Cerebrospinal Fluid Analysis in Recumbent Adult Dairy Cows With or Without Spinal Cord Lesions.

BACKGROUND: Diagnosis of central nervous system (CNS) lesions in recumbent dairy cattle (RDC) is challenging because neurologic examination is limited and medical imaging often is challenging or unrewarding. Cerebrospinal fluid (CSF) analysis is useful in the diagnosis of CNS disorders in cattle. However, its utility in identifying spinal cord lesions in RDC remains to be evaluated. HYPOTHESIS/OBJECTIVES: We hypothesized that CSF analysis would discriminate between RDC with and without spinal cord lesions. ANIMALS: Twenty-one RDC with spinal cord lesions (RDC+) and 19 without (RDC-) were evaluated. METHODS: Spinal cord lesions were confirmed at necropsy. Signalment, clinical findings, and CSF results were compared retrospectively. Total nucleated cell count and differential, protein concentration, and red blood cell count in RDC+ and RDC- were compared. RESULTS: Neoplasia, trauma, and infectious processes were the most frequent spinal cord lesions identified. Cerebrospinal fluid protein concentrations and TNCC were significantly higher in RDC+ compared to RDC- (P = .0092 and P = .0103, respectively). Additionally, CSF protein concentrations and TNCC in RDC- were lower than previously published reference ranges. Using an interpretation rule based on CSF protein concentration and TNCC, it was possible to accurately identify 13 RDC with spinal cord lesions and 6 RDC without lesions. It was not possible to determine spinal cord status in the remaining 18 RDC. CONCLUSIONS AND CLINICAL IMPORTANCE: Cerebrospinal fluid analysis is valuable in the evaluation of spinal cord status in RDC. The prognosis associated with these findings remains to be determined.

Ultrasonographic Examination of the Spinal Cord and Collection of Cerebrospinal Fluid from the Atlanto-Occipital Space in Cattle.

Ultrasonography is useful for the visualization of the spinal cord and associated structures and facilitates the safe collection of cerebrospinal fluid from the atlanto-occipital space in cattle. This technique is less stressful than the blind puncture technique because it does not require strong ventroflexion of the head. Furthermore, painful puncture of the spinal cord can largely be avoided when ultrasound guidance is used.

Ultrasonographic examination of the spinal cord and collection of cerebrospinal fluid from the atlanto-occipital space in cattle.

BACKGROUND: This study describes the ultrasonographic appearance of the atlanto-occipital space and ultrasound-guided collection of cerebrospinal fluid (CSF) in cattle. The atlanto-occipital space of 73 euthanized cattle (group A) and 14 live cattle with neurological disorders (group B) was examined in the sagittal and transverse planes using a 5.0-MHz convex transducer. Optimal ultrasonograms were frozen on the screen and various variables were measured in both planes using the electronic cursors. Puncture of the subarachnoid space was achieved using a spinal needle introduced in the median plane in a caudoventral direction while the spinal cord was viewed in longitudinal section. The examination of cerebrospinal fluid (CSF) was limited to gross evaluation and a red blood cell count. RESULTS: The spinal cord and the subarachnoid space were seen in the sagittal plane in all cattle. In group A, the mean distance between the skin and subarachnoid space was 38.6 mm, the mean depth of the subarachnoid space dorsal and ventral to the spinal cord was 8.9 mm and 8.4 mm, respectively, the mean diameter of the spinal cord was 9.9 mm and the mean diameter of the dural sac was 26.9 mm. These measurements were similar on transverse images. For collection of CSF from the subarachnoid space, the spinal cord was viewed in longitudinal section. All CSF samples from group A were colourless and clear and the median erythrocyte count was 2.5/µl. Ultrasonographic findings and results of CSF analysis were similar in group B. CONCLUSIONS: Ultrasonography is useful for the visualisation of the spinal cord and facilitates the safe collection of CSF from the atlanto-occipital space in cattle.

Effect of feed restriction on metabolites in cerebrospinal fluid and plasma of dairy cows.

Endocrines and metabolites in the circulation act as long-term hunger or satiety signals in the brain during negative energy balance and play an important role in the control of feed intake. These signals also occur in the cerebrospinal fluid (CSF), which surrounds the hypothalamus and brainstem: 2 major centers of feed intake regulation. Thus CSF functions as a transport medium for fuel signals between blood and brain. The CSF metabolite concentrations are mainly under control of the blood-brain barriers, which provide specific carrier molecules facilitating the entry of substances required by the brain and protect the brain from factors that could impair neuronal function. The transport of small molecules such as amino acids (AA) across the blood-brain barriers may be limited by competing AA that share a common transporter for the uptake into brain. Consequently, CSF metabolite concentrations differ from those in blood. Thus it appears likely that central (CSF) rather than peripheral (blood) metabolites act as pivotal signals for the control of feed intake. However, the contribution of putative orexigenic and anorexigenic signals in CSF of cows has not been studied so far. Therefore, the aim of this study was to elucidate associations existing between both plasma and CSF metabolites, each in response to feed restriction-induced negative energy balance. Seven German Holstein dairy cows, between 87 and 96 DIM of the second lactation (milk yield, 27.9 L/d) were fed ad libitum (AL) for 4 d and CSF from the spinal cord and blood from the jugular vein was withdrawn before morning feeding at the fifth day. Subsequently, animals were feed restricted (R) to 50% of the previous AL intake for 4 d and CSF and plasma were collected at the ninth day. Body weight, feed intake, water intake, and milk production were determined. Thirty-one AA, ß-hydroxybutyric acid, cholesterol, glucose, lactate, nonesterified fatty acids, urea, and osmolality were measured in both CSF and plasma, whereas free fatty acids and volatile fatty acids were determined in plasma only. Although plasma arginine (132%), leucine (134%), lysine (117%), nonesterified fatty acids (224%), and cholesterol (112%) increased, tryptophan and carnosine decreased (-33% and -20%, respectively) in R animals as compared with AL animals. In CSF, concentrations of these metabolites were not affected after R feeding, suggesting that these identified plasma metabolites have only little potential to contribute to central feed intake regulatory signaling in cows. By contrast, in CSF, serine, threonine, and tyrosine decreased (-20, -24, and -31%, respectively) after R feeding. Therefore, these 3 AA are potential centrally acting anorexigenic signals in cows.

Analysis of cerebrospinal fluid from 20 calves after storage for 24 hours.

Samples of CSF collected from 20 normal healthy calves were analysed either immediately or after having been stored for 24 hours at 4 degrees C in the presence of 11 per cent autologous serum. There were no significant differences between the total and differential cells counts of the fresh and stored samples, but there was a positive linear correlation between them. There were some morphological changes to the nuclei of the mononuclear cells in the stored samples.

Concentrations of ketone body and antidiuretic hormone in cerebrospinal fluid in response to the intra-ruminal administration of butyrate in suckling calves.

The aim of the present study was to elucidate the mechanism by which ketone bodies increase antidiuretic hormone (ADH) secretion. Four male Holstein calves (5 weeks of age) were utilized. Four levels of butyrate (0 g, 11 g, 22 g and 44 g) were administrated intra-ruminally in a 4 x 4 Latin square design and cerebrospinal fluid (CSF, six-position lumbar puncture), blood plasma and urine were collected. The concentration of total plasma and CSF protein was 5.5-5.6 g/dL and 27.5-28.3 mg/dL, respectively. CSF concentrations of a specific ketone body, 3-hydroxybutyric acid, were significantly higher in the 22 g and 44 g butyrate groups than in the control group. CSF concentrations of ADH in the 11 g and 44 g butyrate groups were significantly higher than in the control group. Plasma concentration of 3-hydroxybutyric acid was increased by intraruminal administration of butyrate within 15 min in a dose-dependent manner, and it was higher in the 22 g and 44 g butyrate group than in the control group from 15 min to 4 h. With the exception of the 11 g butyrate group, plasma concentrations of ADH also increased in response to butyrate treatment, and it was higher in the 44 g butyrate group than in the 22 g butyrate group from 15 min to 1.5 h. The duration of the elevated plasma concentrations of ADH was shorter than that of the plasma concentration of 3-hydroxybutyric acid. The relationship between the plasma concentrations of ADH and 3-hydroxybutyric acid was statistically significant but the correlation between the two concentrations was not high. Butyrate treatment elevated the plasma concentration of ADH and also resulted in reduced urine volume and increased urine osmolality. Haematocrit (Ht) values, and the osmolality of CSF and plasma were not different among the groups. Our results suggested that the increased ADH secretion observed in suckling calves fed dry feeds was caused by butyrate-derived ketone body that crossed the blood-brain barrier rapidly.

Cerebrospinal fluid S-100B concentrations in normal and diseased cattle.

We measured the concentrations of S-100B, a marker protein used in humans to detect brain damage, in the cerebrospinal fluid (CSF) of clinically normal cattle (n=15, mean age +/- SD: 31.8 +/- 37.5 months) and of cattle with various inflammatory disorders (n=43, 70.6 +/- 31.9 months). The mean +/- SD CSF S-100B level was 2.9 +/- 1.6 ng/ml in the normal group and 7.0 +/- 7.4 ng/ml in the diseased group. Thirteen diseased cattle that had developed no obvious neurological signs showed abnormally high S-100B concentrations (> 8.0 ng/ml), whereas the two cattle with neurological disorders did not. No particular disease could be related to the S-100B rise. Therefore, it remains inconclusive whether measurement of CSF S-100B concentration is useful in veterinary neurological diagnosis.

Receptor-mediated transport of lactoferrin into the cerebrospinal fluid via plasma in young calves.

Milk, especially colostrum, contains different kinds of macromolecules abundantly, such as immunoglobulin G (IgG), lactoferrin (Lf), transferrin (Tf), and growth factors. These are essential for the development and maintenance of health, which greatly depends on the absorption and transportation of macromolecules to the target organs. To evaluate the macromolecular transport, and concentrations in plasma and cerebrospinal fluid (CSF), colostrum was fed to newborn calves followed by milk and milk replacer, and maintained up to the 4th week under farm conditions. Plasma and CSF were collected at different times, and were analyzed for Lf, Tf, IgG and iron concentrations. Lf, Tf and IgG concentrations were steeply increased in plasma and CSF after colostrum feeding, and fluctuating patterns were observed during the experiments. Furthermore, intraduodenal administration of bovine Lf alone in young calf experiments revealed that the Lf concentration reached a peak at 4 hr, and was 7 and 4 times higher than preadministration in plasma and CSF, respectively. To explore the transport mechanism of Lf into CSF in young calves, epithelial membranes of the choroid plexus were prepared and a binding assay for Lf receptors (Lf-R) was carried out with 125I-Lf. The saturation kinetics revealed that the Bmax of epithelial membranes was 26.15 nmol/mg protein with a Kd of 0.11 microM, which also showed that Lf-R is saturable and specific. Scatchard plot transformation showed the presence of a single type of Lf-R in the choroid plexus. These results suggest that Lf is transported into the CSF through receptor mediated transcytosis in young calves, and that Lf may play an important role(s) in brain function.

[Reference values in the cerebrospinal fluid of calves between four and eight weeks of age]. / Referenzwerte im Liquor cerebrospinalis bei Kälbern im Alter von vier bis acht Wochen.

Reference values for the following parameters were established in the cerebrospinal fluid of 27 calves between four and eight weeks of age: specific weight, protein concentration, erythrocyte count, total leucocyte count with cell differentiation, creatin kinase activity, glucose and sodium. If possible, the findings were compared with those of other authors in calves and adult bovines. With 24.3 cells per microliter the 90% quantile of the total leucocyte count was seated significantly above comparable values for adult bovines. Hence, in individual cases markedly higher leucocyte counts can be expected in the cerebrospinal fluid of calves. In agreement with other authors, the protein concentration in calves was lower than in adult bovines. The reference range for creatin kinase activity was increased whereas the one for sodium was only slightly increased compared to earlier investigations in calves and in adult bovines.

Transport of colostral macromolecules into the cerebrospinal fluid via plasma in newborn calves.

The objective of this study was to investigate the transfer of bovine colostral macromolecules especially the lactoferrin (Lf), transferrin (Tf), immunoglobulin G (IgG), and epidermal growth factor (EGF) from the gastrointestinal tract to the cerebrospinal fluid (CSF) via systemic circulation in newborn calves. Cannulae were placed into the jugular vein and cisterna magna to collect blood and CSF, respectively at various time points. The colostrum, plasma, and CSF were analyzed by ELISA, SDS-PAGE, two-dimensional PAGE, and Western blotting. The concentration of total protein, Lf, Tf, and IgG in plasma averaged 47 mg, 204 ng, 101 microg and 15 microg/ml before colostrum feeding and increased to the peak values of 64 mg, 2413 ng, 820 microg, and 4608 microg/ml 8 h after feeding, respectively. Before colostral feeding CSF, total protein, Lf, Tf, and IgG averaged 0.44 mg, 10.3 ng, 0.31 microg, and 0.11 microg/ml, but peak values after feeding averaged 2.0 mg, 173 ng, 71 microg and 72 microg/ml after 10 h, respectively. Immunologically, six EGF-positive protein bands were detected in colostrum as well as in three bands higher density in plasma and CSF after colostral feeding. This study revealed that the colostral macromolecules were not only absorbed into the systemic circulation, but also some of them including Lf, Tf, IgG, and EGF-like proteins were transported into the CSF in a time-dependent manner through blood-CSF or blood-brain barrier of the newborn calves.

Macro- and trace element concentrations in blood plasma and cerebrospinal fluid of dairy cows exposed to electric and magnetic fields.

Eight multiparous, nonlactating pregnant Holstein cows (at 198 +/- 35 days of gestation and weighing 608 + 24 kg) and seven nonlactating nonpregnant ovariectomized heifers (weighing 370 + 29 kg) were confined to wooden metabolism crates in an electric and magnetic field chamber. Subarachnoidal catheters were inserted before the activation of the electric and magnetic fields. For 30 days, cows and heifers were continuously exposed in separate trials to electric and magnetic fields (60 Hz, 10 kV/m, and 30 microT). Blood plasma and cerebrospinal fluid samples were collected for 3 consecutive days before the exposure period, the last 3 days of the exposure period, and for 3 days starting 5 days after the exposure period. Concentrations of Ca, Mg, Cu, Zn, Fe, Mn, Na, P, and K in blood plasma and cerebrospinal fluid were determined. Exposure to electric and magnetic fields resulted in decreased concentrations of Mg in blood plasma and in increased concentrations of Ca and P and decreased concentrations of Fe and Mn in cerebrospinal fluid.

Effects of electromagnetic fields on the levels of biogenic amine metabolites, quinolinic acid, and beta-endorphin in the cerebrospinal fluid of dairy cows.

Eight multiparous non-lactating pregnant Holstein cows at 198 +/- 35 d of gestation, weighing 608 +/- 24 kg, were confined to wooden metabolic cages in an electric and magnetic field chamber with a 12:12 h light:dark cycle. Subarachnoidal catheters were installed 5 d before the activation of the electric and magnetic fields. The cows were exposed to electric and magnetic fields (60 Hz, 10 kV/m and 30 microT) continuously except for the feeding and cleaning time for an average of 21.44 +/- 1.4 h per day for a period of 30 d. Cerebrospinal fluid samples were collected on three consecutive days before an exposure period of 30 d, on the last 3 d of the exposure period, and for 3 d starting 5 d after the exposure period. The concentrations of beta-endorphin, tryptophan, 5-hydroxyindoleacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethyleneglycol and quinolinic acid in cerebrospinal fluid were determined. There was a significant increase in quinolinic acid, and a trend towards an increase in tryptophan, findings consistent with a weakening of the blood-brain barrier due to exposure to the electric and magnetic fields.

Cerebrospinal fluid constituents collected at the atlanto-occipital site of xylazine hydrochloride sedated, healthy 8-week-old Holstein calves.

Cerebrospinal fluid (CSF) collected at the atlanto-occipital site and serum were obtained from 10 male, 8-week-old, Holstein calves after sedation with xylazine hydrochloride. Glucose, creatine kinase, alkaline phosphatase, urea nitrogen, creatinine, sodium, potassium, chloride, calcium, phosphorus, total protein, and albumin were determined in serum and CSF. Optical characteristics, specific gravity, total red blood cell and nucleated cell counts and differentials were also evaluated in the CSF. Additionally, CSF protein electrophoresis and immunoglobulin concentrations were determined. Then, albumin quotients (AQ) were derived. Erythrocytes were observed in 9 of 10 CSF samples. Total nucleated cell counts ranged from 0-10 cells x 10(6)/L with a mean of 3 cells x 10(6)/L. Differential nucleated cell count in the CSF consisted primarily of lymphocytes/small mononuclear cells (57%), fewer monocytes/ large mononuclear cells (38%), and scant neutrophils (4%) and eosinophils (0.05%). The concentration of sodium (134 to 139 mEq/L) was similar to that of serum, but the concentration of potassium (2.8 to 3 mEq/L) was lower than that of serum. Creatine kinase activity (0 to 4 U/L) of CSF was markedly lower than serum activity. The CSF glucose concentration was approximately 80% of the serum value. Cerebrospinal fluid total protein concentration determined by electrophoresis ranged from 110 to 330 mg/L with a mean of 159 mg/L. Cerebrospinal fluid albumin ranged from 48 to 209 mg/L with a mean of 86 mg/L. In all CSF samples, radial immunodiffusion of unaltered CSF and concentrated CSF (four-fold concentration) revealed quantities undetectable by the present techniques in which the lowest standard values for IgG1, IgG, and IgM determinations was 70 mg/L and IgG2 was 30 mg/L. The albumin quotient ranged from 0.15 to 0.65 with a mean of 0.25. Based on the results of this study, CSF may be collected at the atlanto-occipital site safely and efficiently in calves, and reported values for CSF from adult cattle may not be suitable for evaluation of CSF collected from immature cattle.

[Comparative determination of creatine kinase activity in the cerebrospinal fluid and in the blood of health cattle]. / Vergleichende Bestimmung der Kreatinkinase-Aktivität im Liquor cerebrospinalis und im Blut bei gesunden Rindern.

Cerebrospinal fluid (CSF) was obtained by puncture of the canalis vertebralis at the lumbosacral foramen. The activities of creatine kinase (CK) in CSF and plasma samples of 68 healthy cattle of different age and breeds were analysed. No significant correlation between CK activities of CSF and plasma was found. The obtained CSF were classified macroscopically into groups of clear-colourless, flaky-colourless, and bloody-flaky samples. The CK activities of clear-colourless CSF showed a normal distribution and were used for further analysis. The range of standard values of CK activities in CSF (0.2-18.7 U/I) was defined after identification of runaways and narrowing of random sample to 95%.

Composition and analysis of cerebrospinal fluid in clinically normal adult cattle.

Cerebrospinal fluid and serum were obtained from 16 clinically normal adult cows (11 dairy, 5 beef). Sodium, potassium, magnesium, total protein, and albumin concentrations, osmolality, and lactate dehydrogenase and creatine kinase activities, were quantified in CSF and serum. Total and differential cell counting, protein electrophoresis, and IgG quantification were performed on CSF. Statistical analyses of these variables, including mean, SEM, range, and 95% confidence intervals, were performed. Effects of blood contamination were evaluated, and were found to be negligible for all measured constituents. Correction factors for CSF creatine kinase and lactate dehydrogenase activities accounting for cellular contamination were developed. Total nucleated cell count was similar to counts in CSF of other species, but higher than values in healthy people. Differential leukocyte count in CSF was similar to that reported in CSF of other domestic animals: mostly lymphocytes, fewer monocytoid cells, and scant neutrophils. Cerebrospinal fluid protein concentration was higher than concentration reported for dogs, goats, and people, but was similar to values reported for horses. Beef cows had higher CSF total protein concentration than did dairy cows; also, beef cows had higher CSF gamma-globulin concentration. The concentration of sodium in CSF was slightly higher than the value in serum, and potassium concentration was lower than the value in serum. In contrast to studies of human beings, CSF osmolality was generally less than serum osmolality in the cows studied. Reference values for CSF electrolyte concentrations and osmolality are useful for diagnosis of salt poisoning and for assessment of the effects of fluid therapy. Magnesium concentration was lower in CSF, compared with serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Spinal fluid concentrations of mepivacaine in horses and procaine in cows after thoracolumbar subarachnoid analgesia.

The CSF concentrations of mepivacaine in 10 Standardbred horses and of procaine in 10 Holstein cows given the drugs by thoracolumbar subarachnoid injection were determined. Mepivacaine hydrochloride was injected into the horses (502 +/- 60.5 kg) at an average dosage of 30 mg (1.5 ml of 20 mg/ml solution). Analgesia was produced 7.5 +/- 4.3 minutes after injection, extended between spinal cord segments T13 and L3 on both sides of the spinal column, and lasted 47 +/- 18.7 minutes at the T18 dermatome. Procaine hydrochloride was injected into cows (614 +/- 51.5 kg) at a dosage ranging between 75 mg and 100 mg (1.5 ml and 2 ml of 50 mg/ml solution). Analgesia was produced 8.2 +/- 2.0 minutes after injection, extended between spinal cord segments T11 and L4 on both sides of the spinal column, and lasted 47 +/- 17.5 minutes at the T13 dermatome. The critical CSF concentrations of local anesthetics required to eliminate response to pinprick stimulation were 204.4 +/- 90.3 micrograms of mepivacaine/ml in horses and 197.0 +/- 86.1 micrograms of procaine/ml in cows. Average CSF concentrations at 120 minutes after injections were made were 16.8 +/- 15.5 micrograms of mepivacaine/ml and 30.6 +/- 17.1 micrograms of procaine/ml. In in vitro experiments to determine the rates of hydrolysis of mepivacaine and procaine in CSF, significant changes (P greater than 0.05) were not seen in the CSF concentrations of mepivacaine in horses and procaine in cattle after a 120-minute incubation (37 C). The analgesic threshold concentrations of mepivacaine in CSF of horses and procaine in CSF of cows were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Restricted dietary chloride and sodium bicarbonate supplementation in early lactation Holstein cows: cerebrospinal fluid electrolyte alterations.

As part of an experiment designed to study the acute and chronic metabolic changes associated with dietary chloride (Cl) restriction and sodium bicarbonate (NaHCO3) supplementation in cows in early lactation, base-line and final experimental CSF specimens were collected to evaluate the relative effects of a nutritional Cl deficiency on serum and CSF electrolyte concentrations. Attention was paid to the comparative alterations in serum and CSF Cl concentrations as an indication of the potential for the choroid plexus active Cl transport mechanism to conserve CSF Cl concentrations in the face of total body Cl depletion. Serum Cl values in cows fed the restricted Cl diets decreased from 96.4 +/- 3.5 mEq/L to 83.4 +/- 4.5 mEq/L in a 2-week trial and from 106.0 +/- 2.8 mEq/L to 75.5 +/- 6.7 mEq/L in an 8-week trial, as an indication of a nutritional Cl deficiency. Healthy cows maintained CSF Cl concentrations approximately 20% higher than the serum values, whereas cows fed a diet containing 0.10% Cl and 0.70% NaHCO3 for 2 weeks maintained CSF Cl values at 134.8% of the serum Cl concentrations, and CSF Cl concentrations in cows given a diet with 0.10% Cl and 0.80% NaHCO3 for 8 weeks increased to 137.2% of the serum Cl values.

Appearance of procaine in spinal fluid during segmental epidural analgesia in cows.

The concentration of procaine in the CSF of 10 adult nonpregnant cows was determined after epidural injection of 5% procaine hydrochloride solution. Samples of CSF were removed through a catheter introduced into the subarachnoid space at the lumbosacral intervertebral space and advanced craniad to the same level as the epidural injection site. The position and the location of the catheter and spinal needle were confirmed radiographically. Segmental analgesia was achieved 8 to 20 minutes after completing the procaine hydrochloride injection and extended between spinal cord segments T12 and L3 on one or both sides of the animal. The average duration of analgesia, as determined by response to superficial and deep muscular pinpricks at the L1 dermatome, was 81.3 +/- 22.8 minutes (min-max, 45-127 minutes). The average subarachnoid concentration of procaine 10 minutes after epidural injection was 120.4 +/- 42.9 microgram/ml. The highest average procaine concentration recorded was 160.7 +/- 63.7 microgram/ml at 25.0 +/- 6.7 minutes after injection. Average procaine concentration was 47.8 +/- 13.5 microgram/ml at cessation of analgesia. A similar concentration of procaine was recovered from the subarachnoid space during either unilateral or bilateral analgesia. Procaine was not found in arterial plasma after the epidural administration of procaine hydrochloride. Subarachnoid threshold concentrations of local anesthetic necessary to produce spinal analgesia were reached after repeated epidural injections, but not after a single administration. It is concluded that segmental epidural analgesia is principally due to anesthesia of dura-covered nerve roots within and outside the epidural space and is minimally, if at all, dependent on the production of analgesia of nerves within the subarachnoid space.