Kappa Opioid Receptor (KOR) and GAD67 Immunoreactivity Are Found in off and neutral Cells in the Rostral Ventromedial Medulla

2006 ◽  
Vol 96 (6) ◽  
pp. 3465-3473 ◽  
Author(s):  
Clayton W. Winkler ◽  
Sam M. Hermes ◽  
Charles I. Chavkin ◽  
Carrie T. Drake ◽  
Shaun F. Morrison ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Cell Activity ◽  
Cell Types ◽  
Kappa Opioid Receptor ◽  
Rostral Ventromedial Medulla ◽  
Kappa Opioid ◽  
Nociceptive Reflex ◽  
Ventromedial Medulla ◽  
Functional Classes

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.

scholarly journals Cloning and pharmacological characterization of a rat kappa opioid receptor.

1993 ◽  
Vol 90 (21) ◽  
pp. 9954-9958 ◽  
Author(s):  
F. Meng ◽  
G. X. Xie ◽  
R. C. Thompson ◽  
A. Mansour ◽  
A. Goldstein ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Pharmacological Characterization

scholarly journals Characterization of kappa opioid receptor mediated, dynorphin-stimulated [35S]GTPγS binding in mouse striatum for the evaluation of selective KOR ligands in an endogenous setting

2015 ◽  
Vol 99 ◽  
pp. 131-141 ◽  
Author(s):  
Lei Zhou ◽  
Edward L. Stahl ◽  
Kimberly M. Lovell ◽  
Kevin J. Frankowski ◽  
Thomas E. Prisinzano ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Mouse Striatum ◽  
Gtpγs Binding

Pharmacological Characterization of Kappa Opioid Receptor Agonists

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Sophia Kaska ◽  
Lindsay Kornberger ◽  
Andrew Biggerstaff ◽  
Bronwyn Kivell ◽  
Thomas Prisinzano
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Pharmacological Characterization ◽  
Receptor Agonists ◽  
Opioid Receptor Agonists

Pharmacological characterization of the cloned kappa opioid receptor as a kappa1b subtype

Neuroreport ◽  
1994 ◽  
Vol 5 (16) ◽  
pp. 2161-2164 ◽  
Author(s):  
Josephine Lai ◽  
Shou-wu Ma ◽  
Rong-Huan Zhu ◽  
Richard B. Rothman ◽  
Klaus-Ulrich Lentes ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid ◽  
Pharmacological Characterization

scholarly journals Construction and characterization of a kappa opioid receptor devoid of all free cysteines

2004 ◽  
Vol 17 (1) ◽  
pp. 37-48 ◽  
Author(s):  
David Ott ◽  
Renato Frischknecht ◽  
Andreas Plückthun
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Kappa Opioid

scholarly journals Kappa opioids inhibit the GABA/glycine terminals of rostral ventromedial medulla projections in the superficial dorsal horn of the spinal cord

2021 ◽  
Author(s):  
Yo Otsu ◽  
Karin Aubrey
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Kappa Opioid Receptor ◽  
Rostral Ventromedial Medulla ◽  
Projection Neurons ◽  
Superficial Dorsal Horn ◽  
Opioid Receptor Agonist ◽  
Ventromedial Medulla

Background and Purpose: Descending projections from neurons in the rostral ventromedial medulla (RVM) make synapses within the superficial dorsal horn of the spinal cord that are involved in acute nociception and the development of chronic pain and itch. In addition, this projection plays an important role in mediating the analgesic effects of opioids. However, our knowledge about the spinal synaptic targets of RVM projections and their modulation by opioids is unknown. Experimental Approach: We used ex vivo optogenetic stimulation of RVM descending fibres and whole-cell patch-clamp recordings from superficial dorsal horn (SDH) neurons to identify the target neurons and to investigate their descending synaptic inputs. Key Results: We demonstrate that SDH neurons are targeted by descending GABA/glycine inhibitory inputs from the RVM, although glycinergic inputs predominate. These SDH neurons had diverse morphological and electrical properties. This inhibitory synapse was presynaptically suppressed by the kappa opioid receptor agonist U69593. By contrast, the mu-opioid receptor agonist DAMGO inhibited only a subset of RVM-SDH synapses, acting both pre- and postsynaptically, while the delta-opioid receptor agonist deltorphin II had little effect. Conclusion and Implications: Developing reliable and effective alternatives to opioid analgesics requires a detailed, mechanistic understanding of how opioids interact with nociceptive circuits. This study selectively and systematically characterises the synaptic connections between RVM projection neurons and their SDH targets to advance our knowledge of how this descending projection is organised and modulated. In addition, it improves our understanding of how opioids alter spinal pathways involved in the sensations of pain and itch.

Kappa Opioids Inhibit Physiologically Identified Medullary Pain Modulating Neurons and Reduce Morphine Antinociception

2005 ◽  
Vol 93 (3) ◽  
pp. 1138-1144 ◽  
Author(s):  
I. D. Meng ◽  
J. P. Johansen ◽  
I. Harasawa ◽  
H. L. Fields
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Rostral Ventromedial Medulla ◽  
Tail Flick ◽  
Direct Inhibition ◽  
Postsynaptic Inhibition ◽  
Kappa Opioids ◽  
Ventromedial Medulla

Microinjection of kappa opioid receptor (KOR) agonists into the rostral ventromedial medulla (RVM) attenuates mu-opioid receptor mediated antinociception and stress-induced analgesia, yet is also reported to have an analgesic effect. To determine how KOR agonists produce both antinociceptive and antianalgesic actions within the RVM, the KOR agonist U69593 was microinjected directly into the RVM while concurrently monitoring tail flick latencies and RVM neuronal activity. Among RVM neurons recorded in vivo, two types show robust changes in activity just prior to the nocifensive tail flick reflex: on cells burst just prior to a tail flick and their activity is pronociceptive, whereas off cells pause just prior to the tail flick and their activity is antinociceptive. Although RVM microinjection of U69593 did not affect tail flick latencies on its own, it did attenuate the on cell burst, an effect blocked by co-injection of the KOR antagonist, nor-binaltorphimine (nor-BNI). Furthermore, U69593 inhibited ongoing activity in subsets of off cells (4/11) and neutral cells (3/9). Microinjection of U69593 into the RVM also attenuated morphine antinociception and suppressed the excitation of off cells. Together with previous in vivo and in vitro studies, these results are consistent with the idea that KOR agonists can be either pronociceptive through direct inhibition of off cells, or antianalgesic through both postsynaptic inhibition and presynaptic inhibition of glutamate inputs to RVM off cells.

New C(2)-sulfonyl ester-type Salvinorin A ligands to the kappa-opioid receptor

Planta Medica ◽  
2015 ◽  
Vol 81 (05) ◽  
Author(s):  
PR Polepally ◽  
A Keasling ◽  
K White ◽  
E Vardy ◽  
BL Roth ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Kappa Opioid Receptor ◽  
Salvinorin A ◽  
Kappa Opioid
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