Abstract
The rostroventromedial medulla (RVM) is an important area of the endogenous pain-regulating
system, in which 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) are
2 main transmitters involved in pain modulation. However, whether 5-HT and GABA are
colocalized is poorly understood. By using glutamate decarboxylase 67-green fluorescence
protein (GAD67-GFP) knock-in mouse, we confirmed the colocalization of 5-HT and GABA
in the RVM, with a main distribution in the raphe magnus nucleus and paragigantocellular
reticular nucleus. Interestingly, more than half (51.6%) of the 5-HT/GABA-immunoreactive
(ir) neurons expressed neurokinin-1 receptors (NK-1R) and one-third (30.1%) of the
5-HT/GABA/NK-1R-ir neurons projected to the spinal cord, suggesting that substance
P (SP) should regulate the activity of 5-HT/GABA-ir spinal cord-projecting neurons.
By combining retrograde and anterograde tracing methods, we observed that the cuneiform
nucleus, dorsal raphe nucleus, and lateral periaqueductal gray are the main origin
nuclei for the SP-ir fibers and terminals in the RVM. Finally, after formalin injection
into the mice hind paw, 29.2% SP-ir RVM-projecting neurons from supra-RVM nuclei and
33.1% NK-1R-ir spinal cord-projecting neurons in the RVM were activated. The present
study provides potent morphological evidence that 5-HT and GABA are coexistent in
RVM-spinal cord-projecting neurons that are also regulated by SPergic projections.
Perspective
The results will greatly enhance our understanding for the modulation of nociceptive
information in the descending pain-regulating system.
Key words
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Article info
Publication history
Published online: May 13, 2013
Accepted:
February 6,
2013
Received in revised form:
November 24,
2012
Received:
August 14,
2012
Footnotes
Supported by National Natural Science Foundation of China (Nos. 30800590, 30971123, 31010103909).
The authors declare that they have no conflict of interests.
Chen and Wang contributed equally to this work.
Identification
Copyright
© 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.
