scholarly journals Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons

Pain ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 166-173 ◽  
Author(s):  
Ichiro Harasawa ◽  
Joshua P. Johansen ◽  
Howard L. Fields ◽  
Frank Porreca ◽  
Ian D. Meng
Neuroscience ◽  
2005 ◽  
Vol 132 (2) ◽  
pp. 239-244 ◽  
Author(s):  
S. Marinelli ◽  
M. Connor ◽  
S.A. Schnell ◽  
M.J. Christie ◽  
M.W. Wessendorf ◽  
...  

2011 ◽  
Vol 106 (2) ◽  
pp. 731-740 ◽  
Author(s):  
Nigel P. Pedersen ◽  
Christopher W. Vaughan ◽  
MacDonald J. Christie

The rostral ventromedial medulla (RVM) is an important site of opioid actions and forms part of an analgesic pathway that projects to the spinal cord. The neuronal mechanisms by which opioids act within this brain region remain unclear, particularly in relation to the neurotransmitters GABA and serotonin. In the present study, we examined serotonergic and GABAergic immunoreactivity, identified using immunohistochemistry for tryptophan hydroxylase (TPH) and glutamate decarboxylase (GAD), in combination with in vitro whole cell patch clamping to investigate the role of opioids on the mouse RVM with identified projections to the spinal cord. Tyr-d-Ala-Gly- N-Me-Phe-Gly-ol enkephalin (DAMGO) produced μ-opioid receptor-mediated outward currents in virtually all TPH-immunoreactive projecting neurons and GAD-immunoreactive nonprojecting neurons (87% and 86%). The other groups of RVM neurons displayed mixed responsiveness to DAMGO (40–68%). Deltorphin II and U-69593 produced δ- and κ-opioid receptor-mediated outward currents in smaller subpopulations of RVM neurons, with many of the δ-opioid responders forming a subpopulation of μ-opioid-sensitive GABAergic nonprojecting neurons. These findings are consistent with prior electrophysiological and anatomic studies in the rat RVM and indicate that both serotonergic and GABAergic RVM neurons mediate the actions of μ-opioids. Specifically, μ-opioids have a direct postsynaptic inhibitory influence over both GABAergic and serotonergic neurons, including those that project to the dorsal spinal cord.


2006 ◽  
Vol 96 (6) ◽  
pp. 3465-3473 ◽  
Author(s):  
Clayton W. Winkler ◽  
Sam M. Hermes ◽  
Charles I. Chavkin ◽  
Carrie T. Drake ◽  
Shaun F. Morrison ◽  
...  

This study combines functional and anatomical characterization of neurons in the rostral ventromedial medulla (RVM) to show distinct neurochemical phenotypes between functional classes of neurons. The RVM contains three functional classes of neurons: off cells show a pause in spontaneous activity prior to a nociceptive withdrawal reflex; on cell activity increases prior to a nociceptive reflex; and neutral cell activity does not change significantly during the nociceptive reflex. We determined if serotonin, glutamate decarboxylase (GAD67), or the kappa opioid receptor (KOR) were differentially located within these cell types as predicted by previous studies. In this study, RVM neurons were recorded extracellularly, functionally characterized, and juxtacellularly labeled with biotinamide. Fixed sections were processed for detection of biotinamide and immunfluorescence either for serotonin or for KOR and GAD67. In the first study, serotonin was found exclusively in a subset of neutral cells (33%). These data substantiate previous findings that serotonin is found in some neutral cells whose role in nociception remains unclear. In the second study, we found KOR immunoreactivity in most off (86%) and neutral (80%) cells but rarely in on (13%) cells. We also found GAD67 immunoreactivity in most off (93%) and neutral cells (80%) but less frequently in on cells (63%). Most KOR-immunoreactive cells (16 of 17) also contained GAD67 immunoreactivity regardless of cell classification. These findings support the hypothesis that KOR agonists directly inhibit off and neutral cell activity. The majority of the off and neutral cells are GABAergic, and some on cells are also GABAergic.


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