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Long-term potentiation in an isolated peripheral nerve-spinal cord preparation.

1. Long-lasting increases in synaptic efficacy following repetitive stimulation have been demonstrated at several sites in the CNS, where they are collectively termed long-term potentiation (LTP). LTP is of interest with respect to its presumptive relationship to learning and memory in hippocampus. In the spinal cord in vivo, an LTP-like phenomenon is thought to underlie the allodynia and hyperalgesia that follows some peripheral injuries. 2. We investigated the capacity of the isolated neonatal rat spinal cord to sustain a long-lasting increase in a nociceptive-related slow ventral root potential (sVRP) recorded from a lumbar root after a tetanic train of stimuli to the peripheral cutaneous saphenous nerve. Stimuli were delivered at a low constant (0.02 s-1) frequency during a 30-min control period. A tetanic stimulus train (10 s-1 for 60 s) was then given followed by a resumption of low (0.02 s-1) frequency stimulation. Potentiation was defined as an increase in sVRP area > 2 SD above control mean. 3. Twenty of 20 preparations showed immediate posttetanic potentiation. In 13 of the 20, potentiation was maintained for > or = 1 h after the tetanic stimulus train. 4. Potentiation was dependent on activation of C fibers during the inducing train; stimuli below C-fiber threshold, activating only A fibers, were ineffective. Potentiation was selectively expressed by a long-latency component of the sVRP elicited by stimuli at a strength that evoked both A- and C-fiber responses in the nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Opposing effects of spinal nerve ligation on calcium-activated potassium currents in axotomized and adjacent mammalian primary afferent neurons.

UNLABELLED: Calcium-activated potassium channels regulate AHP and excitability in neurons. Since we have previously shown that axotomy decreases I(Ca) in DRG neurons, we investigated the association between I(Ca) and K((Ca)) currents in control medium-sized (30-39 microM) neurons, as well as axotomized L5 or adjacent L4 DRG neurons from hyperalgesic rats following L5 SNL. Currents in response to AP waveform voltage commands were recorded first in Tyrode's solution and sequentially after: 1) blocking Na(+) current with NMDG and TTX; 2) addition of K((Ca)) blockers with a combination of apamin 1 microM, iberiotoxin 200 nM, and clotrimazole 500 nM; 3) blocking remaining K(+) current with the addition of 4-AP, TEA-Cl, and glibenclamide; and 4) blocking I(Ca) with cadmium. In separate experiments, currents were evoked (HP -60 mV, 200 ms square command pulses from -100 to +50 mV) while ensuring high levels of activation of I(K(Ca)) by clamping cytosolic Ca(2+) concentration with pipette solution in which Ca(2+) was buffered to 1 microM. This revealed I(K(Ca)) with components sensitive to apamin, clotrimazole and iberiotoxin. SNL decreases total I(K(Ca)) in axotomized (L5) neurons, but increases total I(K(Ca)) in adjacent (L4) DRG neurons. All I(K(Ca)) subtypes are decreased by axotomy, but iberiotoxin-sensitive and clotrimazole-sensitive current densities are increased in adjacent L4 neurons after SNL. In an additional set of experiments we found that small-sized control DRG neurons also expressed iberiotoxin-sensitive currents, which are reduced in both axotomized (L5) and adjacent (L4) neurons. CONCLUSIONS: Axotomy decreases I(K(Ca)) due to a direct effect on K((Ca)) channels. Axotomy-induced loss of I(Ca) may further potentiate current reduction. This reduction in I(K(Ca)) may contribute to elevated excitability after axotomy. Adjacent neurons (L4 after SNL) exhibit increased I(K(Ca)) current.

Animals↗

Bilateral sacral spinal nerve stimulation for fecal incontinence after low anterior rectum resection.

BACKGROUND AND AIMS: The somatomotor innervation pattern has been shown to differ in patients undergoing percutaneous nerve evaluation for sacral nerve stimulation. In some patients bilateral stimulation might improve clinical outcome; however, only single-channel pulse generators have until now been available. We report a patient with fecal incontinence after surgery for rectal carcinoma in whom a dual-channel, individually programmable, pulse generator permitted implantation of neurostimulation electrodes bilaterally. PATIENTS AND METHODS: Intractable fecal incontinence developed in a 48-year-old man who underwent low anterior rectum resection, owing mainly to reduced internal anal sphincter function. The morphology of the anal sphincter was without defect. Based on the findings of unilateral and bilateral temporary sacral nerve stimulation the patient underwent placement of foramen electrodes on S4 bilaterally. Both electrodes were connected to a dual-channel impulse generator for permanent low-frequency stimulation. RESULTS: The percentage of incontinent bowel movements decreased during unilateral test stimulation from 37% to 11%, during bilateral test stimulation to 4%, and with chronic bilateral stimulation to 0%. The Wexner continence score improved from 17 preoperatively to 2, and quality of life (ASCRS score) was notably enhanced. Anorectal manometry revealed improved striated anal sphincter function; the internal anal sphincter remained unaffected. CONCLUSION: Sacral nerve stimulation can effectively treat incontinence after rectal resection, and bilateral stimulation can improve the therapeutic effect.

Electric Stimulation Therapy↗

Sacral spinal nerve stimulation for faecal incontinence: multicentre study.

BACKGROUND: In patients with faecal incontinence in whom conservative treatment fails, options are limited for those with a functionally deficient but morphologically intact sphincter. We investigated the effect of sacral nerve stimulation on continence and quality of life. METHODS: In this multicentre prospective trial, 37 patients underwent a test stimulation period, followed by implantation of a neurostimulator for chronic stimulation in 34. Effect on continence was assessed by daily bowel-habit diaries over a 3-week period and on quality of life by the disease-specific American Society of Colon and Rectal Surgeons (ASCRS) questionnaire and the standard short form health survey questionnaire (SF-36). Every patient served as his or her own control. FINDINGS: Frequency of incontinent episodes per week fell (mean 16.4 vs 3.1 and 2.0 at 12 and 24 months; p<0.0001) for both urge and passive incontinence during median follow-up of 23.9 months. Mean number of days per week with incontinent episodes also declined (4.5 vs 1.4 and 1.2 at 12 and 24 months, p<0.0001), as did staining (5.6 vs 2.4 at 12 months; p<0.0001) and pad use (5.9 vs 3.7 at 12 months; p<0.0001). Ability to postpone defecation was enhanced (at 12 months, p<0.0001), and ability to completely empty the bowel was slightly raised during follow-up (at 12 months, p=0.4122). Quality of life improved in all four ASCRS scales (p<0.0001) and in seven of eight SF-36 scales, though only social functioning was significantly improved (p=0.0002). INTERPRETATION: Sacral nerve stimulation greatly improves continence and quality of life in selected patients with morphologically intact or repaired sphincter complex offering a treatment for patients in whom treatment options are limited.

Adult↗

Effects of acute, graded compression on spinal nerve root function and structure. An experimental study of the pig cauda equina.

A well-controlled experimental model for analysis of compression-induced functional changes of the porcine cauda equina is presented. The model allows for electrophysiologic investigation of a variety of neurophysiologic changes induced by nerve root deformation. At an acute pressure threshold of 50-75 mm Hg, changes in both afferent and efferent conduction are induced. With higher compression pressure, a differential recovery in afferent and efferent conduction is seen.

Action Potentials↗

Cultured, autologous nucleus pulposus cells induce functional changes in spinal nerve roots.

STUDY DESIGN: Nerve conduction velocity in pig nerve roots was assessed after application of various preparations of nucleus pulposus and control. OBJECTIVE: To study whether cultured nucleus pulposus cells could reduce nerve conduction velocity after epidural application. SUMMARY OF BACKGROUND DATA: It is known that nucleus pulposus applied epidurally may reduce the nerve conduction velocity of the adjacent nerve roots and that this reduction seems to be related to the cells of the nucleus pulposus. METHODS: Nucleus pulposus cells and fibroblasts were cultured for 3 weeks, and various preparations were applied to the cauda equina in 29 pigs. The cells were always from the same animals from which they had been harvested. After 1 week, nerve conduction velocity was determined by local electrical stimulation. RESULTS: Application of live fibroblasts and conditioned culture medium from the nucleus pulposus cell culture dishes did not induce significant reduction of conduction velocity, compared with application of dead fibroblasts, which served as control. However, application of live and dead nucleus pulposus cells induced significant reductions. CONCLUSIONS: Application of nucleus pulposus cells reproduced the previously seen reduction in nerve conduction velocity induced by nonmodified nucleus pulposus. Because membranes of the nucleus pulposus cells had similar effects, it can be assumed that the effects are related to membrane-bound substances or structures.

Animals↗