Chronic Sciatic Neuropathy in Rat Reduces Voluntary Wheel-Running Activity With Concurrent Chronic Mechanical Allodynia.

BACKGROUND: Animal models of peripheral neuropathy produced by a number of manipulations are assessed for the presence of pathologic pain states such as allodynia. Although stimulus-induced behavioral assays are frequently used and important to examine allodynia (ie, sensitivity to light mechanical touch; von Frey fiber test), other measures of behavior that reflect overall function are not only complementary to stimulus-induced responsive measures, but are also critical to gain a complete understanding of the effects of the pain model on quality of life, a clinically relevant aspect of pain on general function. Voluntary wheel-running activity in rodent models of inflammatory and muscle pain is emerging as a reliable index of general function that extends beyond stimulus-induced behavioral assays. Clinically, reports of increased pain intensity occur at night, a period typically characterized with reduced activity during the diurnal cycle. We therefore examined in rats whether alterations in wheel-running activity were more robust during the inactive phase compared with the active phase of their diurnal cycle in a widely used rodent model of chronic peripheral neuropathic pain, the sciatic nerve chronic constriction injury (CCI) model. METHODS: In adult male Sprague Dawley rats, baseline (BL) hindpaw threshold responses to light mechanical touch were assessed using the von Frey test before measuring BL activity levels using freely accessible running wheels (1 hour/day for 7 sequential days) to quantify the distance traveled. Running wheel activity BL values are expressed as total distance traveled (m). The overall experimental design was after BL measures, rats underwent either sham or CCI surgery followed by repeated behavioral reassessment of hindpaw thresholds and wheel-running activity levels for up to 18 days after surgery. Specifically, separate groups of rats were assessed for wheel-running activity levels (1 hour total/trial) during the onset (within first 2 hours) of either the (1) inactive (n = 8/group) or (2) active (n = 8/group) phase of the diurnal cycle. An additional group of CCI-treated rats (n = 8/group) was exposed to a locked running wheel to control for the potential effects of wheel-running exercise on allodynia. The 1-hour running wheel trial period was further examined at discrete 20-minute intervals to identify possible pattern differences in activity during the first, middle, and last portions of the 1-hour trial. The effect of neuropathy on activity levels was assessed by measuring the change from their respective BLs to distance traveled in the running wheels. RESULTS: Although wheel-running distances between groups were not different at BL from rats examined during either the inactive phase of the diurnal cycle or active phase of the diurnal cycle, sciatic nerve CCI reduced running wheel activity levels compared with sham-operated controls during the inactive phase. In addition, compared with sham controls, bilateral low-threshold mechanical allodynia was observed at all time points after surgical induction of neuropathy in rats with free-wheel and locked-wheel access. Allodynia in CCI compared with shams was replicated in rats whose running wheel activity was examined during the active phase of the diurnal cycle. Conversely, no significant reduction in wheel-running activity was observed in CCI-treated rats compared with sham controls at any time point when activity levels were examined during the active diurnal phase. Finally, running wheel activity patterns within the 1-hour trial period during the inactive phase of the diurnal cycle were relatively consistent throughout each 20-minute phase. CONCLUSIONS: Compared with nonneuropathic sham controls, a profound and stable reduction of running wheel activity was observed in CCI rats during the inactive phase of the diurnal cycle. A concurrent robust allodynia persisted in all rats regardless of when wheel-running activity was examined or whether they ran on wheels, suggesting that acute wheel-running activity does not alter chronic low-intensity mechanical allodynia as measured using the von Frey fiber test. Overall, these data support that acute wheel-running exercise with limited repeated exposures does not itself alter allodynia and offers a behavioral assay complementary to stimulus-induced measures of neuropathic pain.

Introduction of new safety technologies into central venous access.

The American Society of Anesthesiologists, the Anesthesia Patient Safety Foundation, the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO), and the Patient Safety and Quality Improvement Act of 2005 encourage anesthesiology departments to institute systematic improvements in patient safety, including but not limited to integration of new safety technologies. The evaluation and method of use of the reciprocating procedure device in central venous access is presented.

Kavain attenuates vascular contractility through inhibition of calcium channels.

Kavain is a biologically active compound from the Oceanic plant Piper methysticum (kava). Traditional medicinal uses of the kava root are many. Kava is increasingly being utilized by Western societies for its anxiolytic effects. Recent reports indicate that kavain blocks ion channels in neural tissue, relaxes precontracted ileum, and relaxes precontracted airway. Thus, we investigated the potential ability of this plant-derived compound to alter vascular smooth muscle function. Thoracic aortae were isolated from Sprague-Dawley rat and cut into 4 mm rings. Rings were placed in tissue baths and suspended from force-displacement transducers for the measurement of isometric tension. In a dose-dependent manner, kavain (10(-6) M to 10(-3) M) was found to relax aortic rings precontracted with phenylephrine (PE). This response was not dependent on functional endothelium. In addition, kavain pretreatment (3 x 10(-5) M or 3 x 10(-4) M) attenuated vascular smooth muscle contraction evoked by PE. However, kavain failed to attenuate PE-mediated contraction in calcium (Ca(++))-free buffer, indicating that intracellular signaling processes were likely not affected. Also, kavain did attenuate the contraction elicited by administration of Ca(++) to depolarized tissue. Interestingly, in rings pre-treated with the selective L-type Ca(++) channel blocker nifedipine, kavain-mediated relaxation was inhibited. Lastly, in rings selectively contracted with an L-type calcium channel activator, kavain elicited dose-dependent (and ultimately complete) relaxation. These data strongly suggest that kavain impairs vascular smooth muscle contraction, likely through inhibition of Ca(++) channels.