12-h intervals for 3 days. Antinociception was determined 1 or 1.5 hr after each injection using the tail-flick and paw-pressure tests. Complete tolerance to i.t. morphine and oxymetazoline developed within 72 and 24 hr, respectively. Antinociception after i.t. oxymetazoline (100 nmol) in morphine-tolerant rats, and after i.t. morphine (20 nmol) in oxymetazoline-tolerant rats, was not significantly different from their respective effects in saline-pretreated rats. These data suggest an absence of cross-tolerance between morphine and oxymetazoline in the rat spinal cord. In a separate group of rats, the continuous i.t. infusion of morphine (26 nmol/hr) produced significant antinociception; tolerance to morphine developed within 36 hr. The antinociceptive effect of i.t. oxymetazoline (100 nmol) was significantly attenuated in rats pretreated with continuous i.t. morphine as compared to saline-pretreated rats. In rats pretreated with continuous i.t. oxymetazoline, cross-tolerance to morphine could not be determined due to severe adverse effects during oxymetazoline infusion. The results of this study suggest that functional cross-tolerance between morphine and alpha adrenoceptor agonists in the spinal cord cannot be excluded on the basis of repeated i.t. injection experiments alone.

Analgesia↗
PubMed1999

A study of adenosine treatment in experimental acute spinal cord injury. Effect on arachidonic acid metabolites.

STUDY DESIGN: A prospective, randomized, blinded experimental trauma study. STUDY OBJECTIVE: The effect of adenosine on arachidonic acid metabolites and lipid peroxidation was investigated in induced spinal cord injury. SUMMARY OF BACKGROUND DATA: Effects of adenosine in ischemia-reperfusion models have been studied, but no studies of adenosine's effect on direct trauma to the spinal cord have been reported. METHODS: Thirty-seven adult Wistar albino rats were randomly divided into four groups and underwent laminectomy. Group 1 underwent a sham operation. Group 2 received an intravenous adenosine infusion of 100 micrograms/kg per minute for 30 minutes. In Group 3, a standard spinal cord trauma of 50 g.cm strength was established at the lower thoracic level with a "weight-drop" technique, and Group 4 received an infusion of adenosine (100 micrograms/kg per minute) for 30 minutes after the trauma. RESULTS: Tissue prostaglandin E2 activity was significantly higher in adenosine-treated trauma groups when compared with that in other groups (P < 0.0001). The difference in tissue leukotriene C4 activity between control and trauma groups was significant (P < 0.05). Adenosine infusion after trauma limited the increases in lipid peroxidation, with the difference approaching significance at P = 0.06. The structure of myelin was well preserved in the adenosine-treated trauma group. However, the changes were irreversible in severely damaged areas. CONCLUSION: After acute spinal cord trauma, intravenous adenosine infusion of 100 micrograms/kg per minute could attenuate progression to secondary injury, but adenosine alone was not effective yet.

Acute Disease↗
PubMed2003

Management of chronic intractable angina - spinal opioids offer an alternative therapy.

The successful treatment of chronic intractable angina by spinally administered opioids via an Algomed drug delivery device (hereinafter called the pump) is reported in seven patients. All patients had at least two prior cardiac surgeries and the duration of minimally controlled chronic intractable angina varied from 5 to 19 years prior to spinally administered opioids. The duration of effective spinally administered analgesia to either the epidural (two cases) or intrathecal (five cases) spaces varied from 2 to 7 years. The opioid used was either morphine or fentanyl and the dose increase (either mg/year or microg/year, respectively) varied from 1.2 to 16. We suggest that bolus spinal morphine or fentanyl administered via the pump is a viable alternative for the effective control of angina when more established therapies have been found to provide insufficient pain relief.

Adult↗
PubMed2005

Protective use of N-methyl-D-aspartate receptor antagonists as a spinoplegia against excitatory amino acid neurotoxicity.

OBJECTIVE: Paraplegia remains a serious complication of thoracic and thoracoabdominal aortic operations. To avoid this dreadful complication, N-methyl-D-aspartate (NMDA) receptor antagonists have been examined in the ischemic or excitotoxic neuronal injury model. In the present study, we evaluated the protective efficacy of NMDA receptor antagonists that were infused segmentally after aortic clamping, as a spinoplegia, to reduce aspartate neurotoxicity in the spinal cord. METHODS: Infrarenal aortic isolation was performed in New Zealand white rabbits. Group A animals (n = 7) were pretreated with the segmental infusion of MK-801, a noncompetitive NMDA receptor antagonist, followed by segmental aspartate (50 mmol) infusion for 10 minutes. Group B animals (n = 6) received pretreatment with CGS19755, a competitive NMDA receptor antagonist, followed by the same aspartate infusion as group A. Group C animals (n = 7) received vehicle only, followed by aspartate infusion as a control group. In addition, group D animals (n = 6) were pretreated with MK-801 that was administrated intravenously 1 hour before aspartate infusion. Neurologic status was assessed at 12, 24, and 48 hours after operation by using the Tarlov score. The spinal cords were procured at 48 hours for histopathologic analysis to determine the extent of excitotoxic neuronal injury. RESULTS: Most of the animals in groups A and D revealed full recovery or mild motor disturbance. Group B and C animals exhibited paraplegia or paraparesis with marked neuronal necrosis. In the Tarlov score at 48 hours, group A animals represented better neurologic function than group C (P < .01) and similar motor function to group D animals. Severe histopathologic change was not observed in groups A and D. Animals in groups A and D showed a greater number of motor neurons than animals in groups B and C (P < .01). The difference could be due to chance between group A and D animals (P = .08). CONCLUSIONS: These results showed that the segmental infusion of noncompetitive NMDA receptor antagonist as an intraoperative spinoplegia could have a protective effect on the spinal cord neurons against excitotoxic neuronal injury in vivo. On the other hand, efficacy of the use of competitive antagonist was suggested to be limited in this model, probably because of the insurmountable obstacle of the blood-brain barrier. CLINICAL RELEVANCE: Paraplegia is a devastating complication during surgical repair of the thoracic and thoracoabdominal aortas. Excitatory amino acids neurotoxicity through the N-methyl-D-aspartate (NMDA) receptor is no doubt the pathologic hallmark of ischemic and postischemic spinal cord injury. Systemic administration of either a competitive or noncompetitive NMDA antagonist has been reported to have neuroprotective effect, in terms of preoperative treatment, with dose-related central sympathomimetic and sedative effects. Local administration, particularly of a noncompetitive NMDA antagonist, infused segmentally after aortic clamping could therefore be a potent intraoperative pharmacologic strategy to minimize the effective dose that retains NMDA antagonism without undesirable adverse effects. Our ability to reproduce this model could facilitate pharmacologic prevention or provide a new surgical technique as a spinoplegia for NMDA receptor-mediated neuronal injury.

Animals↗
PubMed2002

NK(1) receptor and its interaction with NMDA receptor in spinal c-fos expression after lower urinary tract irritation.

The role of neurokinin 1 (NK(1)) receptor and possible interaction between NK(1) and N-methyl-D-aspartic acid (NMDA) glutamatergic receptors were investigated on spinal c-fos expression after lower urinary tract irritation with acetic acid infusion in rats. At both levels of the first (L(1)) and sixth lumbar (L(6)) spinal cord, where most of hypogastric nerve and pelvic nerve afferent terminals project, respectively, the selective NK(1) receptor antagonist CP-99,994 dose dependently reduced the total number of c-fos protein (Fos)-positive cells. However, CP-100,263, the enantiomer of CP-99,994 with a very low affinity for NK(1) receptor, did not have any effect on the total number of Fos-positive cells. Coadministration of a low dose (1 mg/kg) of CP-99,994 and NMDA receptor antagonist (MK-801), either of which alone did not affect c-fos expression, significantly inhibited c-fos expression at both levels of the spinal cord. Regarding regional differences, the number of Fos-positive cells decreased significantly at all regions of the L(6) level, but only at the dorsal horn of the L(1) level. These results indicate that NK(1) receptor is involved in spinal c-fos expression after lower urinary tract irritation and that NK(1) and NMDA receptors have a synergistic interaction in the spinal processing of nociceptive input from the lower urinary tract.

Acetic Acid↗
PubMed1998

Side effects of chronic intrathecal baclofen on erection and ejaculation in patients with spinal cord lesions.

OBJECTIVE: Assess modifications of sexual function in men treated with intrathecal baclofen for spinal spasticity. DESIGN: Prospective before-after trial. SETTING: A rehabilitation department of a university hospital; follow-up was on an outpatient basis. PATIENTS: A convenience sample of nine consecutively recruited men with spinal cord injury or multiple sclerosis who were receiving intrathecal baclofen by an implantable pump; average follow-up was 44.4 months. MAIN OUTCOME MEASURES: A questionnaire focusing on: libido; ability to sustain reflexive and psychogenic erections; rigidity, evaluated by a visual analog scale; maximum duration of erection; possibility of ejaculation. RESULTS: Libido and the ability to obtain psychogenic or reflexogenic erections were not modified. However, eight patients reported a decrease of erection rigidity and/or duration. Ejaculation was possible in three cases before implantation. It disappeared in two patients, and was more difficult to obtain in the last one. It reappeared after treatment withdrawal. No differences were found between multiple sclerosis and spinal cord injured patients. CONCLUSION: Intrathecal baclofen may compromise erection and ejaculation. This effect is reversible. Patients should be informed of this effect.

Adult↗