denervation

The loss of nerve supply can be caused by injury, disorders, or result from a surgical procedure.

Denervation can occur as a consequence of nerve injury. The three primary categories of nerve injury are neurapraxia, axonotmesis, and neurotmesis, each corresponding to varying degrees of damage and potential for recovery. In cases of nerve injury, the brain demonstrates an impressive ability to rewire or reorganize its neuronal circuitry. This plasticity enables the brain to compensate for the disruptions in neuronal communication that result from the injury.{{Cite journal|last1 = Cotman|first1 = Carl W.|last2 = Berchtold|first2 = Nicole C.|date = 1998-01-01|title = Plasticity and growth factors in injury response|url = http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1098-2779(1998)4:33.0.CO;2-X/abstract|journal = Mental Retardation and Developmental Disabilities Research Reviews|language = en|volume = 4|issue = 3|pages = 223–230|doi = 10.1002/(sici)1098-2779(1998)4:3<223::aid-mrdd10>3.0.co;2-x|issn = 1098-2779|url-access = subscription}}

Denervation processes are strongly associated with the symptoms experienced in post-polio syndrome. Individuals with post-polio syndrome undergo a continuous cycle of denervation and reinnervation that occurs after acute poliomyelitis. Over time, this cycle leads to an increase in the size of motor units in skeletal muscle fibers. Eventually, the motor unit areas grow to a point where reinnervation is no longer possible, resulting in uncompensated denervation of the motor units. This ultimately leads to muscle atrophy and myasthenia. Following an acute poliovirus infection, symptoms such as fatigue, asthenia, and pain are believed to be linked to muscle denervation.{{Cite journal|last1 = Gonzalez|first1 = Henrik|last2 = Olsson|first2 = Tomas|last3 = Borg|first3 = Kristian|title = Management of postpolio syndrome|journal = The Lancet Neurology|volume = 9|issue = 6|pages = 634–642|doi = 10.1016/s1474-4422(10)70095-8|pmid = 20494327|date = June 2010| s2cid=44657605 }}

Much like post-polio syndrome, ALS also has similar symptoms of motor neurodegeneration leading to general weakness and, in some cases, paralysis. The type of symptoms experienced can depend on which areas of the body experience the loss in nerve supply. This denervation process is different from post-polio syndrome in that it involves only upper and lower motor neuron degeneration and does not involve constant reinnervation and denervation.{{Cite web|url = http://0-hmg.oxfordjournals.org.libus.csd.mu.edu/content/24/25/7390.full|title = Millennium Web Catalog|website = 0-hmg.oxfordjournals.org.libus.csd.mu.edu|access-date = 2016-04-01}}{{dead link|date=May 2021|bot=medic}}{{cbignore|bot=medic}}

{{sa|Neurectomy}}

In addition to the management of peripheral nerve injury, denervation is used as a medical procedure for various benefits resulting from eliminating nerve supply to a specific area of the body. Renal denervation involves using radio frequency or ultrasound to eliminate the sympathetic nerve supply to the kidney wall, aiming to lower blood pressure and treat chronic hypertension.{{Cite journal|title = Renal sympathetic denervation in patients with treatment-resistant hypertension (The Symplicity HTN-2 Trial): a randomised controlled trial|journal = The Lancet|volume = 376|issue = 9756|pages = 1903–1909|doi = 10.1016/s0140-6736(10)62039-9|pmid=21093036|date=December 2010|vauthors=Esler MD, Krum H, Sobotka PA, Schlaich MP, Schmieder RE, Böhm M | s2cid=22838976 }} Renal denervation has become less common in recent years due to new evidence indicating that the procedure does not significantly lower blood pressure. Additionally, there are recommendations against its use, as there has been insufficient proof demonstrating that renal denervation effectively reduces blood pressure.{{Cite journal|last1 = Lobo|first1 = Melvin D.|last2 = Belder|first2 = Mark A. de|last3 = Cleveland|first3 = Trevor|last4 = Collier|first4 = David|last5 = Dasgupta|first5 = Indranil|last6 = Deanfield|first6 = John|last7 = Kapil|first7 = Vikas|last8 = Knight|first8 = Charles|last9 = Matson|first9 = Matthew|date = 2015-01-01|title = Joint UK societies' 2014 consensus statement on renal denervation for resistant hypertension|url= |journal = Heart|language = en|volume = 101|issue = 1|pages = 10–16|doi = 10.1136/heartjnl-2014-307029|issn = 1468-201X|pmc = 4283620|pmid = 25431461}}

Other prevalent surgical procedures involve intentionally reducing nerve supply to treat a variety of disorders. In a sympathectomy, a sympathetic ganglion is surgically removed to treat hyperhidrosis(excessive sweating).{{Cite journal|last1 = Cai|first1 = Song-Wang|last2 = Shen|first2 = Ning|last3 = Li|first3 = Dong-Xia|last4 = Wei|first4 = Bo|last5 = An|first5 = Jun|last6 = Zhang|first6 = Jun-Hang|last7 = Cai|first7 = Song-Wang|last8 = Shen|first8 = Ning|last9 = Li|first9 = Dong-Xia|title = Compensatory sweating after restricting or lowering the level of sympathectomy: a systematic review and meta-analysis|journal = Clinics|volume = 70|issue = 3|pages = 214–219|doi = 10.6061/clinics/2015(03)11|issn = 1807-5932|pmc = 4449481|pmid = 26017654|date = March 2015}} Surgical or radiologic ablation of the carotid sinus nerve is used to treat carotid sinus hypersensitivity.{{Cite book|url=https://www.ncbi.nlm.nih.gov/books/NBK559059/|title=StatPearls|first1=Antoine|last1=Kharsa|first2=Roopma|last2=Wadhwa|date=September 18, 2024|publisher=StatPearls Publishing|via=PubMed|pmid=32644485}} In a vagotomy, the vagus nerve is surgically removed to treat peptic ulcer disease by reducing stomach acid.{{Cite journal|last1 = Lagoo|first1 = Janaka|last2 = Pappas|first2 = Theodore N.|last3 = Perez|first3 = Alexander|title = A relic or still relevant: the narrowing role for vagotomy in the treatment of peptic ulcer disease|journal = The American Journal of Surgery|volume = 207|issue = 1|pages = 120–126|doi = 10.1016/j.amjsurg.2013.02.012|pmid = 24139666|date = January 2014}} In a rhizotomy, nerve fibers in the spinal cord are destroyed with the intent of eliminating chronic myalgia.{{Cite journal|last1 = Niemistö|first1 = Leena|last2 = Kalso|first2 = Eija|last3 = Malmivaara|first3 = Antti|last4 = Seitsalo|first4 = Seppo|last5 = Hurri|first5 = Heikki|title = Radiofrequency Denervation for Neck and Back Pain: A Systematic Review Within the Framework of the Cochrane Collaboration Back Review Group|journal = Spine|volume = 28|issue = 16|pages = 1877–1888|doi = 10.1097/01.brs.0000084682.02898.72|pmid = 12923479|year = 2003| s2cid=44963601 }}

In regard to skeletal muscle denervation there are two distinct diagnoses: entrapment and compressive neuropathies or non-entrapment neuropathies. Entrapment and compressive neuropathy syndromes occur due to compression and/or constriction on a specific location for a segment of a single nerve or multiple nerve sites. This entrapment or compression can be diagnosed based on multiple factors including physical examination, electrodiagnostic test and clinical history.{{Cite journal|last1 = Connor|first1 = S.E.J.|last2 = Chaudhary|first2 = N.|last3 = Fareedi|first3 = S.|last4 = Woo|first4 = E.K.|title = Imaging of muscular denervation secondary to motor cranial nerve dysfunction|journal = Clinical Radiology|volume = 61|issue = 8|pages = 659–669|doi = 10.1016/j.crad.2006.04.003|pmid = 16843749|date = August 2006}}

Following denervation, muscular atrophy and degeneration occurs within affected skeletal muscle tissue. Within the skeletal tissue is observable progressive loss of weight of denervated muscles as well as reduction in muscle fiber size and quantity. These muscles exhibit a slowing of contraction speed, a reduction of developed tension, and twitch force.

Magnetic resonance imaging (MRI) and high-resolution ultrasonography (US) are two clinical imaging examinations performed to classify the different diagnoses. Ultrasonography is advantageous with the evaluation of peripheral nerve resolutions while Magnetic Resonance Imaging is more sensitive in regard to signal intensity changes of the muscle.

Denervation affects the muscle activation process that is brought on by the development and propagation of an action potential and the ensuing release of calcium. It is found that there is an increase with calcium reuptake because of changes within sarcoplasmic reticulum morphology and structure. As a result, there is a decrease in amplitude and velocity of impulse conduction with an increase in muscle spike duration.

In clinical and experimental studies there is an observed increase in muscle excitability in electrical currents involving chemical actions, while there is a decrease in excitability to current associated with electrical induction in denervated muscles. Changes in the resting membrane potential involving denervated muscles presents mild depolarization when a muscle contraction stimulus is present. While there is no immediate change involving resting and action potential, there is an increase with membrane resistance. After prolonged denervation, it is revealed that resting membrane potential over time is reduced while action potentials progressively decreased and become slower. Acetylcholine is a neurotransmitter that becomes supersensitive in the presence of denervated muscle. Upon injection of acetylcholine, a slower contractile response, which is drastically under action potential threshold, is elicited.{{Cite journal|last = Midrio|first = Menotti|date = 2006-08-03|title = The denervated muscle: facts and hypotheses. A historical review|journal = European Journal of Applied Physiology|language = en|volume = 98|issue = 1|pages = 1–21|doi = 10.1007/s00421-006-0256-z|pmid = 16896733| s2cid=1993670 |issn = 1439-6319}}

Denervated muscles have shown the ability to survive after periods of denervation or in the case of a damaged nerve. The size of the nerve and its ability to function can be maintained if it is electrically stimulated soon after denervation, in clinical experiments. home-based functional electrical stimulation has been shown to rescue muscles which have experienced severe atrophy as a result of denervation.{{Cite journal|last1 = Carraro|first1 = Ugo|last2 = Boncompagni|first2 = Simona|last3 = Gobbo|first3 = Valerio|last4 = Rossini|first4 = Katia|last5 = Zampieri|first5 = Sandra|last6 = Mosole|first6 = Simone|last7 = Ravara|first7 = Barbara|last8 = Nori|first8 = Alessandra|last9 = Stramare|first9 = Roberto|date = 11 March 2015|title = Persistent muscle fiber regeneration in long term denervation. Past, present, future|url = http://pagepressjournals.org/index.php/bam/article/view/4832|journal = European Journal of Translational Myology|volume = 25|issue = 2|pages = 77–92|doi = 10.4081/ejtm.2015.4832|issn = 2037-7452|pmc = 4749009|pmid = 26913148}} This process involves electrically stimulating the nerves innervating the affected part of the body, using electrodes placed on the skin.{{citation needed|date=July 2021}}

For muscles that cannot be rescued via home-based functional electrical stimulation, an Italian study suggests that, at some point in the future, the following techniques may be applicable: they must first have induction and separation of autologous myogenic cells. This can be completed either by in vivo marcaine infiltration of muscle tissue that can then be grown in vitro, or have in vitro induction of autologous adipose tissue followed by selection of myogenic stem cells that can be recreated in vivo. The new autologous myogenic stem cells will be injected, proliferated and differentiated into new mature muscle fibers. Functional properties of these newly created muscle fibers will be induced via surface electrodes and an external neuromodulator.

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Category:Peripheral nervous system disorders