• Porreca F, Burgess SE, Gardell LR, Vanderah TW, Malan TP, Jr., Ossipov MH, Lappi DA and Lai J (2001). Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the µ-opioid receptor. J Neurosci. 21 (14): 5281-8. Summary: Neurons in the rostroventromedial medulla (RVM) project to spinal loci where the neurons inhibit or facilitate pain transmission. Abnormal activity of facilitatory processes may thus represent a mechanism of chronic pain. This possibility and the phenotype of RVM cells that might underlie experimental neuropathic pain were investigated. Cells expressing &mgr;-opioid receptors were targeted with a single microinjection of saporin conjugated to the &mgr;-opioid agonist dermorphin; unconjugated saporin and dermorphin were used as controls. RVM dermorphin-saporin, but not dermorphin or saporin, significantly decreased cells expressing &mgr;-opioid receptor transcript. RVM dermorphin, saporin, or dermorphin-saporin did not change baseline hindpaw sensitivity to non-noxious or noxious stimuli. Spinal nerve ligation (SNL) injury in rats pretreated with RVM dermorphin-saporin failed to elicit the expected increase in sensitivity to non-noxious mechanical or noxious thermal stimuli applied to the paw. RVM dermorphin or saporin did not alter SNL-induced experimental pain, and no pretreatment affected the responses of sham-operated groups. This protective effect of dermorphin-saporin against SNL-induced pain was blocked by beta-funaltrexamine, a selective &mgr;-opioid receptor antagonist, indicating specific interaction of dermorphin-saporin with the &mgr;-opioid receptor. RVM microinjection of dermorphin-saporin, but not of dermorphin or saporin, in animals previously undergoing SNL showed a time-related reversal of the SNL-induced experimental pain to preinjury baseline levels. Thus, loss of RVM &mgr; receptor-expressing cells both prevents and reverses experimental neuropathic pain. The data support the hypothesis that inappropriate tonic-descending facilitation may underlie some chronic pain states and offer new possibilities for the design of therapeutic strategies. <http://www.jneurosci.org/cgi/content/full/21/14/5281
http://www.jneurosci.org/cgi/content...act/21/14/5281
http://www.ncbi.nlm.nih.gov/entrez/q...uids=11438603> Departments of Pharmacology and Anesthesiology, University of Arizona, Tucson, Arizona 85724, USA. frankp@u.arizona.edu

[This message was edited by Wise Young on November 28, 2001 at 08:51 AM.]