Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the μ-opioid receptor

Frank Porreca, Shannon E. Burgess, Luis R. Gardell, Todd W. Vanderah, T. Philip Malan, Michael H. Ossipov, Douglas A. Lappi, Josephine Lai

Research output: Contribution to journalArticlepeer-review

219 Scopus citations


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 μ-opioid receptors were targeted with a single microinjection of saporin conjugated to the μ-opioid agonist dermorphin; unconjugated saporin and dermorphin were used as controls. RVM dermorphin-saporin, but not dermorphin or saporin, significantly decreased cells expressing μ-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 β-funaltrexamine, a selective μ-opioid receptor antagonist, indicating specific interaction of dermorphin-saporin with the μ-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 μ 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.

Original languageEnglish (US)
Pages (from-to)5281-5288
Number of pages8
JournalJournal of Neuroscience
Issue number14
StatePublished - Jul 15 2001


  • Descending facilitation
  • Neuropathic
  • Neuropathic pain
  • ON cells
  • RVM
  • Saporin
  • μ-opioid receptors

ASJC Scopus subject areas

  • Neuroscience(all)


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