Chronic neuropathic pain, caused by lesions in the peripheral or central nervous system, comes in many forms. We describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms. Randomized controlled clinical trials of gabapentin, the 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants provide an evidence-based approach to the treatment of neuropathic pain, and specific recommendations are presented for use of these medications. Continued progress in basic and clinical research on the pathophysiologic mechanisms of neuropathic pain may make it possible to predict effective treatments for individual patients by application of a pain mechanism-based approach.

Using degenerate oligonucleotide probes encoding conserved regions of the γ-aminobutyric acid/norepinephrine transporter gene family, we have cloned a rat brain cDNA encoding a creatine transporter (rCREAT). rCREAT encodes a highly hydrophobic, 635-amino-acid protein possessing 12 potential transmembrane domains and canonical sites for N-linked glycosylation and protein phosphorylation. Transfection of rCREAT cDNA into mammalian cells results in the expression of [¹⁴C]creatine uptake, which is blocked by low micromolar concentrations of recognized creatine uptake inhibitors. Two rCREAT mRNAs are expressed in the rat brain, retina, kidney and heart. Whole-brain rCREAT mRNAs demonstrate a marked postnatal rise to steady-state adult levels. In situ hybridization studies indicate a widespread, differential rCREAT mRNA expression in adult rat brain, with high expression noted over myelinated fiber tracts, cerebellar granule cells, hippocampal pyramidal cells, brainstem nuclei and endothelial cells of the choroid plexus. These studies will allow the development of new molecular probes useful for defining the creatine transporter's cellular expression pattern, function in ATP homeostasis and association with disorders of cellular energy metabolism.

No abstract