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The Journal of Neuroscience, August 15, 1999, 19(16):7175-7181
Pain-Induced Analgesia Mediated by Mesolimbic Reward Circuits
Robert W.
Gear1, 2,
K.
O.
Aley2, and
Jon D.
Levine2, 3, 4, 5, 6
1 Center for Orofacial Pain, Departments of
2 Oral and Maxillofacial Surgery, 3 Anatomy,
and 4 Medicine, 5 Division of Neuroscience,
and 6 National Institutes of Health Pain Center (UCSF),
University of California, San Francisco, California 94143
We tested the hypothesis that noxious stimuli induce pain
modulation by activation of supraspinal structures. We found that intense noxious stimuli (i.e., subdermal injection of capsaicin or paw
immersion in hot water) induced profound attenuation of the jaw-opening
reflex in the anesthetized rat; forepaw subdermal capsaicin also
elevated the mechanical hindpaw-withdrawal threshold in the awake rat.
These antinociceptive effects were blocked by previous injection of
either a dopamine antagonist (flupentixol) or an opioid antagonist
(naloxone) into the nucleus accumbens. Additional experiments in
anesthetized animals showed that the antinociceptive effect of noxious
stimulation by either capsaicin ( 100 µg) or hindpaw immersion in
hot water (45°C for 4 min) correlated with the intensity of the
stimulus. The maximal antinociceptive effect of capsaicin was similar
in magnitude to that of a high dose of morphine (10 mg/kg) injected
subcutaneously. Injection of the GABAA-receptor agonist
muscimol, but not naloxone, into the rostroventral medulla, a
major component of descending pain modulation systems, blocked
capsaicin-induced antinociception. Although it is widely thought that
painful stimuli may induce analgesia by activating forebrain
structures, this is the first demonstration that such a mechanism
exists. Furthermore, this mechanism can be engaged by naturalistic
stimuli in awake animals. These observations imply that painful stimuli
might under certain conditions be rewarding.
Key words:
antinociception; capsaicin; nociception; noxious stimuli; nucleus accumbens; rostroventral medulla; opioids; dopamine; thermal
stimulation; GABA; rats
Copyright © 1999 Society for Neuroscience 0270-6474/99/19167175-07$05.00/0
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