Painful diabetic neuropathy

Duloxetine, a dual inhibitor of serotonin and norepinephrine reuptake indicated for depression and painful diabetic neuropathy, is expected to become first-line therapy for SUI. Duloxetine is thought to facilitate the bladder-to-sympathetic reflex pathway, increasing urethral and external urethral sphincter muscle tone during the storage phase. 

In addition to treating MDD [51-53], duloxetine was approved as the first agent for the treatment of painful diabetic neuropathy in the U.S. [54-56]. It also has been used for stress urinary incontinence in women in Europe [57,58]. In 2007, duloxetine was approved for the treatment of generalized anxiety disorder in the U.S. 

Temporary relief of pain from rheumatoid arthritis, osteoarthritis, and relief of neuralgias such as the pain following shingles (herpes zoster) or painful diabetic neuropathy. 

Geriatric Considerations - Summary Compared to placebo, duloxetine is effective for the treatent of depression and painful diabetic neuropathy Few head-to-head studies are available comparing duloxetine to other agents in the treatment of depression or painful neuropathy. Because this agent may increase urethral sphincter activity, it is now being assessed as an agent for the treatment of stress urinary incontinence. This same property may increase the risk of urinary retention, although this has not been well documented. Duloxetine has not been well studied with respect to falls. 

Goldstein DJ, Lu Y, Detke MJ, et al. Duloxetine vs. placebo in patients with painful diabetic neuropathy. Pain 2005 16 109-118. 

Zeigler, D., Lynch, S. A., Muir, J., Benjamin, J., Max, M. B. Transdermal clonidine versus placebo in painful diabetic neuropathy, Pain 1992, 48, 403-408. 

In fact, carbamazepine is recommended as the drug of first choice in the treatment of trigeminal neuralgia. Results from clinical trials have been positive in the treatment of painful diabetic neuropathy (Rull et al., 1969 Wilton, 1974 Gomez-Perez et al., 1996). After 4 weeks treatment with carbamazepine, central pain after stroke was improved only in five out of 14 patients (Leijon and Boivie, 1989). Carbamazepine was found to be effective for migraine prophylaxis (Rompel and Bauermeister,... 

Dejgard, A., Petersen, P., Kastrup, J Mexilitine for treatment of chronic painful diabetic neuropathy, Lancet 1988, 1, 9-11. 

Jarvis, B. and Coukell, A. J. Mexilitine. A review of its therapeutic use in painful diabetic neuropathy. 

Ross, D.R. and Varipapa, R.J. Treatment of painful diabetic neuropathy with topical capsaicin, New Engl. J. Med. 1989, 321, 474-475. 

The Capsaicin Study Group Treatment of painful diabetic neuropathy with topical capsaicin a multicenter, double-blind, vehicle-controlled study, Arch. Intern. Med. 1991, 151, 2225-2229. 

Nelson K. A., Park K. M., Robinovitz E., Tsigos C., and Max M. B. (1997). High-dose oral dextromethorphan versus placebo in painful diabetic neuropathy and postherpetic neuralgia. Neurology 48 1212-1218. 

Watson, C. P., Moulin, D., Watt-Watson,J., Gordon, A., and Eisenhoffer,J. (2003). Controlled-release oxycodone relieves neuropathic pain A randomized controlled trial in painful diabetic neuropathy. Pain 105, 71-78. 

Atli A, Dogra S (2005) Zonisamide in the treatment of painful diabetic neuropathy a randomized, double-blind, placebo-controlled pilot study. Pain Med 6 225-234... 

TCAs ANTIDIABETIC DRUGS Likely to impair control of diabetes. TCAs may t serum glucose levels by up to 150%, t appetite (particularly carbohydrate craving) and i metabolic rate Be aware and monitor blood sugar weekly until stable. Generally considered safe unless diabetes is poorly controlled or is associated with significant cardiac or renal disease. Amitriptyline, imipramine and citalopram are also used to treat painful diabetic neuropathy... 

Politsky JM. Painful diabetic neuropathy treatment with modern anticonvulsants. Mature Med Can 2000 3 60-3. 

Sang CN, Booher S, Gilron I, Parada S, Max MB. Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia efficacy and dose-response trials. Anesthesiology 2002 96(5) 1053-61. 

Nelson KA, Park KM, RobinovitzE, et al. High-dose dextromethorphan versus placebo in painful diabetic neuropathy. Neurology 1997 48 1212— 1218. 

Neuropathic pain is severe chronic pain due to damage to sensory nerves. This is not because of tissue injury and can occur as a consequence of central nervous system disorders, such as stroke or multiple sclerosis, or because of malignancy, amputation (phantom limb pain) diabetic neuropathy or following infection with Herpes zoster (as shingles). Mechanisms underlying neuropathic pain are poorly understood. The pain is described as... 

Capsaicin interacts with the canilloid receptor (VRl) on sensory afferents. VRl is a gated cation channel of the TRP family, modulated by a variety of noxious stimuli. Chronic exposure to capsaicin stimulates and desensitizes this channel. Capsaicin also causes local depletion of substance P, an endogenous neuropeptide involved in sensory perception and pain transmission. Capsaicin is available as a 0.025% cream (Zostrix, others) and 0.075% aeam (Zostrix HP, others) to be applied three to four times daily. Capsaicin is FDA approved for the treatment of postherpetic neuralgia and painful diabetic neuropathy, although its efficacy in relieving pain is debatable. 

Winkler G, Pal B, Nagybeganyi E, Ory I, Porochnavec M, Kempler P. Effectiveness of different benfotiamine dosage regimens in the treatment of painful diabetic neuropathy. Arzneimittefforschung 1999 49 220-224. 

With these reservations in mind, the frequency of symptomatic neuropathy seems to be 15-20% in unselected diabetes patient populations, whereas the frequency of more or less pronounced abnormalities in the peripheral nervous system varies between 20% and 50%, depending on the methodology applied. The prevalence in type 2 diabetes seems to be higher than in type 1 diabetic patients although data are somewhat contradictory [11]. At the onset of diabetes the frequency of nervous system abnormalities is 5-10%, increasing linearly as a function of duration of diabetes and amounts to 50% of the population after 25 years duration of diabetes. Ten to twenty per cent of patients with peripheral diabetic neuropathy will have painful diabetic neuropathy that requires treatment. 

A. Tricyclic antidepressants are among the widest studied drugs for treatment of painful diabetic neuropathy. It has a documented effect in these patients and meta-analysis has shown a 50% reduction in pain intensity in 30% of patients with diabetic neuropathic pain [28]. Effects are probably due to an inhibition of both 5 HT, norepinephrine and serotonin presynaptic reuptake. Sodium and calcium channel blockade and... 

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