Endomorphin-2-immunoreactive fibers selectively appose serotonergic neuronal somata in the rostral ventral medial medulla

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


The rostral portion of the ventral medial medulla (RVM) is a crucial site for the supraspinal antinociceptive actions of opioids. Previous studies have reported that serotonergic antagonists block the analgesia induced by microinjection of morphine into the RVM (Hammond and Yaksh [1984] Brain Res 298:329-337) and that spinally projecting serotonergic RVM neurons express μ-opioid receptors (MOR) (Kalyuzhny et al. [1996] J Neurosci 16:6490-6503; Wang and Wessendorf [1999] J Comp Neurol 404:183-196). In addition, axons immunoreactive for the endogenous MOR ligand endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) (EM-2) have been reported to be in the RVM (Martin-Schild et al. [1999] J Comp Neurol 405:450-471; Pierce and Wessendorf [2000] J Chem Neuroanat 18:181-207). In the present study we examined the relationship of EM-2-immunoreactive (EM-2-ir) axons to serotonergic and nonserotonergic RVM neurons in rats, including neurons projecting to the dorsal spinal cord. We also examined the origins of EM-2-ir in the RVM. Using unbiased methods we estimated the total number of cells in the RVM to be 1.50 × 104 and of these up to 70% were retrogradely labeled from the dorsal spinal cord. EM-2-ir fibers apposed both serotonergic and nonserotonergic RVM neuronal profiles. However, serotonergic profiles were significantly more likely to be apposed than nonserotonergic profiles. Thus, although serotonergic neurons comprise a minority of RVM neurons (23% of the total RVM neurons), they appear to be selectively apposed by EM-2-ir fibers. We also found that hypothalamic EM-2-ir neurons, but not EM-2-ir neurons, in the nucleus of the solitary tract projected their axons to the RVM.

Original languageEnglish (US)
Pages (from-to)701-713
Number of pages13
JournalJournal of Comparative Neurology
Issue number5
StatePublished - Jun 10 2007


  • Analgesia
  • Hypothalamus
  • Spinal cord
  • μ-opioid receptor


Dive into the research topics of 'Endomorphin-2-immunoreactive fibers selectively appose serotonergic neuronal somata in the rostral ventral medial medulla'. Together they form a unique fingerprint.

Cite this