Diabetic Neuropathy and Possible Treatment

Abstract

To the Editor:—Insulin-dependent diabetes mellitus is commonly associated with increasing incidence of neurovascular complications with age.1-3 Age-associated vascular changes include a slowly continuous and symmetrical thickening of vessel walls, due in part to deposition of connective tissue and smooth muscle cells and to an increased percentage of lipid substitution into vascular layers.4, 5 The diabetic contribution affects vessel stiffening, flow dynamics, shear forces, and loss of sympathetic vasoconstrictor tone,2, 5 resulting in impaired venous return and perfusion of tissues.5, 6 The involvement of vascular abnormalities in the pathogenesis of diabetic neuropathy is suggested by animal studies indicating faulty regulation of the microcirculation and oxygen delivery systems.5, 7 Diabetic neuropathic processes are now regarded as the most common cause of peripheral neuropathies,1, 2 ultimately affecting up to 50% of patients with long-term diabetes.1, 5 The most common type is a distal-symmetrical sensory pattern1-3, 5 accompanied by dysesthesias and paresthesias.1, 2 Evolution of sensory-pain tract involvement is in a centripetal pattern,3 which may lead to a distribution of paralysis,5 particularly to distal affected areas.3 Persistent pain to the lower legs and feet can become severe and functionally disruptive despite regulated maintenance of serum glucose levels.2, 3 The most difficult aspect of diabetic neuropathic management is treatment of pain.8 Analgesics, antidepressants, anticonvulsants, and vitamin supplements have all been advocated, with little evidence of efficacy.8 We are interested to learn if nitroglycerine 2% in ointment form, (Nitro-Bid), a compound with local vasodilating properties, might affect impaired peripheral circulation and reduce pain associated with neurovascular changes and neuropathy in insulin-dependent diabetes mellitus. We present two brief cases of diabetic peripheral neuropathy treated empirically with nitroglycerine 2% ointment. We are not aware of the previous use of nitroglycerine 2% ointment for neurovascular disease. Ms. S was an 81-year-old female with end-stage arthritis and insulin-dependent diabetes mellitus who resided in a long-term skilled nursing facility. She suffered severe nocturnal peripheral neuropathy that left her insomniac. Because of impaired renal function, analgesics were not well tolerated. A trial of nitroglycerin 2% ointment was applied to the pedal areas and covered by socks at bedtime. Subjectively, and by nurse report, Ms. S was able to obtain some symptomatic relief, and sleep improved after the third evening of application. Mr. B is a 57-year-old man, with diabetic peripheral neuropathy. The discomfort, exacerbated by weight bearing, was blamed for his insomnia. A trial of lorazepam (Ativan) and trazodone (Desyrel), for his complaints of insomnia failed to offer sustained relief. A bedtime application of nitroglycerin 2% ointment was begun. After 5 days of treatment, Mr. B reported that he was able to stand at the race track and, further, that his sleep was improved. His pain persisted, but at a more tolerable level. There is no follow up on the above patients as Ms. S died shortly after initial contact, and Mr. B became non-compliant for his out-patient follow-up appointments. The accumulative vascular changes of aging and diabetes affect vessel plasticity, hemodynamic tolerance, nutrient transport capacity, and hemorrheologic threshold.5 The theorized benefits of nitroglycerine 2% ointment treatments for neurovascular abnormalities rest in its principal pharmacological action as a locally acting vasodilator of veins more than arteries and vascular smooth muscle;9 conceivably these properties could lead to a favorable redistribution of blood flow to deprived tissue.6 Nitroglycerine 2% ointment is a relatively inexpensive medication and has been a safe and well tolerated therapy. Common side effects include hypotension and headaches, which are associated with thoracic application. It is our hope that controlled studies will be designed to evaluate the efficacy of nitroglycerine 2% ointment therapy for peripheral neuropathy since diabetic-neuropathic deterioration is a widespread and, as yet, treatment-refractory condition.