|Year : 2013 | Volume
| Issue : 4 | Page : 332-334
Department of Anesthesiology, Yale University School of Medicine, New Haven, USA
|Date of Submission||03-May-2013|
|Date of Acceptance||28-Apr-2013|
|Date of Web Publication||15-Oct-2013|
Department of Anesthesiology, Yale University School of Medicine, New Haven
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Diabetic neuropathy is a serious complication of diabetes as a result of nerve damage from long term diabetes. Oxidative stress can lead to cell damage which in painful diabetic neuropathy can be associated with peripheral and central sensitization and increased pain. The most common sites of pain are in the periphery involving the feet, toes, and hands. It is recommended that foot exams be done every year in patients with long standing diabetes to prevent diabetic neuropathy. Nerve conduction tests and electromyograms are important tests to detect diabetic neuropathy. Several drugs that have phytochemicals/plant extracts have been tried for the treatment of Diabetic Neuropathy. Research for the treatment of diabetic neuropathy is also ongoing in the field of gene therapy.
Keywords: Central sensitization, diabetic neuropathy, peripheral sensitization, tests for diabetic neuropathy, treatment of diabetic neuropathy
|How to cite this article:|
Vadivelu N. Diabetic neuropathy. Int J Nutr Pharmacol Neurol Dis 2013;3:332-4
Diabetes affects about 150 million people in the world. It is associated with impaired carbohydrate metabolism and hyperglycemia. It is associated with serious complications such as diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy (DN). DN is a result of nerve damage and is a significant problem in patients with diabetes mellitus (DM). DN can occur usually 10-20 years after the diagnosis of diabetes. DN is more common in patients with long duration of diabetes and inpatients with increased patient age.  The prevalence of DN in DM varies from 14% to 63% depending upon the criteria used to define DN.
| Mechanisms of DN|| |
The pathogenic mechanism of the development of painful DN is not completely understood and observations have led to several postulations.  Research is still underway to better understand the mechanisms of DN. Oxidative stress has been determined to play a crucial role in a wide spectrum of disease states including diabetes at the cellular and molecular levels.  Structure and function of chromosomes can change because of oxidative stress in chronic disease conditions including diabetes. Several techniques have been developed in the last few decades to assess the extent of chromosomal damage in patients with DM in order to detect genotoxic effects of oxidative stress Some studies have reported a significant increase in chromosomal aberration frequency and sister chromatid exchange in Type 2 DM patients compared with those of healthy controls. However, reports on the association between DN and genotoxic effects are rare.
Cell damage in painful DN can be followed by both peripheral and central sensitization nociceptor activation and sensitization painful DN results in cell damage and release of arachidonic acid, potassium and hydrogen ions as well as the up regulation of cyclooxygenase II leading to the increased synthesis of prostaglandins.
Prostaglandins and bradykinin sensitize the nociceptor endings. Other substances are also involved in the sensitization of peripheral nociceptors. These include the Release of norepinephrine from sympathetic efferent fibers and the release of neurogenic peptides including substance P, which leads in turn to the release of histamine, vasodilatation, and edema.
| Transduction and Transmission|| |
The process by which the peripheral nociceptor becomes activated is termed transduction. Transmission refers to the propogation of action potentials to the spinal cord. In the process of transmission, the primary afferent pain fibers are the small unmyelinated C fibers and large a-delta fibers, which initially reach the substantia gelatinosa ultimately and synapse in second order neurons in the dorsal horn in Lamina I and Lamina V.
| Terms in Central Sensitizations|| |
Windup: Increased and prolonged discharge of dorsal horn cells central hyper excitability Long-term potentiation: Cellular memory of pain and response. Biochemical mediators in central sensitization include excitatory amino acid (glutamate), neuropeptides (substance P), N-methyl-d-aspartate receptor: Keyrole in windup, second messenger (G proteins), protein kinase C, proto-oncogenes (C-fos, C-jun).
| Pain Perception|| |
Net result of peripheral and central neuronal sensitization and a balance between the excitatory and inhibitory function within the nervous system.
| Presentations of Diabetes Neuropathy|| |
DN patients demonstrate varied abnormal sensations, including paresthesias, allodynia, hyperalgesia, and spontaneous pain, which can negatively affect their quality of life. The most common nerves damaged with the loss of feeling and pain occurs in the legs, feet, toes, arms, and hands. Nerve injuries from the spinal column and branches and nerves in the skull can also be affected. 
The prevalence of pain varies from 40% to 50% in DN patients usually can complain of pain in different sites.
- Peripheral pain or loss of feeling in upper and lower extremities
- Proximal pain in thighs, and weakness in legs
- Focal sudden weakness of one nerve or a group of nerves, resulting in pain and muscle weakness and entrapment syndromes
- Autonomic system affecting the digestion, bowel and bladder function, and perspiration.
| Natural History of DN|| |
- Irreversible nerve fiber degeneration
- Delay in nerve conduction
- Demyelination of peripheral nerves
- Possible reduction of prostacyclin in vascular tissues and peripheral nerves.
| Common Tests for Diagnosis of DN|| |
Common medications used for the treatment of DN include:
- Foot exams are recommended to be done each year in patients with diabetes to test pressure sensation, temperature perception, and vibration perception
- Nerve conduction velocity tests a recording of the speed of travel of signals and
- Electromyogram recording electrical activity is important tests to detect DN.
- Amytriptaline (Elavil)
- Duloxetine (Cymbalta)
- Doxepin (Sinequan)
- Pregabalin (Lyrica)
- Neurontin (gabapentin)
- Valproate (Depakote)
- Carbamazapine (Tegretol).
| Phytochemicals and Plant Extracts on DN|| |
There is recent increased interest in the use of phytochemicals extracted from traditional medical plants for the treatment of diabetes and its complications including DN. It has been reported that anti-diabetic medicinal plants can act at different levels including of glucose transporters, inhibition of carbohydrate hydrolyzing enzymes, a-amylase and a-glucosidase.
| Tea Polyphenolics|| |
In addition to the antioxidant property, tea polyphenolics have been reported to inhibit the enzymes amylase and sucrase, and have been shown to be important substance for suppressing post-prandial hyperglycemia. These polyphenolics have also been reported in addition to decrease the transport of glucose across the intestine.
Gymnema sylvestre, is an Indian medicinal plant, called (Gurmar) in Hindi which means sugar destroyer known to be an anti-diabetic for many centuries. This name is attributed to the plant owing to its sweet-taste suppressing property. A variety of actions have been seen with extract from this plant like reduction in the requirement of insulin possibly by enhancing endogenous insulin requirement possibly by enhancing endogenous insulin.
Zizyphusjujuba is another plant extract that has been shown to have some anti-diabetic activity in rats. Research is ongoing in this area.
Trigonellafoenum-graceum (Fenugreek seeds)
Fenugreek seeds is also called in Hindi as methi. Effects seen with methi seeds include hypoglycemic, antioxidant and hypolipidemic properties in animal and human experiments as well as in human and clinical cases.
Ocimum sanctum is called in Hindi as (Tulasi) or the holy basil and O album have been observed to decrease the fasting post prandial blood and urinary glucose levels in Type 2 diabetic patients.
Myrciamultiflora is a Brazalian medicinal plant has been called plant insulin has been found to have flavanol and flavanone glucosides inhibiting the enzyme aldose reductase and the inhibition of the enzyme glucosidase.
Mechanism of action of phytochemicals and plant extracts in the treatment of complications of diabetes
Challenges of painful DN
- Inhibition of aldose reductase, is a key enzyme of the polyol pathway, has been demonstrated to play an important role in etiopathology of diabetic complications such as neuropathy, cataract, retinopathy, and nephropathy
- Antioxidant activity
- Mitigating the oxidation of glucose glycation, and decrease the release of free radicals.
DN is a disabling disease with resultant loss of work hours. In addition, it can last for several years and be very difficult to treat. There are several drugs that have been tried as well as effects of phytochemicals/plant extracts for the treatment of DN. Research is ongoing in this field including gene therapy.
| References|| |
|1.||Adler AI, Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Smith DG. Risk factors for diabetic peripheral sensory neuropathy. Results of the seattle prospective diabetic foot study. Diabetes care 1997;20:1162-7. |
|2.||Calcutt NA. Potential mechanisms of neuropathic pain in diabetes. Int Rev Neurobiol 2002;50:205-28. |
|3.||Domínguez C, Ruiz E, Gussinye M, Carrascosa A. Oxidative stress at onset and in early stages of type 1 diabetes in children and adolescents. Diabetes Care 1998;21:1736-42. |
|4.||Veves A, Backonja M, Malik RA. Painful diabetic neuropathy: Epidemiology, natural history, early diagnosis, and treatment options. Pain Med 2008;9:660-74. |