Conduction block by clonidine is not mediated by α2-adrenergic receptors in rat sciatic nerve fibers

Background and Objectives: Clonidine, an α₂-adrenergic agonist, has been shown to prolong local anesthesia. It appears that clonidine by itself produces conduction block by acting on peripheral nerves. However, whether clonidine-induced conduction block is mediated through α₂-adrenergic receptors remains unclear. The purpose of this study was to see if clonidine's nerve-blocking action was through α₂-adrenergic receptors by examining clonidine's action in the presence of α₂-adrenergic antagonists. Methods: The compound action potentials (CAPs) evoked by electrical stimuli were recorded from the isolated rat sciatic nerve in a recording chamber. Conduction block was examined by analyzing CAPs with regard to peak amplitude and time-to-peak in the presence of clonidine alone or clonidine plus α₂-adrenergic antagonist yohimbine or idazoxan. Results: Both clonidine and yohimbine produced concentration-dependent, reversible, conduction block. Based on concentration-response relationships, the 50% of effective concentration (EC₅₀) were estimated to be 1.61 ± 0.51 mmol/L (mean ± SD) for clonidine and 51.4 ± 27.2 μmol/L for yohimbine. A mixture of equal volumes of 2.07 mmol/L clonidine and 55.6 μmol/L yohimbine produced conduction block to a level close to the mean value between conduction blocks induced by 2.07 mmol/L clonidine alone and 55.6 μmol/L yohimbine alone. Addition of idazoxan, a more specific α₂-adrenergic antagonist than yohimbine, to clonidine was without effect on clonidine-induced conduction block. Conclusions: The results indicated that the mixture of clonidine and yohimbine, in which either drug inhibited impulse conduction, produced conduction block in an additive manner, and that clonidine-induced conduction block was not reversed by coapplication with a specific α₂-adrenergic antagonist idazoxan. These data suggest that clonidine's effects likely depend on mechanisms not mediated by α₂-adrenergic receptors. Reg Anesth Pain Med 2000;25:620-625.     

Effects of intrathecal bupivacaine in conjunction with hypothermia on neuronal protection against transient spinal cord ischemia in rats

BACKGROUND: Excitotoxic neuronal injury from ischemia may be reduced by local anesthetics. We investigated the neuroprotective effects of intrathecally administered bupivacaine and hypothermia in a rat model of transient spinal cord ischemia. METHODS: PE-10 intrathecal catheter-implanted male Sprague-Dawley rats were randomly assigned to one of four groups: normothermia (NT) and hypothermia (HT) groups (given 15 microl of normal saline) and bupivacaine (B) and bupivacaine-hypothermia (BHT) groups (given 15 mul of 0.5% bupivacaine). Transient spinal cord ischemia was induced by inflation of a 2F Fogarty catheter placed in the aortic arch for 12 min. The rectal temperature was maintained at 37.0 +/- 0.5 degrees C for the NT and B groups, and at 34.5 +/- 0.5 degrees C for the HT and BHT groups. Motor and sensory deficit scores were assessed 2 and 24 h after reperfusion. Lumbar spinal cords were harvested for histopathology and immunoreactivity of heat shock protein 70 (HSP70). RESULTS: After reperfusion, the motor and sensory deficit scores of the NT group were significantly higher than those of the HT (P < 0.05) and BHT (P < 0.001) groups. Significant differences were evident in the motor and sensory deficit scores between the HT and BHT groups at 24 h (P < 0.05). Neuronal cell death and immunoreactivity of HSP70 were frequently observed in the NT and BT groups, but not in the HT and BHT groups. CONCLUSIONS: These results collectively suggest that intrathecal bupivacaine does not provide neuroprotection during normothermic transient spinal cord ischemia in rats, but enhances the neuroprotective effects of hypothermia.     

Acute stress decreases inflammation at the site of infection. A role for nitric oxide

Exposure to acute stress modulates immune function. Most research regarding stress and immunity has described the deleterious effects of stress. Recent studies, however, indicate that acute stress enhances many features of innate immunity. For example, exposure to acute stress reduced the time required to resolve inflammation produced by subcutaneous injection of streptomycin-killed, benign bacteria. It is unclear if this change in inflammation would be advantageous to the organism if challenged with living, infectious bacteria. Thus, the current experiments examined the effect of acute stressor exposure on inflammation development and resolution after a naturalistic, live bacterial challenge. In addition, nitric oxide (NO), an important bactericidal mediator, was measured at the inflammatory site. Rats (F344) were exposed to acute stress (100, 5-s, 1.6 mA tailshocks) and subcutaneously injected with live Escherichia coli ( approximately 2.5 x 10(9) colony forming units [CFU]). Stressed rats attained their peak inflammatory size quicker, resolved their inflammation 10-14 days faster, experienced less bacterial-induced weight loss and released 300% greater NO at the inflammatory site than nonstressed controls. Thus, acute stress improved recovery from bacterially induced inflammation possibly due to local elevations in NO.     

Changes in magnesium concentration in the serum and cerebrospinal fluid of neuropathic rats

BACKGROUND: Central sensitization of neuropathic pain is associated with an influx of extracellular calcium via the opening of N-methyl-D-aspartate (NMDA) receptor-gated ion channels, which are usually blocked by magnesium plugs. As magnesium-deficient rats develop a mechanical hyperalgesia and intrathecal or intraperitoneal magnesium suppresses neuropathic pain, the magnesium concentrations in serum and cerebrospinal fluid may be altered in neuropathic pain. We therefore compared the magnesium concentrations in serum and cerebrospinal fluid of neuropathic rats with those in injured rats without symptoms of neuropathic pain and normal rats. METHODS: Mechanical allodynia was induced in male Sprague-Dawley rats by tight ligature of the left lumbar fifth and sixth spinal nerves. The threshold of paw withdrawal was evaluated by the up-down method using withdrawal response to stimulus with a von Frey filament on the third, seventh and 14th days. Rats with a threshold of less than 4 g were selected as the symptomatic group and compared with an asymptomatic group, an unoperated control group and a sham-operated group. On the 16th day, the Mg2+ concentrations in serum and cerebrospinal fluid were measured. RESULTS: The magnesium concentrations in the serum and cerebrospinal fluid of symptomatic neuropathic rats did not differ from those in the injured rats without symptoms of neuropathic pain, sham-operated rats and normal rats. CONCLUSION: Our results suggest that physiologic homeostasis is maintained by active transport through the blood-brain barrier despite the activation of NMDA receptor-gated ion channels. However, rats with neuropathic pain may be in a magnesium-deficient condition at the effector site, such that magnesium treatment can decrease neuropathic pain.     

Separation of long-range human TERT gene haplotypes by transformation-associated recombination cloning in yeast

The hTERT gene encoding a catalytic subunit of human telomerase contains four blocks of variable number of tandem repeats (VNTRs)--two in intron 2 and two in intron 6. The segregation of hTERT VNTRs was analysed in families, revealing that all of them were transmitted through meiosis following a Mendelian inheritance. The work reports a further characterization of the minisatellites in hTERT. We employed transformation-associated recombination (TAR) cloning to isolate parental hTERT alleles and determined the specific combination of minisatellites at each of the polymorphic sites. A long-range haplotyping of hTERT determined by TAR cloning was verified by classical Mendelian analysis. Since such a strategy can be applied for any chromosomal locus, we conclude that recombinational gene capture could greatly facilitate haplotypes analysis.     

Effects of Jaoga-Yukmiwon(R), a Korean herbal medicine, on chondrocyte proliferation and longitudinal bone growth in adolescent male rats

Externally visible growth of the body is the result of proliferation of chondrocytes and longitudinal bone growth. The effects of the Korean herbal medicine, Jaoga-Yukmiwon((R)), on the growth of adolescent rats were investigated in the present study. The proliferation ratio of chondrocytes was calculated from 5-bromo-2'-deoxyuridine incorporation during DNA synthesis. The 5-bromo-2'-deoxyuridine incorporation ratio of the control group was 21.1 +/- 3.5%, and Jaoga-Yukmiwon((R)) administration markedly increased the ratio to 34.5 +/- 4.6% (p < 0.05). The bone formation rate of longitudinal bone was estimated by labelling with tetracycline, which binds to newly formed bone. The bone formation rate in the tibia of Jaoga-Yukmiwon((R))-administered rats was increased to 405.1 +/- 4.3 micro m (p < 0.05) from 292.2 +/- 11.8 micrometer (control value). The height of the growth plate in the administrated rats was increased to 614.6 +/- 10.0 micro m (p < 0.05) from 552.3 +/- 17.1 micro m. The bone morphogenetic protein-2 immunostaining in the growth plate was also increased. These results suggest that Jaoga-Yukmiwon((R)) may promote longitudinal bone growth during the developmental period.     

Effects of Aralia continentalis on hyperalgesia with peripheral inflammation

This study aimed to determine the antinociceptive effect of Aralia continentalis extract (AC) on Freund's adjuvant-induced arthritis in rats. Adult Sprague-Dawley rats received an injection of complete Freund's adjuvant (CFA) into the articular cavity of the ankle joint, and then antinociceptive behaviors and spinal Fos expression were examined. AC was found to suppress significantly nociceptive behaviors caused by CFA injection. In addition, it also decreased adjuvant-induced Fos expression in the lumbar spinal cord induced by CFA. In conclusion, this study showed that AC produced significant antinociceptive effects on CFA-induced arthritis in rats, and it is suggested that AC is recommended to alleviate the arthritis-related symptoms in humans.     

Cytoprotective effect of Scutellaria baicalensis in CA1 hippocampal neurons of rats after global cerebral ischemia

Based on the use of Scutellaria baicalensis for the treatment of stroke in traditional Oriental medicine, the current study was carried out to evaluate neuroprotective effects of S. baicalensis after transient global ischemia using rat 4-vessel occlusion model. Methanol extracts from the dried roots of S. baicalensis (0.1-10 mg/kg) administered intra-peritoneally significantly protected CA1 neurons against 10 min transient forebrain ischemia as demonstrated by measuring the density of neuronal cells stained with Cresyl violet. Methanol extract of S. baicalensis inhibited microglial tumor necrosis factor-alpha (TNF-alpha) and nitric oxide production, and protected PC12 cells from hydrogen peroxide-induced toxicity in vitro.     

Somatic afferent fibers which continuously discharge after being isolated from their receptors.

A previous study in our laboratory has shown that some afferent axons produce prolonged discharges after the axons have been completely isolated. We have attempted to identify the type of afferent fibers displaying such activity. Single unit activity was recorded from a filament dissected from the distal stump of the cut sural or plantar nerve of an anesthetized rat. After thorough identification of the receptor type, the nerve was cut at a site between the recording electrode and the receptive field, completely isolating the fiber being recorded. Unit activity was recorded up to 1 h after sectioning the nerve. Upon sectioning the nerve, most units showed brief injury discharges lasting only a few seconds. However, 21 of 70 units exhibited prolonged discharges lasting at least 30 min after having been isolated from their receptors. These 21 units included 8 slowly adapting type II cutaneous mechanoreceptors, 3 Pacinian corpuscles and 10 muscle spindle afferent units. These results suggest that prolonged injury discharges can be produced in the axons of the slowly adapting type II cutaneous mechanoreceptors, Pacinian corpuscles, and muscle spindle afferents. This phenomenon may have important clinical and experimental consequences.