precede the diagnosis of diabetes, or not occur for many years. In addition to
the above sensory symptoms, motor nerves (weakness) and autonomic nerves
(sweat, fainting, and impotence) may also be involved. Both type I and type II

diabetes can lead to this disorder. Incidence ranges from 20-50% of the time. The condition can become severe enough to affect gait, and lead to the need for amputation.

The axon fibers and their insulating (myelin) sheath may be affected, with a both being involved most frequently. On nerve testing, the nerves may be slow, and their response diminished. The damage is a result of vascular and metabolic problems.

Microangiopathy and the resultant impaired oxygen delivery to the nerves is one source of damage. The small vessels feeding the nerves tend towards endothelium-induced vasoconstriction and blockage of the normal nitric oxide vasodilatation response. Hyperviscosity of the blood and platelet aggregation can add to the vascular damage to the nerves.

Metabolic factors are a greater component of diabetic neuropathy. Sorbitol (elevated in diabetics) and other polyols accumulate in the nerves, damaging supporting glial elements of the nerve and allowing axons in the nerve to develop excessive sodium. This diminishes the normal sodium/potassium gradient that allows the axons to conduct electricity, and axonal function is impaired. Changes in the nerves’ energy stores are secondary results. Na/K ATPase and protein kinase C are affected, these enzymes provide the necessary energy to establish electrolyte gradients necessary for nerve condution. Polyol and glucose buildup also leads to the development of free radicals which, along with depleted antioxidant defenses may induce further oxidative stress on the nerves. The mitochondria suffer oxidative stress as well. Insulin is a neuronal growth factor, and its decrease in diabetes reduces the nerves’ ability to recover from metabolic and ischemic injury.

Treatment of diabetic neuropathy is difficult and often frustrating. Optimal control of the diabetes is the best direct approach. Aldose reductase inhibitors aimed at decreasing nerve accumulation of sorbitol, and other approaches to the mechanism of damage have not proven successful. Because approaches to achieve a reversal of the diabetic damage are not available, medications that modulate the intensity of the painful signals have proven useful. Narcotic analgesics are generally poor at decreasing the quality of neuropathic pain (stabbing, burning, pins and needles), but can affect the intensity. Tramadol, and oxycontin have Level I evidence to support their use, but complications of narcotics can be prohibitive. Several antiepileptic medications have Level I evidence supporting their use. Gabapentin, and pregabalin (Lyrica) are effective; some find lamotrigine, sodium valproate, topiramate, and oxcarbamazepine to provide relief. Each of these have a different mechanism of< action, but help control the abnormal excitability of the sensory nerves, or help modulate the signal as it is transmitted in the spinal cord and brain. Serotonin and norepinephrine uptake inhibitors are used as antidepressants, but several also have a role in controlling neuropathic pain. Duloxetine (Cymbalta), imipramine, amitryptiline, mexilitine, and venlaxafine all have some support in the literature as being effective. Sometimes a combination can be used to benefit from multiple mechanisms of action. Compounding pharmacies can make a crème with several of these chemicals for use on the feet; this provides some relief with minimal systemic side effects.

Because this is a common condition, clinical trials are frequently ongoing to test new treatments. NervePro has conducted clinical trials for this condition for over 14 years, and helped bring several new medications to market. Ask the NervePro staff if there are any programs that would be appropriate for you.