Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Neuropathic pain is a common feature of many peripheral neuropathies including those associated with diabetes, uremia, HIV infection, and alcohol abuse. Pain is also present in the majority of patients with idiopathic sensory and sensorimotor polyneuropathies. A growing number of pharmacologic agents are available for the treatment of neuropathic pain. The medications that have undergone the most rigorous study are the tricyclic antidepressants and anticonvulsants. These two families of medications are widely used and represent first-line agents in the management of neuropathic pain. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, as directed therapy may help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, as adverse events are not uncommon for some of the medications. Treatment of neuropathic pain remains challenging, with considerable variability in an individual's response to the various agents and even to different drugs in the same class. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain.
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PMID:Painful Peripheral Neuropathy. 1193 24

Neuropathic pain can develop as an agonizing sequela of diabetes mellitus and chronic uremia. A chemical link between both conditions of altered metabolism is the highly reactive compound methylglyoxal (MG), which accumulates in all cells, in particular neurons, and leaks into plasma as an index of the severity of the disorder. The electrophilic structure of this cytotoxic ketoaldehyde suggests TRPA1, a receptor channel deeply involved in inflammatory and neuropathic pain, as a molecular target. We demonstrate that extracellularly applied MG accesses specific intracellular binding sites of TRPA1, activating inward currents and calcium influx in transfected cells and sensory neurons, slowing conduction velocity in unmyelinated peripheral nerve fibers, and stimulating release of proinflammatory neuropeptides from and action potential firing in cutaneous nociceptors. Using a model peptide of the N terminus of human TRPA1, we demonstrate the formation of disulfide bonds based on MG-induced modification of cysteines as a novel mechanism. In conclusion, MG is proposed to be a candidate metabolite that causes neuropathic pain in metabolic disorders and thus is a promising target for medicinal chemistry.
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PMID:Methylglyoxal activates nociceptors through transient receptor potential channel A1 (TRPA1): a possible mechanism of metabolic neuropathies. 2274 Jun 98