Painful peripheral neuropathies treatments

Kemper CA, Kent G et al (1998) Mexiletine for HIV-infected patients with painful peripheral neuropathy a double-blind, placebo-controUed, crossover treatment trial. J Acquir Immune Defic Syndr Hum Retrovirol 19(4) 367-372... 

Adverse reactions occurring in at least 3% of treatment-experienced and treatment-naive patients include the following abdominal pain, abnormal dreams, anorexia, asthenia, back pain, chest pain, depression, diarrhea, dizziness, dyspepsia, fever, flatulence, headache, insomnia, myalgia, nausea, pain, peripheral neuropathy, pneumonia, rash event, sweating, vomiting, weight loss. 

Vincristine, a vinca-alkaloid, prevents proliferation of tumor cells through the inhibition of tubulin polymerization. Vincristine is used as an anticancer agent for leukemia and lymphoma (Himes etal, 1976 Owellen etal., 1976). Clinical use of vincristine is often limited by its adverse effects, which include painful peripheral neuropathy (i.e., neuropathic pain) (Casey et al., 1973 Sandler et al., 1969). Elucidation of the detailed mechanism of neuropathic pain caused by vincristine is needed to improve quality-of-life for patients, and to make vincristine more tolerable for cancer treatment. 

The uses and adverse effects of antiepileptic drugs in the treatment of painful peripheral neuropathy have been reviewed (2). 

Abrams et al. (2003) reported the effects of smoked cannabis in painful peripheral neuropathy secondary to human immunodeficiency virus (HIV) and/or antiretroviral treatment. In a preliminary uncontrolled pilot study (in preparation for a planned placebo-controlled trial) excellent correlation was reported between cannabis dosing and pain improvement, with 10 of 16 participants experiencing a greater than 30% reduction in pain. These results provide the ethical justification to proceed with the controlled trial. 

The phenotype and clinical presentation of antiretroviral toxic neuropathy (ATN) are similar to those of HIV-associated DSP. However, ATN is more likely to be painful, and has an abrupt onset and rapid progression. The main diagnostic clue is the temporal relationship of peripheral neuropathy to the start of NRTI therapy and stabilization, or at least the partial resolution when therapy is interrupted (Moyle and Sadler 1998). ATN most often develops after a mean of 16 to 20 weeks of treatment, unless there are other conditions that lower the threshold. Symptomatic improvement over weeks to months has been reported in two thirds of patients after discontinuation of the offending drug, but may be preceded by an initial period of worsening symptoms, also known as coasting (Berger et al. 1993). Despite the improvement, most patients do not return to a completely asymptomatic state (Hoke and Comblath 2004). 

Peripheral neuropathy is the most common complication reported in type 2 DM. This complication generally presents as pain, tingling, or numbness in the extremities. The feet are affected more often than the hands and fingers. A number of treatment options have been tried with mixed success. Current options include pregabalin, gabapentin, low-dose tricyclic antidepressants, duloxetine, venlafaxine, topiramate, non-steroidal anti-inflammatory drugs, and topical capsaicin. 

Unlabeled Uses Treatment of bipolar disorder, chronic pain, diabetic peripheral neuropathy, essential tremor, hot flashes, hyperhidrosis, migraines, psychiatric disorders (social phobia)... 

Pregabalin is approved for the adjunctive treatment of partial seizures, with or without secondary generalization controlled clinical trials have documented its effectiveness. It is available only in oral form, and the daily dose ranges from 150 to 600 mg/d, usually in two or three divided administrations. Pregabalin is also approved for use in neuropathic pain, including painful diabetic peripheral neuropathy and postherpetic neuralgia. 

First and only treatment currently approved for neuropathic pain associated with diabetic peripheral neuropathy... 

Nifurtimox is a nitrofuran derivative. Adverse effects include anorexia, nausea, vomiting, gastric pain, insomnia, headache, vertigo, excitability, myalgia, arthralgia and convulsions. Peripheral neuropathy may necessitate stopping treatment. 

The incidence of peripheral neuropathy, with sjmmetrical painful paresthesia of the hands and feet often accompanied by sensory loss in the legs, seems to vary with the condition that is being treated, and ranges from under 1% in patients with leprosy to over 70% in patients with prurigo nodularis (41,52). The symptoms do not correlate with either the duration of treatment or the dose. Women and elderly people seem to have an increased risk of neuropathy (53). 

Both formulations of alprostadil are considered more invasive than VEDs or phosphodiesterase inhibitors. For this reason, intracavernosal alprostadil is generally prescribed after patients fail to respond to or cannot use the less invasive interventions. Intracavernosal alprostadil is preferred over intraurethral alprostadil because the former is more effective than the latter. Also, intracavernosal alprostadil may be preferred in patients with diabetes mellitus, who are accustomed to injectable drug therapy and may suffer from peripheral neuropathies, which decreases the patient s perception of pain upon injection. Intraurethral alprostadil is generally reserved as a treatment of last resort for patients who fail other less invasive and more effective forms of therapy and also refuse surgery. 

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