Painful peripheral neuropathies

Joseph EK, Chen X et al (2004) Novel mechanism of enhanced nociception in a model of AIDS therapy-induced painful peripheral neuropathy in the rat. Pain 107(1-2) 147-158 Jubelt B, Berger JR (2001) Does viral disease underlie ALS Lessons from the AIDS pandemic. Neurology 57(6) 945-946... 

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... 

Vinblastine -vinca alkaloid inhibits tubulin polymerization G2 phase specific -bone marrow suppression -vesicant if extravasated -nausea and vomiting -constipation (often secondary to neuropathy induced ileus) -neuropathy (jaw pain, peripheral neuropathy, autonomic neuropathy) -SIADH -tumor pain... 

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. 

Dizziness, loss of taste, nausea, vomiting, stomach pain, peripheral neuropathy or numbness in fingers, toes, face Rare (less than 1 %)... 

In a study of painful peripheral neuropathy, CP99.994 (< 100 pg/kg i.v., over 2 h) had no analgesic effect (Suarez et al., 1994). Thus, to date clinical studies indicate that NK1 receptor antagonists are unlikely to be general analgesics (Rupniak and Kramer, 1999). 

Suarez, G. A., Opfer-Gehrking, T. L., McLean, D. B., Low, P. A. Double-blind, placebo-controlled study of the efficacy of substance P (NK1) receptor antagonist in painful peripheral neuropathy, Neurology 1994, 44, 373P. 

Paclitaxel Taxol Carcinoma of the breast, ovaries Kaposi sarcoma nonsmall cell lung cancer Blood disorders (anemia, leukopenia, neutropenia, thrombocytopenia] hypersensitivity reaction (skin rash/itching, shortness of breath] joint/muscle pain peripheral neuropathies Gl distress (nausea, vomiting, diarrhea]... 

Bortezomib (Velcade] Multiple myeloma Blood disorders (anemia, neutropenia, thrombocytopenia] dyspnea joint and muscle pain peripheral neuropathies... 

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. 

Flatters, S. J., and Bennett, G. J. (2004). Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy. Pain 109, 150—161. 

Tanner, K. D., Reichling, D. B., and Levine, J. D. (1998). Nociceptor hyper-responsiveness during vincristine-induced painful peripheral neuropathy in the rat. J. Neurosci. 18, 6480-6491. 

Xiao, W., Boroujerdi, A., Bennett, G. J., and Luo, Z. D. (2007). Chemotherapy-evoked painful peripheral neuropathy Analgesic effects of gabapentin and effects on expression of the alpha-2-delta type-1 calcium channel subunit. Neuroscience 144, 714—720. 

This trial provides the first clinical evidence that blockade of NK ] receptors results in analgesia in man. The dose used in the earlier study of painful peripheral neuropathy was considerably lower than the dose used in this trial, raising the possibility that the result was a false negative and that the outcome may have been different had higher doses been administered. 

These include postherpetic neuralgia, phantom limb pain, peripheral neuropathies of various causes, central pain, e.g. following a stroke, compression neuropathies, and the complex regional pain syndromes (comprising causalgia, when there is nerve damage, and reflex sympathetic dystrophy, when there is tissue but no nerve injury) they present the most challenging problems. 

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

Mexiletine has been used to treat painful peripheral neuropathy in patients with HIV infection, without any evidence of efficacy (15,16). In one study of 22 patients, nine had adverse effects probably related to mexiletine, including nausea in five, vomiting in four, and abdominal pain, diarrhea, dizziness, insomnia, rises in liver enzymes, and skin rash in one patient each (15). Adverse effects in seven patients required dosage reduction in four cases and withdrawal in three (because of a rash in one case and gastrointestinal effects in two). 

In a study in which 48 patients with painful peripheral neuropathy due to HIV iufectiou were treated with mexiletiue, 10 had uausea aud vomitiug that required dosage modificatiou dosage modificatiou was also occasioued by dizziuess iu oue case aud uriuary reteutiou iu three cases (16). 

Kajander KC, Bennett GJ 1992 Onset of a painful peripheral neuropathy in rat A partial and differential deafferentation and spontaneous discharge in A and AA primary afferent neurons. J Neurophysiol 68 734-744... 

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. 

Neurological Sensory loss 1-2 weeks postexposure, paresthesias, painful peripheral neuropathy, headache, weakness, encephalopathy... 

Malaise and abdominal pain Peripheral neuropathy and muscular weakness ii. Skin changes (hyperpigmentation and dermatitis) v. Mees lines transverse bands on the fingemniln d. Complications squamous cell carcinoma of jhe-skin and lung 4. Lead poisoning (plumbism)... 

ACUTE HEALTH RISKS gastrointestinal disturbances nausea vomiting diarrhea abdominal pain peripheral neuropathy. 

Ren K, Thomas D A, Dubner R (1995). Nerve growth factor alleviates a painful peripheral neuropathy in rats. Brain Res. 699 286-292. 

B. Chronic effects include painful peripheral neuropathy, myopathy, chorea, stomatitis, and ophthalmoplegia. Hair loss and nail dystrophy (Mees lines) may appear after 2-4 weeks. 

Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies loss of epidermal innervation and activation of Langerhans cells. Exp Neurol 2006 201 507-514. 

In an open study, 30 children, who had been treated for solid tumors and leukemia and had developed a painful peripheral neuropathy, were given pregabalin 150-300 mg/day for 8 weeks [263 ]. There was significant long-lasting pain relief in 25 them. There were mild or moderate adverse effects nausea and drowsiness in the titration phase) in four patients drug withdrawal was not required. 

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