A-beta fibers, the largest, which mediate the sensations of touch and mild pressure, as well as the sensation of the position of joints and vibration, at a conduction velocity above 30 m/sec.
A-delta fibers, smaller than A-beta fibers, which mediate the sensation of cold and the first components of the sensation of pain, at a conduction velocity between 2 and 30 m/sec.
C fibers, the slowest and smallest, which mediate the sensation of warmth and constitute the secondary component of pain, at a conduction velocity less than 2 m/sec.
Small-caliber fibers (i.e., A-delta & C-fibers) constitute 70% of the peripheral nerve system. C and A-delta fibers are the only fibers responsible for pain transmission that extends from the periphery to the spinal cord and to the brain and also known as The Pain Pathway.
Traditionally, the clinical assessment of neural dysfunction consists solely of clinical examinations and nerve conduction velocity, as well as muscle electrical activity (EMG) sampling. This is limited to only the large, and fast, peripheral nerve fibers and ignores 70% of the sensory nerve fibers.
There are several diseases that affect peripheral nerves. Some affect the entire fiber spectrum, others are more selective. These include metabolic diseases such as diabetes mellitus and uremia, chronic alcohol abuse, local compression of a peripheral nerve such as carpal tunnel syndrome and nerve injuries such as CRPS or trauma.
Medoc’s introduction of QST and PATHWAY systems allowed clinicians to test small nerve fibers by assessing thresholds for warmth, cold, heat-induced pain and cold-induced pain, as well as objective, evoked pain response, recorded directly from the scalp. These technologically advanced systems enable both quantitative and objective measurement of sensation and pain thresholds, matched with an age-matched normal population value database.
Peripheral neuropathy describes damage to the peripheral nervous system which may be caused either by diseases of or trauma to the nerve or the side effects of systemic illness.
The human nervous system can be broadly divided into two categories: the Central Nervous System (CNS) and the Peripheral Nervous System (PNS). The central nervous system is comprised of the brain and the spinal cord. The peripheral nervous system includes the sensory nerves which carry information from receptors to the CNS and motor nerves which convey information from the CNS to the effectors that are involved in muscular control.
Structures in the Peripheral Nervous System
Peripheral nerves consist of fibers of variable diameter. Small caliber nerve fibers comprise of thinly myelinated A-delta fibers and unmyelinated C-fibers. A-delta fibers mediate cold sensation and participate in the quick and well-localized aspects of nociception. C-fibers convey warm and nociceptive (painful) stimuli, mainly the dull, long term and less localized aspects of the pain experience. Sensory large-caliber nerve fibers include A-beta fibers, which mediate sensations of touch, mild pressure and position of joints.
Peripheral nerves also send sensory information back to the brain and spinal cord, such as a message that the feet are cold or a finger is burned. Damage to the peripheral nervous system interferes with these vital connections. Peripheral neuropathy distorts interrupts messages between the brain and the rest of the body.
The most common form of peripheral neuropathy is (symmetrical) peripheral polyneuropathy, which mainly affects the feet and legs. Frequently the cause of a neuropathy cannot be identified, and it is designated as being idiopathic.
Variety of Symptoms
Because every peripheral nerve has a highly specialized function in a specific part of the body, there is a variety of symptoms that can occur when nerves are damaged, starting from temporary numbness, tingling, and pricking sensations, sensitivity to touch, muscle weakness, burning pain (especially at night) and ending with muscle wasting, paralysis and organ or gland dysfunction. People may become unable to digest food easily, maintain safe levels of blood pressure, or sweat normally. In the most extreme cases, breathing may become difficult or organ failure may occur.
Small Fiber Neuropathy
Small Fiber Neuropathy (SFN) refers to a subtype of peripheral neuropathies characterized by the impairment of thinly myelinated A-delta and unmyelinated C-fibers. SFN is a relatively common disorder resulting in severe and troublesome symptoms (relating to somatic and autonomic nerve fiber impairment), which may be difficult to control.
Standard electrophysiological tests such as nerve conduction studies (NCS) and EMG remain normal in SFN, therefore, the syndrome may easily be overlooked. NCS and EMG reflect only large fiber function, leaving small fiber function unrepresented.
Quantitative Sensory Testing for Diagnosing Small Fiber Neuropathy
Small fiber functions are most commonly investigated by Quantitative Sensory Testing (QST) devices for the determination of perception thresholds to warm and cold, as well as for the detection of pain threshold. Recent works have shown that warm and heat-pain threshold correlated with quantification of intraepidermal nerve fiber (IENF) density. IENF are somatic unmyelinated C-fibres, which density can be quantified with a skin biopsy. Skin biopsy can demonstrate the loss of IENF in SFN, however, this technique is invasive and in some cases such as in Diabetic neuropathy even harmful.
Diagnosing patients complaining of symptoms suggesting SNF is important for at least three main reasons: First, the definition of the diagnosis can lead to a focused screening on its etiology. Second, early disease modifying or symptomatic treatments can be started. Third, the awareness of the disease can increase patients’ compliance, which is particularly important in treatment of neuropathic pain.
Evoked potentials are electrical potentials recorded from the nervous system following a stimulus, and are different from spontaneous potentials as detected by electroencephalography (EEG), electromyography (EMG), or another electrophysiological recording method. Signals can be recorded from cerebral cortex, brain stem, spinal cord and peripheral nerves. Usually the term “evoked potential” is reserved for responses involving either recording from or stimulation of, central nervous system structures.
Small-fiber Evoked Potentials
Small-fiber Evoked Potentials (EPs) to sensory (non-painful) and noxious thermal stimulation of skin can provide quantitative, objective information about the integrity of the nociceptive afferents as part of the peripheral nerve system.
Contact Heat Evoked Potentials
Contact heat evoked potentials (CHEPs) represent synchronized brain response to brief heat stimuli. When applied to the hairy skin, CHEPs amplitude and latency reflect the functioning of thin militated A-delta sensory fibers; the stimulation of glabrous skin, in turn, evoke C-fiber evoked potential and reflects the functioning of unmyelinated sensory fibers. Since 2005, when the first CHEPs-related article was published, this type of neurophysiological response to heat-pain-evoked stimulation of thermo-receptors became a feasible wide-used tool for the pain. CHEPs assessment provides quantitative, objective information about the integrity of peripheral and central nociceptive pathways, and is clinically useful in the diagnosis of a variety of disorders affecting sensory small fibers. The CHEPS is easier to operate and maintain than the laser EPs, avoids the risk of superficial burns, it is also safe to use in patients in the trigeminal region.
According to a recent publication of the Assessment Committee of the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP), use of pain EPs (CHEPs or laser EPs) is recommended for the assessment of the function of A-delta fibers in neuropathic pain.
Wide range of applications
Objective response to thermal-evoked pain, as influenced by medications & treatments, opens a wide range of new research and pharmacological evaluation opportunities, using CHEPs as an indicator of drug efficacy and its specification, thus serving as a “surrogate endpoint”. Furthermore, since hyperactivation of peripheral and central pain pathways at various chronic pain states (such as fibromyalgia, low back pain, and neuropathic pain syndromes) is reflected by changes in pain EPs characteristics, CHEPs may have potential future clinical use.
Diabetic neuropathy is damage to nerves in the body that occurs due to high blood sugar levels from diabetes, and related decreased blood flow. Over time excess blood glucose can injure the walls of tiny blood vessels that nourish the nerves, especially in the legs. Nerve injuries are more likely to develop if blood sugar levels are not well controlled. In the USA 15-20 million people over the age of 40 have neuropathy. About half of people with diabetes will develop nerve damage. In an advanced stage, the neuropathic changes may affect the functioning of cranial nerves, nerves from the spinal column and their branches and nerves that help the body manage vital organs, such as the heart, bladder, stomach, and intestines (called autonomic neuropathy).
Most of the neuropathic symptoms do not begin until 10 to 20 years after diabetes has been diagnosed and can vary depending on the nerves that are affected. The most common symptoms are: tingling or burning in the arms and legs (which may be an early sign of nerve damage), deep pain, often in the feet and legs, trouble digesting food, excessive sweating, bladder problems, and sexual problems.
Bladder and kidney infections
Injury to the feet due to loss of feeling
Poor blood sugar control due to nausea and vomiting
Skin and soft tissue damage and risk of amputation
A diabetic neuropathy diagnosis is made on the basis of symptoms (as mentioned above) and a physical exam (blood pressure and heart rate, muscle strength, reflexes, sensitivity to position, vibration, temperature, or light touch).
Also, the doctor may run other tests to help make a diabetic neuropathy diagnosis and determine the type and extent of nerve damage.
These tests may include:
Quantitative sensory testing (QST)
Heart rate variability
Nerve or skin biopsy
Quantitative sensory testing (QST) implies sensory stimuli (such as pressure, vibration, and temperature) to check for neuropathy. QST is increasingly used to recognize sensation loss and excessive irritability of nerves.
Diabetic neuropathy is the clinical field in which QST has been most commonly applied, covering every aspect of the neuropathy, from diagnosis to therapy. QST was suggested as a tool for staging diabetic neuropathy by assessing the presence and severity of the neuropathy based on the degree of warm and cold threshold abnormality. There is a significant correlation between the thermal abnormalities and the clinical bedside examination of small fiber function suggesting that these criteria could be used for long-term assessment of patients.
Small fiber neuropathy is considered to be the most common complication of diabetes. As the population continues to age and as more patients develop diabetes and other metabolic syndromes, the prevalence of such small fiber neuropathies will rise.
The intensity of pain in painful Diabetic Peripheral Neuropathy (DPN) seems to depend on small nerve fiber damage which can be assessed with thermal QST. Importantly, QST can detect early dysfunction of the unmyelinated fibers in DPN. Subclinical detection can reduce severe neurological complications and make possible an early and effective treatment. These findings prove the importance of thermal QST for the early detection of neuropathy in diabetics and thus indicate the need for better glucose control as well as a change in lifestyle and diet. Furthermore, QST in diabetic neuropathy may be valuable in providing quantitative data in longitudinal natural history or clinical trial studies, in which thresholds can be measured over a long time period.
The major result of many studies indicated that thermal sensitivity is altered in asymptomatic patients. This result is significant because the method used to study thermal sensibility (QST) is semi-objective, low cost, reproducible and above all non-invasive or painful. This method enables clinicians to detect early diabetic neuropathy and allows effective and prompt treatment with normalization of the blood glucose.
Functional and organic abnormalities in small unmyelinated C fibers are the hallmark of type 2 diabetes. These may be silent clinically or present with burning feet, neurovascular abnormalities, wherein warm, cold, and heat pain thresholds are disturbed in association with impairment in skin blood flow and loss of PGP 9.5 immunostaining nerves in the skin.
Aggressive cause-specific treatment, lifestyle modification, and pain control are key elements of a team approach to managing small fiber neuropathy.
Patients with diabetic peripheral neuropathy require more frequent follow-up, with particular attention to foot inspection to reinforce the need for regular self-care. The provision of regular foot examinations and reinforcement of the educational message on foot care has been shown in several studies to significantly reduce rates of ulceration and even amputation.
Early detection enables the doctor to recommend a healthy and suitable diet and lifestyle and therefore the medical treatment can be postponed. Early detection is essential since in certain cases, small nerve fibers can regenerate.
The goals of management of diabetic patients are to provide relief from diabetic symptoms and improvement of quality of life and prevention of acute complications.
Keeping blood glucose levels on target may help prevent or delay nerve damage. If nerve damage already exists, this will help prevent or delay further damage.
Treatment would include keeping the blood sugar in a healthy range by a special diet, exercise, and sometimes medicines. In any case, early detection is essential.
Pain is an unpleasant feeling often caused by intense or damaging stimuli or injury.
Pain can become chronic if it lasts beyond the term of a painful stimulus or an injury and more than the anticipated healing period (6 months is a consensus). With chronic pain, signals of pain remain active in the nervous system for weeks, months, or even years. This can take both a physical and emotional toll on a person. As opposed to acute pain, chronic pain is not only a symptom but rather a disease on its own.
Causes of Chronic Pain
Chronic pain is a part of many medical conditions or injuries. Some people will continue to experience pain long after recovering from an initial injury, such as back or spine injury. Other chronic pain is caused by chronic diseases such as arthritis, fibromyalgia or cancer or by many neuropathies such as Diabetic painful neuropathy. Some people have pain that is caused by nerve inflammation or damage or even pain that does not have an identifiable cause (idiopathic). Whatever the cause, chronic pain is real and should be treated.
Types of Chronic Pain
Chronic pain may be divided into “nociceptive” (caused by activation of nociceptors in the skin), and “neuropathic” (caused by damage to or malfunction of the nervous system). Neuropathic pain is divided into “peripheral” (originating in the peripheral nervous system) and “central” (originating in the brain or spinal cord). Peripheral neuropathic pain is often described as “burning”, “tingling”, “electrical”, “stabbing”, or “pins and needles”.
The Importance of Diagnosing Chronic Pain
As in all good medical practices, good treatment planning can only be based on accurate diagnosis. Chronic pain is a disease and for its successful management, requires the recognition of a source and therefore, diagnosis. The earlier the diagnosis, the better is the outcome. Early diagnosis enables deciding on the proper treatment and may prevent the worsening of the condition or disease.