Denervation is any loss of

nerve A nerve is an enclosed, cable-like bundle of nerve fibers (called axons). Nerves have historically been considered the basic units of the peripheral nervous system. A nerve provides a common pathway for the Electrochemistry, electrochemical nerv ...

supply regardless of the cause. If the nerves lost to denervation are part of neural communication to an

organ system An organ system is a biological system consisting of a group of organ (biology), organs that work together to perform one or more bodily functions. Each organ has a specialized role in an organism body, and is made up of distinct Tissue (biolog ...

or for a specific tissue function, alterations to or compromise of physiological functioning can occur. Denervation can result from an injury or be a symptom of a disorder like

amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, Terminal illness, terminal neurodegenerative disease, neurodegenerative disorder that results i ...

(ALS),

post-polio syndrome Post-polio syndrome (PPS, poliomyelitis sequelae) is a group of latent symptoms of poliomyelitis (polio), occurring in more than 80% of polio infections. The symptoms are caused by the damaging effects of the viral infection on the nervous syst ...

, or neuropathic postural orthostatic tachycardia syndrome (POTS). Intentional denervation is a valuable surgical technique for managing some medical conditions, such as renal denervation in the setting of uncontrolled

hypertension Hypertension, also known as high blood pressure, is a Chronic condition, long-term Disease, medical condition in which the blood pressure in the artery, arteries is persistently elevated. High blood pressure usually does not cause symptoms i ...

. Pathological denervation, by contrast, is associated with serious health sequelae, including increased infection susceptibility and tissue dysfunction.

Causes

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

Injuries

Denervation can occur as a consequence of nerve injury. The three primary categories of nerve injury are neurapraxia,

axonotmesis Axonotmesis is an injury to the peripheral nerve of one of the extremities of the body. The axons and their myelin sheath are damaged in this kind of injury, but the endoneurium, perineurium and epineurium remain intact. Motor and sensory function ...

, 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.

Disorders

Denervation processes are strongly associated with the symptoms experienced in

. 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 Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakne ...

and myasthenia. Following an acute poliovirus infection, symptoms such as

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

, asthenia, and

pain Pain is a distressing feeling often caused by intense or damaging Stimulus (physiology), stimuli. The International Association for the Study of Pain defines pain as "an unpleasant sense, sensory and emotional experience associated with, or res ...

are believed to be linked to muscle denervation. Much like post-polio syndrome,

ALS Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and low ...

also has similar symptoms of motor

neurodegeneration A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their cell death, death. Neurodegenerative diseases include amyotrophic lateral sc ...

leading to general weakness and, in some cases,

paralysis Paralysis (: paralyses; also known as plegia) is a loss of Motor skill, motor function in one or more Skeletal muscle, muscles. Paralysis can also be accompanied by a loss of feeling (sensory loss) in the affected area if there is sensory d ...

. 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.

Surgical procedures

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 Radio frequency (RF) is the oscillation rate of an alternating electric current or voltage or of a magnetic, electric or electromagnetic field or mechanical system in the frequency range from around to around . This is roughly between the u ...

ultrasound Ultrasound is sound with frequency, frequencies greater than 20 Hertz, kilohertz. This frequency is the approximate upper audible hearing range, limit of human hearing in healthy young adults. The physical principles of acoustic waves apply ...

to eliminate the sympathetic nerve supply to the kidney wall, aiming to lower blood pressure and treat chronic hypertension. 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. 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 Hyperhidrosis is a medical condition in which a person exhibits excessive perspiration, sweating, more than is required for the Thermoregulation, regulation of body temperature. Although it is primarily a physical burden, hyperhidrosis can deterio ...

(excessive sweating). Surgical or radiologic ablation of the carotid sinus nerve is used to treat carotid sinus hypersensitivity. In a vagotomy, the

vagus nerve The vagus nerve, also known as the tenth cranial nerve (CN X), plays a crucial role in the autonomic nervous system, which is responsible for regulating involuntary functions within the human body. This nerve carries both sensory and motor fibe ...

is surgically removed to treat

peptic ulcer disease Peptic ulcer disease is when the inner part of the stomach's gastric mucosa (lining of the stomach), the first part of the small intestine, or sometimes the lower esophagus, gets damaged. An ulcer in the stomach is called a gastric ulcer, while ...

by reducing

stomach acid Gastric acid or stomach acid is the acidic component – hydrochloric acid – of gastric juice, produced by parietal cells in the gastric glands of the stomach lining. In humans, the pH is between one and three, much lower than most other an ...

. In a rhizotomy, nerve fibers in the

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

are destroyed with the intent of eliminating chronic

myalgia Myalgia or muscle pain is a painful sensation evolving from muscle tissue. It is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likely cause is viral infection, espec ...

Physiological differences

In regard to skeletal muscle denervation there are two distinct diagnoses: entrapment and compressive

neuropathies Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

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. 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 Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...

(MRI) and high-resolution

ultrasonography Medical ultrasound includes diagnostic techniques (mainly imaging) using ultrasound, as well as therapeutic applications of ultrasound. In diagnosis, it is used to create an image of internal body structures such as tendons, muscles, joints, ...

(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 Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

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.

Reinnervation possibilities

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. This process involves electrically stimulating the nerves innervating the affected part of the body, using electrodes placed on the skin. 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 Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

marcaine infiltration of muscle tissue that can then be grown

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

, 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.

References

{{reflist Peripheral nervous system disorders