 |
 Previous Article | Next Article 
The Journal of Neuroscience, July 15, 2001, 21(14):5281-5288
Inhibition of Neuropathic Pain by Selective Ablation of Brainstem
Medullary Cells Expressing the µ-Opioid Receptor
Frank
Porreca1,
Shannon
E.
Burgess1,
Luis R.
Gardell1,
Todd W.
Vanderah1,
T. Philip
Malan Jr1,
Michael H.
Ossipov1,
Douglas A.
Lappi2, and
Josephine
Lai1
1 Departments of Pharmacology and Anesthesiology,
University of Arizona, Tucson, Arizona 85724, and
2 Advanced Targeting Systems, San Diego, California 92121
Neurons in the rostroventromedial medulla (RVM) project to spinal
loci where the neurons inhibit or facilitate pain transmission. Abnormal activity of facilitatory processes may thus represent a
mechanism of chronic pain. This possibility and the phenotype of RVM
cells that might underlie experimental neuropathic pain were
investigated. Cells expressing µ-opioid receptors were targeted with
a single microinjection of saporin conjugated to the µ-opioid agonist
dermorphin; unconjugated saporin and dermorphin were used as controls.
RVM dermorphin-saporin, but not dermorphin or saporin, significantly
decreased cells expressing µ-opioid receptor transcript. RVM
dermorphin, saporin, or dermorphin-saporin did not change baseline
hindpaw sensitivity to non-noxious or noxious stimuli. Spinal nerve
ligation (SNL) injury in rats pretreated with RVM dermorphin-saporin
failed to elicit the expected increase in sensitivity to non-noxious
mechanical or noxious thermal stimuli applied to the paw. RVM
dermorphin or saporin did not alter SNL-induced experimental pain, and
no pretreatment affected the responses of sham-operated groups. This
protective effect of dermorphin-saporin against SNL-induced pain was
blocked by  -funaltrexamine, a selective µ-opioid receptor antagonist, indicating specific interaction of dermorphin-saporin with
the µ-opioid receptor. RVM microinjection of dermorphin-saporin, but
not of dermorphin or saporin, in animals previously undergoing SNL
showed a time-related reversal of the SNL-induced experimental pain to
preinjury baseline levels. Thus, loss of RVM µ receptor-expressing cells both prevents and reverses experimental neuropathic pain. The
data support the hypothesis that inappropriate tonic-descending facilitation may underlie some chronic pain states and offer new possibilities for the design of therapeutic strategies.
Key words:
neuropathic pain; descending facilitation; RVM; µ-opioid receptors; saporin; ON cells
Copyright © 2001 Society for Neuroscience 0270-6474/01/21145281-08$05.00/0
This article has been cited by other articles:
|
|
|
|
 
B. L. Whitsel, O. V. Favorov, Y. Li, M. Quibrera, and M. Tommerdahl
Area 3a Neuron Response to Skin Nociceptor Afferent Drive
Cereb Cortex,
June 4, 2008;
(2008)
bhn086v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. H. Kline IV and R. G. Wiley
Spinal {micro}-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception
J. Neurosci.,
January 23, 2008;
28(4):
904 - 913.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. M. Hellman, T. S. Brink, and P. Mason
Activity of Murine Raphe Magnus Cells Predicts Tachypnea and On-Going Nociceptive Responsiveness
J Neurophysiol,
December 1, 2007;
98(6):
3121 - 3133.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. Carlson, J. J. Maire, M. E. Martenson, and M. M. Heinricher
Sensitization of Pain-Modulating Neurons in the Rostral Ventromedial Medulla after Peripheral Nerve Injury
J. Neurosci.,
November 28, 2007;
27(48):
13222 - 13231.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Benoliel, J. Epstein, E. Eliav, R. Jurevic, and S. Elad
Orofacial Pain in Cancer: Part I--Mechanisms
J. Dent. Res.,
June 1, 2007;
86(6):
491 - 505.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Kincaid, M. J. Neubert, M. Xu, C. J. Kim, and M. M. Heinricher
Role for Medullary Pain Facilitating Neurons in Secondary Thermal Hyperalgesia
J Neurophysiol,
January 1, 2006;
95(1):
33 - 41.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Mason
DECONSTRUCTING ENDOGENOUS PAIN MODULATIONS
J Neurophysiol,
September 1, 2005;
94(3):
1659 - 1663.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y.-P. Chen, S.-R. Chen, and H.-L. Pan
Systemic Morphine Inhibits Dorsal Horn Projection Neurons through Spinal Cholinergic System Independent of Descending Pathways
J. Pharmacol. Exp. Ther.,
August 1, 2005;
314(2):
611 - 617.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. D. Meng, J. P. Johansen, I. Harasawa, and H. L. Fields
Kappa Opioids Inhibit Physiologically Identified Medullary Pain Modulating Neurons and Reduce Morphine Antinociception
J Neurophysiol,
March 1, 2005;
93(3):
1138 - 1144.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Khasabov, J. R. Ghilardi, P. W. Mantyh, and D. A. Simone
Spinal Neurons That Express NK-1 Receptors Modulate Descending Controls That Project Through the Dorsolateral Funiculus
J Neurophysiol,
February 1, 2005;
93(2):
998 - 1006.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Heinricher and M. J. Neubert
Neural Basis for the Hyperalgesic Action of Cholecystokinin in the Rostral Ventromedial Medulla
J Neurophysiol,
October 1, 2004;
92(4):
1982 - 1989.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. S. Brink and P. Mason
Role for Raphe Magnus Neuronal Responses in the Behavioral Reactions to Colorectal Distension
J Neurophysiol,
October 1, 2004;
92(4):
2302 - 2311.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. R. Gardell, T. W. Vanderah, S. E. Gardell, R. Wang, M. H. Ossipov, J. Lai, and F. Porreca
Enhanced Evoked Excitatory Transmitter Release in Experimental Neuropathy Requires Descending Facilitation
J. Neurosci.,
September 10, 2003;
23(23):
8370 - 8379.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Bie, H. L. Fields, J. T. Williams, and Z. Z. Pan
Roles of {alpha}1- and {alpha}2-Adrenoceptors in the Nucleus Raphe Magnus in Opioid Analgesia and Opioid Abstinence-Induced Hyperalgesia
J. Neurosci.,
August 27, 2003;
23(21):
7950 - 7957.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Bie and Z. Z. Pan
Presynaptic Mechanism for Anti-Analgesic and Anti-Hyperalgesic Actions of {kappa}-Opioid Receptors
J. Neurosci.,
August 13, 2003;
23(19):
7262 - 7268.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Foo and P. Mason
Discharge of Raphe Magnus ON and OFF Cells Is Predictive of the Motor Facilitation Evoked by Repeated Laser Stimulation
J. Neurosci.,
March 1, 2003;
23(5):
1933 - 1940.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. S. Gold, D. Weinreich, C.-S. Kim, R. Wang, J. Treanor, F. Porreca, and J. Lai
Redistribution of NaV1.8 in Uninjured Axons Enables Neuropathic Pain
J. Neurosci.,
January 1, 2003;
23(1):
158 - 166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Marinelli, C. W. Vaughan, S. A. Schnell, M. W. Wessendorf, and M. J. Christie
Rostral Ventromedial Medulla Neurons That Project to the Spinal Cord Express Multiple Opioid Receptor Phenotypes
J. Neurosci.,
December 15, 2002;
22(24):
10847 - 10855.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Zhuo and G. F. Gebhart
Modulation of Noxious and Non-Noxious Spinal Mechanical Transmission From the Rostral Medial Medulla in the Rat
J Neurophysiol,
December 1, 2002;
88(6):
2928 - 2941.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. G. Khasabov, S. D. Rogers, J. R. Ghilardi, C. M. Peters, P. W. Mantyh, and D. A. Simone
Spinal Neurons that Possess the Substance P Receptor Are Required for the Development of Central Sensitization
J. Neurosci.,
October 15, 2002;
22(20):
9086 - 9098.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. E. Burgess, L. R. Gardell, M. H. Ossipov, T. P. Malan Jr, T. W. Vanderah, J. Lai, and F. Porreca
Time-Dependent Descending Facilitation from the Rostral Ventromedial Medulla Maintains, But Does Not Initiate, Neuropathic Pain
J. Neurosci.,
June 15, 2002;
22(12):
5129 - 5136.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
