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)

Prediabetes is associated with a length-dependent polyneuropathy that typically is sensory predominant and painful. A diagnosis of prediabetes should be sought in patients with otherwise idiopathic sensory-predominant neuropathy by doing a 2-hour oral glucose tolerance test. Fasting plasma glucose of 100 to 125 mg/dL or 2-hour glucose 140 to 199 mg/dL (impaired glucose tolerance) constitutes prediabetes. Most patients with neuropathy associated with prediabetes (NAP) are obese and show metabolic manifestations of insulin resistance, including hyperlipidemia and hypertension. Appropriate treatment addresses hyperglycemia, insulin resistance, and neuropathic pain. Professionally administered individualized diet and exercise counseling (modeled on the Diabetes Prevention Program) has been shown to be more effective than glucose-lowering medications in preventing progression from impaired glucose tolerance to diabetes, and is the mainstay of treatment for all patients with NAP. The goals of this therapy should be a 5% to 7% reduction in weight and an increase to 30 minutes of moderate exercise five times weekly. Patients with prediabetes are at increased risk for myocardial infarction, stroke, and peripheral vascular disease. Therefore, risk reduction with control of hypertension and hyperlipidemia is essential. Neuropathic pain troubles nearly every patient with NAP, and often limits aerobic exercise. No trials have specifically addressed the patient population with NAP, and neuropathic pain treatment closely follows recommendations for diabetic neuropathy. Gabapentin, lamotrigine, and tricyclic antidepressants are well-validated first-line therapies. Adjunctive therapy with opioids, nonsteroidal anti-inflammatory drugs often are necessary. Diet and exercise seem to reduce neuropathic pain in patients with NAP.
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PMID:Polyneuropathy with Impaired Glucose Tolerance: Implications for Diagnosis and Therapy. 1561 Jul 5

Protein tyrosine phosphatase 1B (PTP1B) has been shown to dephosphorylate and inactivate insulin receptors, which contributes to the pathogenesis of diabetes. Neuropathic pain is one of the severe complications that results from diabetic neuropathy. However, whether PTP1B was involved in the development of diabetic neuropathic pain is largely unknown. The current study illustrated that PTP1B was located in spinal cord dorsal horn neurons of Sprague-Dawley rats. Western blot analysis demonstrated that the diabetic neuropathic pain induced by intraperitoneal injection of streptozotocin was associated with an increased protein expression and a dynamic redistribution of spinal PTP1B into excitatory glutamatergic synapses. We found that PTP1B operated to stimulate Src kinase and enhance the tyrosine phosphorylation of N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. The siRNA-mediated knockdown of PTP1B in streptozotocin-injected rats repressed Src activity, decreased NMDA receptor phosphorylation and alleviated the thermal hyperalgesia and mechanical allodynia. A similar analgesia against diabetic neuropathic pain was also achieved when PTP1B activity was manipulated by a chemical PTP Inhibitor or PTP1B(C215S) mutant. These data revealed a regulated expression of PTP1B in spinal cord dorsal horn of rats after diabetic neuropathy, and demonstrated that inhibition of PTP1B was beneficial for the treatment of pain hypersensitivity related to diabetes.
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PMID:Inhibition of protein tyrosine phosphatase 1B in spinal cord dorsal horn of rats attenuated diabetic neuropathic pain. 2952 16