Peripheral neuropathy (PN) involves a disruption of the action potential transmission in peripheral nerves, either through the deterioration of the axon, axonopathy, or the deterioration of the myelin sheath, myelinopathy. This causes tingling sensations, numbing, temperature disparity or pain in the digits and limbs of the patient. The first form of genetic PN includes genetic code mutations, and the second form of PN is acquired by chemicals, toxins, nutritional deficiency, and tumors. Although many acquired causes can be identified for PN, diabetes mellitus is the most frequently diagnosed (Daousi et al 2006). “Peripheral Neuropathy can be the result of genetics, chronic disease, environmental toxins, alcoholism, nutritional deficiencies, or side effects of certain medications. Among chronic diseases, diabetes mellitus is the most common cause of PN” (Head, 2006). The focus of this paper is to explore axonopathy and myelinopathy within the context of acquired diabetic peripheral neuropathy, which, according to Koopman et al 2006, represents “a serious public health concern.”
Nervous tissues consist of highly-specialized cells that conduct action potentials to and from the central and peripheral nervous systems. A neuron is the basic cell of the system and it is composed of a neural cell body that extends into an axon. This axon is swathed in a myelin material from Schwann cell membranes that facilitate the conduction of an action potential. “During the wrapping process, the cytoplasm is squeezed from between the adjacent layers of Schwann cell membranes, so that when the process is completed a tight coil of plasma membrane material (protein-lipoid material) encompasses the axon” (Marieb and Mitchell, 2007). This axon and myelin have an exact composition and overall proportion for optimum conductivity, “maximum insulating ability, and maximum protection. Myelin is composed mainly of lipid, but also contains a number of myelin-specific structural proteins” (van Gemert & Killeen, 1997). Due to the specifications of the axon and myelin, neuropathy can result from any chemical, tumor, nutritional deficiency, or toxic tampering.
Acquired PN develops during a continuous or intermittent exposure to a damaging substance or nutritional deficiency through vasoconstriction. A damaging substance such as a radical or toxin can attack the axon first and myelin secondary, causing axonopathy, or attack the myelin alone, causing myelinopathy. Axonopathy and myelinopathy are distinguished by the specific effects of the attacking substance, or by the specific effects of a hindrance on the neuron’s health. A tumor growth can cause nutritional and vascular deficiency in axonopathy and myelinopathy, which stymies the neuron’s ability for action potential conduction.
Axonopathy and myelinopathy are jointly involved in diabetic neuropathy. Both disorders inhibit the proper conduction of an action potential leading to neuropathic symptoms, and the effects are acute. Symptoms are pain, numbness, loss of temperature differentiation, loss of reflex, loss of balance, inflammation, erectile dysfunction, and inability to distinguish small objects by touch are commonly exhibited. These issues, especially the pain, greatly affect the patient’s quality of life. Seventy-five percent of diabetic patients report moderate to severe pain as a primary symptom of diabetic neuropathies, according to Cocito et al 2006.
In diabetic axonopathy, demyelination is a secondary event to the destruction of the axon. “Axonal degeneration is the primary event, and this eventually results in fiber loss with the attendant removal of the myelin sheath” (Spencer and Shaumburg, 1978). The axon destruction is caused by vasoconstriction, and soon neuronal hypoxia and ischemia develops. Also, osmotic stress caused by free-floating polyls and metabolic toxins develops around the axon during the diabetic hyperglycemic state.
Diabetic myelinopathy affects a broad spectrum of distal nerves at a time, demonstrating that “primary demyelination would be scattered. . . not limited to any one nerve fiber.” (Spencer and Shaumburg, 1978). There are two basic types of primary demeylinators that cause myelinopathy. “Some demyelinating chemicals seem to leave intact the myelinating cells (Schwann cells), while others damage the myelinating cells as well as the myelin. The significance between the two is that with the myelinating cells still intact, repair of the myelin sheath is possible. “Regeneration of the myelin layers can occur, and in some cases occurs at the same time other axons are undergoing toxic demyelination” (van Gemert & Killeen, 1997).
Regeneration of axons and myelin sheath relies on length of exposure, what factors were attacked to cause the neuropathy, and the “trophic support” that remains intact. “Trophic support in a general sense encompasses any proteins or group of proteins that could influence the survival of the axon” (Madison, Robinson and Chadaram, 2007). Proteins include growth factors such as neurotrophin-3, glia-derived neurotrophic factor, and fibroblast growth factors. “Recent studies have shown the development of oligondendrocytes and the synthesis of myelin are extensively controlled by growth factors” (van Gemert & Killeen, 1997). Research involving growth protein supplementing in diabetic patients that could improve the regeneration of deteriorated or un-functional neurons.
Diabetes mellenitus affects 20.8 million, or 7%, of children and adults in the United States, with an estimation of 6.2 million people living undiagnosed, according to the American Diabetes Association. The statistics cited for the proportion of diabetic patients with peripheral neuropathy range from 21% to 63.9%, compared to 10% in patients without diabetes (Koopman et al 2006; Janghorbani et al 2006; Head, 2006). Since diabetes is incurable, and since the symptoms directly deteriorate peripheral nerves, these statistics are alarming. Factors that affect neuropathic regression include diabetic duration, age, body mass index, metabolic control, hemodynamic vascularation factors, oxidative stress, and duration of hypertension.
According to Jarmuzewska et al 2006, hypertension serves as the primary inducer of diabetic neuropathy, and diabetes duration and metabolic imbalance are involved in its progression. According to Sawant et al 2007, oxidative stress on neurons by free-radical formation and a defect in antidioxidant defenses will induce also neuropathy. “An imbalance between the generation and savaging of these free radicals leads to ‘oxidative stress’, which may be associated. . . with nerve damage leading to diabetic neuropathy” (Sawant et al 2007). The accumulation of glucose and glycosylated proteins can produce damaging toxins which generate up to 50 times the nerve-damaging free radicals. “Not only are nerve cells more likely to be destroyed in a hyperglycemic environment, but repair mechanisms are also defective” (Head, 2007).
Diabetic control is paramount in maintaining nerve function and staving off extensive peripheral neuropathy. Glucose-level management through insulin therapy and hypertension reduction through anti-depressant therapy are two primary methods. Maintaining both these factors in a diabetic patient should be accompanied with a nutritious diet to improve the immune-system’s ability to irradiate free-radicals, states Jarmuzewska et al 2006. Metabolic control is stressed by Janghorbani et al 2006 as a necessity for PN prevention by not allowing the hyperglycemic environment to thrive. In regards to the patient’s quality of life, Dousi et al 2006 maintains that the pain in diabetic PN remains under-treated due to the reluctance of medical staff to prescribe the appropriate strength of pain-killers for the patient’s relief.
In chronic diabetic neuropathy, symptoms improved over five years of therapies and diabetes-controlling medicine in 23% of diabetic patients (Daousi et al 2006). Diabetic patients with PN are treated with a variety of antidepressants, anticonvulsants, antiarrhythmics, opioid and non-opioid analgesics, and aldose reductase inhibitors to preempt the many symptoms of PN. Cocito et al 2006 maintained that pain was the primary symptom that lowered the patient’s quality of life, and recommended that appropriate pain-killers should be administered. The quality of life increased overall when diabetic patients complied with rigorous glucose-control and a strict diet that fostered the immune-system’s ability to eradicate free radicals and damaging substances while improving neural vascularation.
PN proves to be a complex medical issue, primarily due to the myriad of ways the neural tissue can be damaged, particularly by diabetes mellitus. Simplistically stated, the neuron with its action potential pathway in the peripheral nervous system can be effortlessly destroyed in the glucose-saturated and immune-deficient diabetic host – what remains undetermined are the precise causative factors and the interplay between each other and the neuron. Regeneration of the neuron and reacquisition of neural function after deterioration is a delicate process that can occur only if the myelinating cells and trophic support remain intact. The quality of life for diabetic patients can be promoted through a stringent medical and dietary regimen that manages glucose levels and through minimizing the PN symptoms by sufficient pain-killing drugs.
Dr. Bishop of the University of Alabama in Huntsville states that future research should involve using growth factors to foster trophic support in neurons. Other further research should involve reducing oxidative stress by preventing the formation of free radicals and toxic metabolic by-products and averting chronic hypertension in diabetic patients.
References
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