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PubMed1987

Exocrine pancreatic function in dogs with denervated pancreas.

There is strong evidence that the vagus nerve plays an important role in exocrine pancreatic secretion. In the present study we examined the effect of total extrinsic denervation of the pancreas on exocrine pancreatic secretion to different stimuli in dogs. In the experiments we used the model of the orthotopic autotransplanted dog pancreas as described by Debas et al. Denervation of the gland did not significantly alter water and bicarbonate response to secretin. The dose-response curve of caerulein showed the denervated pancreas as sensitive as the intact gland. However, autotransplantation of the pancreas caused a significant decrease (p less than 0.05) in protein secretion during intraintestinal L-tryptophan in increasing doses. Furthermore, bicarbonate and protein secretion after food intake was significantly decreased in the denervated pancreas (protein: peak levels 380 mg/15 min and 135 mg/15 min; bicarbonate: 3.2 mEq/15 min and 1.4 mEq/15 min) (p less than 0.02). From our data we conclude that the denervated pancreas is as sensitive as the intact pancreas to stimulation by exogenous secretin and caerulein, whereas denervation of the pancreas causes an important influence in the intestinal phase of pancreatic secretion.

Animals↗
PubMedDate not supplied

Radiofrequency denervation of lumbar facet joints in the treatment of chronic low back pain: a randomized, double-blind, sham lesion-controlled trial.

OBJECTIVES: Radiofrequency facet joint denervation procedures have been common practice for 2 decades in treatment of chronic low back pain. We designed this multicenter, randomized, double-blind, sham treatment controlled trial to determine the efficacy of radiofrequency facet joint denervation, as it is routinely performed. METHODS: Inclusion criteria were low back pain, duration more than 6 months, and >or=50% Visual Analog Scale (VAS) reduction on diagnostic block. Exclusion criteria were prior radiofrequency treatment, radicular syndrome, coagulopathies, specific allergies, cancer, and pregnancy. A total of 81 out of 462 patients were randomized to undergo radiofrequency facet joint denervation or sham treatment. The first evaluation was carried out 3 months after treatment. Primary outcome was determined with a combined outcome measure comprising VAS, physical activities, and analgesic intake, from a twice-weekly recorded diary. Secondary outcome measures were the separate diary parameters, global perceived effect (complete relief, >50% relief, no effect, pain increase), and SF-36 Quality of Life Questionnaire. RESULTS: There were no dropouts before the first evaluation. The combined outcome measure showed no differences between radio- frequency facet joint denervation (n=40; success 27.5%) and sham (n=41; success 29.3%) (P=0.86). The VAS in both groups improved (P<0.001). Global perceived effect improved after radiofrequency facet joint denervation (P<0.05). The other secondary outcome parameters showed no significant differences. Relevant costs were evaluated. DISCUSSION: The combined outcome measure and VAS showed no difference between radiofrequency and sham, though in both groups, significant VAS improvement occurred. The global perceived effect was in favor of radiofrequency. In selected patients, radiofrequency facet joint denervation appears to be more effective than sham treatment.

Adolescent↗
PubMed2004

Complications of lumbar facet radiofrequency denervation.

STUDY DESIGN: Retrospective. OBJECTIVE: To assess the incidence of complications associated with fluoroscopically guided percutaneous radiofrequency denervation of the lumbar facet joints. SUMMARY OF BACKGROUND DATA: Based on the results of previous efficacy studies, complications associated with facet joint radiofrequency denervation procedures appear to be rare. No formal safety assessment for this procedure has been performed to date. METHODS: We conducted retrospective chart reviews to identify complications that occurred within 8 weeks of facet joint radiofrequency denervation procedures performed at the Mayo Clinic in Jacksonville during a 5-year period. Only procedures that included radiofrequency electrode placement between the L1 transverse process and the sacral ala were included. The chart of each patient was reviewed and adjudicated by a panel of 4 physicians before being classified as a complication. RESULTS: Ninety-two patients received a total of 616 radiofrequency lesions during 116 separate denervation procedures. An average of 5 +/- 3 lesions were performed during each radiofrequency denervation procedure. Six minor complications were identified, yielding a 1.0% overall incidence of minor complications per radiofrequency site. Complications included: 3 cases of localized pain lasting more than 2 weeks (0.5%) and 3 cases of neuritic pain lasting less than 2 weeks (0.5%). No cases of infection, new motor deficits, or new sensory deficits were identified. CONCLUSIONS: Fluoroscopically guided percutaneous radiofrequency denervation of the lumbar facets is associated with an overall 1.0% incidence of minor complications per lesion site.

Aged↗
PubMed1979

Local development of action potentials in slow muscle fibres after complete or partial denervation.

Pyriformis muscles of Rana temporaria were completely or partially denervated by cutting the sciatic nerve or some of the small nerve branches entering the muscle. One stimulating and one to three recording microelectrodes were inserted along the fibres in order to compare the electrical activity at these points. In an early period following denervation action potentials of variable size and shape could be observed; these action potentials were often composed of two, sometimes of three or four, components. The size of individual components depended on the position of the recording microelectrode. Individual components could occasionally be triggered separately by adjusting the strength of the stimulating current pulse; propagation of these "all or none" responses was absent. In other fibres one component of the action potential could trigger another one several millimetres apart, thus indicating propagation. Conduction velocities were approximately 0.4 m/s. In partially denervated slow fibres, endplate potentials were confined to one lateral segment of the fibres, while the action potential occupied the denervated part of the membrane. The amplitudes of endplate and action potentials varied inversely with distance. Rough estimates of the length constant of the slow fibre membrane were calculated from the spatial decay of action potentials, endplate potentials and hyperpolarizing electrotonic potentials; mean values obtained were 2.5, 4.8 and 7.7 mm respectively. The results suggest that following denervation Na channels are built into discrete areas of the slow fibre membrane and that this process depends on the amount of denervation in individual fibres.

Action Potentials↗
PubMed1988

Expression of ACh-activated channels and sodium channels by messenger RNAs from innervated and denervated muscle.

Xenopus oocytes were used to express polyadenylated messenger RNAs (mRNAs) encoding acetylcholine receptors and voltage-activated sodium channels from innervated and denervated skeletal muscles of cat and rat. Oocytes injected with mRNA from denervated muscle acquired high sensitivity to acetylcholine, whereas those injected with mRNA from innervated muscle showed virtually no response. Hence the amount of translationally active mRNA encoding acetylcholine receptors appears to be very low in normally innervated muscle, but increases greatly after denervation. Conversely, voltage-activated sodium currents induced by mRNA from innervated muscle were about three times larger than those from denervated muscle; this result suggests that innervated muscle contains more mRNA coding for sodium channels. The sodium current induced by mRNA from denervated muscle was relatively more resistant to block by tetrodotoxin. Thus a proportion of the sodium channels in denervated muscle may be encoded by mRNAs different from those encoding the normal channels.

Acetylcholine↗
PubMed1976

Persistence of junctional acetylcholine receptors following denervation.

The relative number of acetylcholine receptors at normal and denervated end plates in rat soleus muscles was studied using the binding of 125I-alpha-bungarotoxin as a quantitative assay. After short-term denervation (up to 2.4 weeks), the extrajunctional binding increased, but there was no change in specific binding to the motor end plate. Denervation for longer periods (up to 7 weeks) reduced binding sites at the end plate by as much as 60-70%. Direct electrical stimulation of these muscles for the entire period of denervation did not prevent the slow loss of junctional binding sites, even though it was adequate to abolish the increase in extrajunctional binding. Cross-innervation by a foreign nerve at a site distant from the original end plates was more effective than stimulation in preserving the old end plates; in cross-innervated muscles, many denervated end plates continued to bind normal amounts of toxin for over 4 months. In comparison with the rapid rate of appearance or disappearance of extrajunctional ACh receptors, however, the number of junctional receptors at all denervated end plates was quite stable, suggesting that the persistence of these receptors is not immediately dependent on the presence of a motor nerve terminal.

Acetylcholine↗
PubMed2001

Small-conductance calcium-activated potassium currents in mouse hyperexcitable denervated skeletal muscle.

1. Hyperexcitability in denervated skeletal muscle is associated with the expression of SK3, a small-conductance Ca2+-activated K+ channel (SK channel). SK currents were examined in dissociated fibres from flexor digitorum brevis (FDB) muscle using the whole-cell patch clamp configuration. 2. Depolarization activated a K+-selective, apamin-sensitive and iberiotoxin-insensitive current, detected as a tail current upon repolarization, in fibres from denervated but not innervated muscle. Dialysis of the fibres with 20 mM EGTA in the patch pipette solution eliminated the tail current, consistent with this current reflecting Ca2+-activated SK channels expressed only in denervated muscle. 3. Activation of SK tail currents depended on the duration of the depolarizing pulse, consistent with a rise in intracellular Ca2+ due to release from the sarcoplasmic reticulum (SR) and influx through voltage-gated Ca2+ channels. 4. The envelope of SK tail currents was diminished by 10 microM ryanodine for all pulse durations, whereas 2 mM cobalt reduced the SK tail current for pulses greater than 80 ms, demonstrating that Ca2+ release from the SR during short pulses primarily activated SK channels. 5. In current clamp mode with the resting membrane potential set at -70 mV, denervation decreased the action potential threshold by approximately 8 mV. Application of apamin increased the action potential threshold in denervated fibres to that measured in innervated fibres, suggesting that SK channel activity modulates the apparent action potential threshold. 6. These results are consistent with a model in which SK channel activity in the T-tubules of denervated skeletal muscle causes a local increase in K+ concentration that results in hyperexcitability.

Action Potentials↗
PubMed1983

Effect of denervation and reinnervation on oxidation of [6-14C]glucose by rat skeletal muscle homogenates.

We studied the effects of denervation and reinnervation of the rat extensor digitorum longus muscle (EDL) on the oxidation of [6-14C]glucose to 14CO2. The rate of 14CO2 production decreased dramatically following denervation, and the decrease became significant 20 days after nerve section. Prior to day 20, changes apparently reflected the decline of muscle mass. Decreased 14CO2 production was due to reduced capacity of the enzymatic system (apparent Vmax); there was no change in apparent affinity for glucose (apparent Km). Mixing experiments revealed that the loss of oxidative capacity following denervation is not caused by production of soluble inhibitors by degenerating muscle. Oxidative metabolism, as measured by 14CO2 evolution, recovered during reinnervation. Surprisingly, the specific activity in reinnervated muscles displayed an "overshoot" of approximately 50%, which returned to control by day 60, possibly reflecting increased energy demand by the growing muscle. The time-course of the denervation-mediated change indicates that altered oxidative capacity is secondary to events that initiate denervation changes in muscle. Nevertheless, diminished oxidative capacity may be of considerable metabolic significance in denervated muscle.

Animals↗
PubMed1984

Increased cytosolic androgen receptor binding in rat striated muscle following denervation and disuse.

We investigated the effects of denervation and disuse on cytosolic androgen receptor binding by rat striated muscle. Denervation of the extensor digitorum longus and tibialis anterior muscles caused a 40-50% increase in cytosolic androgen receptor concentration with no change in apparent binding affinity. This effect was evident at 6 h postdenervation, maximal at 24 h, and declined to 120% of the control level 72 h after denervation. A 40% increase in cytosolic androgen receptor concentration was also noted 24 hr after denervation of the hormone-sensitive levator ani muscle. The effect of denervation on androgen receptors was not blocked by in vivo injection of cycloheximide; therefore, de novo receptor synthesis probably is not involved in the observed increase. Disuse, produced by subperineurial injection of tetrodotoxin into the tibial and common peroneal branches of the sciatic nerve, mimicked the effect of denervation on androgen receptor binding, suggesting that neuromuscular activity is important in regulation of receptor concentration. Possible mechanisms subserving this effect are discussed.

Animals↗
PubMed1991

A role for acetylcholine-nicotinic receptor interactions in the selective increase of rat skeletal muscle G4 acetylcholinesterase following short-term denervation.

The present work addresses the effects of short-term denervation on acetylcholinesterase (AChE; EC 3.1.1.7) isoenzymes in anterior gracilis muscles from adult male Sprague-Dawley rats. It examines possible relationships between AChE isoform changes and other denervation phenomena, and evaluates the importance of acetylcholine (ACh)-nicotinic receptor interactions in selectively modulating the activity of G4 AChE. Results confirm that denervation causes a specific, transient increase in G4 AChE and show that: most of the increment can be explained by the hydrophobic species of this isoenzyme; changes in AChE isoforms markedly precede the onset of spontaneous electromechanical activity (fibrillation), as well as acetylcholine receptor (AChR) proliferation; and the G4 AChE response is eliminated when AChRs are blocked by alpha-bungarotoxin treatment performed before but not after (24 h) denervation. These data point to the absence of direct causal relationships between the G4 AChE increment and fibrillation, AChR proliferation, or changes in the release of this isoform from denervated muscle. In turn, they suggest the participation of AChR activation in triggering the G4 AChE response and emphasize the possible role of ACh-AChR interactions in modulating the production of this isoenzyme in not only denervated but also innervated fast-twitch muscles.

Acetylcholine↗
PubMed2005

Muscle fiber regeneration in human permanent lower motoneuron denervation: relevance to safety and effectiveness of FES-training, which induces muscle recovery in SCI subjects.

Morphologic characteristics of the long-term denervated muscle in animals suggest that some original fibers are lost and some of those seen are the result of repeated cycles of fiber regeneration. Muscle biopsies from lower motoneuron denervated patients enrolled in the EU Project RISE show the characteristics of long-term denervation. They present a few atrophic or severely atrophic myofibers dispersed among adipocytes and connective tissue (denervated degenerated muscle, DDM). Monoclonal antibody for embryonic myosin shows that regenerative events are present from 1- to 37-years postspinal cord injury (SCI). After 2- to 10-years FES-training the muscle cryosections present mainly large round myofibers. In the FES-trained muscles the regenerative events are present, but at a lower rate than long-term denervated muscles (myofiber per mm2 of cryosection area: 0.8 +/- 1.3 in FES vs. 2.3 +/- 2.3 in DDM, mean +/- SD, P = 0.011). In our opinion this is a sound additional evidence of effectiveness of the Kern's electrical stimulation protocol for FES of DDM. In any case, the overall results demonstrate that the FES-training is safe: at least it does not induce more myofiber damage/regeneration than denervation per se.

Electric Stimulation↗
PubMed2005

Electrical stimulation of denervated muscles: first results of a clinical study.

To evaluate the effects of electrical stimulation on denervated muscles in spinal cord injured humans, the EU Project RISE was started in 2001. The aims of this project are: to design and build sufficient stimulators; to develop stimulation protocols by means of mathematical models, animal experiments, and practice in humans with denervated lower limbs; to develop examination methods and devices for evaluation of electrical stimulation training effects; and to acquire basic scientific knowledge on denervated and stimulated denervated muscle. In the clinical study 27 spinal cord injured individuals were included, furthermore 13 pilot patients participated. After a series of initial examinations they underwent an electrical stimulation program for their denervated lower limb muscles. Some of the patients have already follow up examinations. A marked increase of muscle mass and quality was observed, the trophic situation of the denervated lower limbs had improved obviously.

Adult↗
PubMed1987

Effects of chronic stimulation on the size and speed of long-term denervated and innervated rat fast and slow skeletal muscles.

This study seeks to identify the mechanisms which motoneurones use to control the contractile force and speed of skeletal muscles. We have stimulated directly slow soleus (SOL) and fast extensor digitorum longus (EDL) muscles of adult rats intermittently at 100 Hz for 1-9 months. The muscles were either chronically denervated, denervated and reinnervated, or normally innervated. The stimulation started either immediately, or more commonly, after 1-9 months of denervation. Stimulation starting several months after denervation increased the mean maximum tetanic tension 37 times in SOL and eight times in EDL. These values represented 40 and 12% of the increases obtained by reinnervation after comparable periods of time. In denervated SOL and EDL muscles stimulated directly for more than 2 months, the mean isometric twitch contraction times were 13 and 12.7 ms, as in normal EDL muscles (13 ms). In innervated SOL muscles stimulated directly for 1-4 months, the mean twitch contraction times were 23.6 ms (normally innervated) and 19.2 ms (reinnervated), which were considerably shorter than in normal control SOL muscles (39.2 ms). Single motor unit recordings revealed that the natural (background) nerve impulse activity was essentially unaffected by the stimulation. Twitch contraction time and percentage of type II fibres in SOL muscles were related. The fastest muscles (denervated and stimulated) consisted of 100% type II fibres (with one exception), the second fastest (reinnervated and stimulated) of 70-50%, the third fastest (normally innervated and stimulated) of 45-0%, the second slowest (reinnervated) of 15-0%, and the slowest muscles (innervated controls) of 5-0% type II fibres.

Animals↗
PubMed2006

Time course of changes in angiogenesis-related factors in denervated muscle.

AIM: Denervation leads to capillary regression in skeletal muscle. To gain insight into the regulation of this process, we investigated the time course of changes in capillary supply and gene expression of angiogenesis-related factors during muscle denervation. METHOD: Female mice underwent surgery to transect the sciatic nerve, and then the gastrocnemius muscles were isolated at 12 h, 1, 3, 5, 10, 20, or 30 days after surgery. The capillary supply was assessed by immunohistochemistry using anti-PECAM-1/CD31 antibody. The mRNA levels for angiogenesis-related factors were analysed using a real-time polymerase chain reaction. RESULTS: We found that the capillary-to-fibre ratio began to decrease 10 days after muscle denervation and decreased by 52% after 30 days. The levels of mRNA for vascular endothelial growth factor (VEGF), its receptors [fms-like tyrosine kinase (Flt-1) and a kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/Flk-1)], angiopoietin-1 and angiopoietin-2 of denervated muscle were immediately down-regulated after 12 h and remained lower than control muscle until 30 days after muscle denervation. The levels of mRNA for the VEGF receptor, neuropilin-1, angiopoietin receptor and Tie-2 decreased within 12-24 h, but returned to near those of control muscle after 10-20 days, and again decreased after 30 days. CONCLUSIONS: These findings suggest that denervation-induced capillary regression may be associated with down-regulation of VEGF and angiopoietin signalling.

Angiogenesis Inducing Agents↗
PubMed2002

The expression profile of myogenic transcription factors in satellite cells from denervated rat muscle.

The muscle-specific transcription factors of the MyoD family are altered after denervation. In order to determine whether this shift takes place in satellite cells (SC), we investigated the expression pattern of MyoD, myf5, myogenin, and MRF4 in SC. Hindlimb muscles of rats were denervated for 2 days to 4 weeks. SC were isolated, pooled and the transcription of all 4 factors was assessed by RT-PCR. Protein expression was assessed in histological sections of soleus and anterior tibial (TA) muscles; SC were identified by M-cadherin. Pooled SC from innervated muscles expressed myf5 mRNA, and very weakly MyoD and myogenin mRNA. MyoD and myogenin protein was found in only few SC. After denervation, pooled SC expressed myf5 mRNA, and very weakly myogenin and MRF4 mRNA. Myogenin protein was found in less than about 10% of the cells, whereas MRF4 protein was absent from SC. We conclude that the presence of myf5 and the absence of MyoD and MRF4 protein in SC after denervation indicated the quiescent state of the cell cycle. A subset of SC has additionally acquired myogenin. SC after denervation might be less easily recruited into the mitotic cycle than SC from normal muscle, rendering regeneration of denervated muscle less efficient than normal muscle.

Animals↗
PubMed1995

Ca2+ release channels in rat denervated skeletal muscles.

Sarcoplasmic reticulum (SR) Ca2+ release channel-ryanodine receptors (RYR1) from rat fast-twitch skeletal muscle were studied by incorporating heavy sarcoplasmic reticulum membranes into a lipid bilayer. Channels from normal and denervated muscles had the same conductance as that reported for rabbits (about 500 pS) in 250:250 mM cis:trans caesium methanesulphonate. Caffeine (0.1 mM) induced a larger increase in the open probability (Po) in denervated than in normal channels. The caffeine effect was caused by changes in mean open and burst time distributions. Longer opening and burst events were detected in the presence of caffeine. High caffeine concentrations (4 mM) gave similar results in channels from normal and denervated muscles. In denervated muscle, unlike intact muscle, the Ca2+ release channel was not activated at millimolar Ca2+ concentrations; this is similar to the cardiac isoform of the channel. Maximal channel activation was shifted to higher Ca2+ concentrations (pCa 4) and the channel remained activated at millimolar Ca2+ concentrations. The main effect of millimolar Ca2+ concentrations upon Ca2+ release channels from denervated muscles was an increase in the mean open time, with a concomitant increment of the mean burst duration. Alterations in channel gating properties in calcium and caffeine account for changes in the mechanical response after skeletal muscle denervation.

Animals↗
PubMed1968

Sodium movements in denervated muscle and the effects of antimycin A.

1. Fibre sodium in rat diaphragm exchanged at a faster rate in muscles which had been denervated 8 days previously. The half-time was 3.7 min for outward movement in denervated muscles and 5.1 min in controls.2. The inward movement of sodium was also faster in denervated muscle as compared with controls, and the calculated permeability to sodium was approximately doubled.3. In the presence of antimycin A (1.8 x 10(-5)M), the outward movement of sodium in denervated diaphragm was slowed and the fibres gained sodium and lost potassium.4. Antimycin markedly reduced the twitch produced by stimulation of denervated diaphragm, and also the response to acetylcholine. Similar effects were found in denervated tibialis anterior of the cat.

Acetylcholine↗
PubMed1972

Neurotrophic regulation of muscle cholinesterase: effects of botulinum toxin and denervation.

1. In order to determine the role of acetylcholine (ACh) transmission in neurotrophic regulation of muscle cholinesterase (ChE), the effects of botulinum toxin treatment were compared with those of denervation, in terms of two fractions of muscle ChE. The sternocleidomastoid muscles of rats were either denervated or injected with botulinum toxin. After 7 days the muscles were frozen, and sequential sections were assayed for acetylcholinesterase activity. By this method, the ChE activity of end-plates (EPChE) and non-end-plate regions (background ChE, BChE) were separately determined.2. The background ChE was reduced to the same extent by botulinum toxin and denervation. This is interpreted to mean that the neurotrophic regulation of BChE may be wholly cholinergic.3. The EPChE was significantly reduced by both treatments, but the effect of botulinum toxin was only half as great as that of denervation. This indicates that EPChE is only partially regulated by ACh transmission. The larger effect of denervation suggests that some non-cholinergic influence may be operating in this situation as well. Disruption of the structural integrity of the end-plate, with consequent loss of binding sites for the ChE, may account for the additional effect of denervation.

Acetylcholine↗