Roles of α1- and α2-adrenoceptors in the nucleus raphe magnus in opioid analgesia and opioid abstinence-induced hyperalgesia

B. Bie, H. L. Fields, J. T. Williams, Z. Z. Pan

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Noradrenaline and α-adrenoceptors have been implicated in the modulation of pain in various behavioral conditions. Noradrenergic neurons and synaptic inputs are present in neuronal circuits critical for pain modulation, but their actions on neurons in those circuits and consequently the mechanisms underlying noradrenergic modulation of pain remain unclear. In this study, both recordings in vitro and behavioral analyses in vivo were used to examine cellular and behavioral actions mediated by α1- and α2-adrenoceptors on neurons in the nucleus raphe magnus. We found that α1- and α2-receptors were colocalized in the majority of a class of neurons (primary cells) that inhibit spinal pain transmission and are excited during opioid analgesia. Activation of the α1-receptor depolarized whereas α 2-receptor activation hyperpolarized these neurons through a decrease and an increase, respectively, in potassium conductance. Blockade of the excitatory α1-receptor or activation of the inhibitory α2-receptor significantly attenuated the analgesia induced by local opioid application, suggesting that α1-receptor-mediated synaptic inputs in these primary cells contribute to their excitation during opioid analgesia. In the other cell class (secondary cells) that is thought to facilitate spinal nociception and is inhibited by analgesic opioids, only α1-receptors were present. Blocking the α 1-receptor in these cells significantly reduced the hyperalgesia (increased pain) induced by opioid abstinence. Thus, state-dependent activation of α1-mediated synaptic inputs onto functionally distinct populations of medullary pain-modulating neurons contributes to opioid-induced analgesia and opioid withdrawal-induced hyperalgesia.

Original languageEnglish (US)
Pages (from-to)7950-7957
Number of pages8
JournalJournal of Neuroscience
Issue number21
StatePublished - Aug 27 2003


  • Analgesia
  • Hyperalgesia
  • Nucleus raphe magnus
  • Opioid
  • Pain
  • α-adrenoceptors
  • α-adrenoceptors

ASJC Scopus subject areas

  • Neuroscience(all)


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