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The Journal of Neuroscience, November 1, 2000, 20(21):8131-8137
Antagonism of the Melanocortin System Reduces Cold and Mechanical
Allodynia in Mononeuropathic Rats
Dorien H.
Vrinten1, 2,
Willem Hendrik
Gispen1,
Gerbrand J.
Groen2, and
Roger A. H.
Adan1
Departments of 1 Medical Pharmacology and
2 Anesthesiology, Rudolf Magnus Institute for
Neurosciences, University Medical Centre Utrecht, 3584 CG Utrecht, The
Netherlands
The presence of both pro-opiomelanocortin-derived peptides and
melanocortin (MC) receptors in nociception-associated areas in the
spinal cord suggests that, at the spinal level, the MC system might be
involved in nociceptive transmission. In the present study, we
demonstrate that a chronic constriction injury (CCI) to the rat sciatic
nerve, a lesion that produces neuropathic pain, results in changes in
the spinal cord MC system, as shown by an increased binding of
125I-NDP-MSH to the dorsal horn. Furthermore, we
investigated whether intrathecal administration (in the cisterna magna)
of selective MC receptor ligands can affect the mechanical and cold
allodynia associated with the CCI. Mechanical and cold allodynia were
assessed by measuring withdrawal responses of the affected limb to von Frey filaments and withdrawal latencies upon immersion in a 4.5°C water bath, respectively. We show that treatment with the MC receptor antagonist SHU9119 has a profound anti-allodynic effect, suggesting that the endogenous MC system has a tonic effect on nociception. In
contrast, administration of the MC4 receptor agonists MTII and
D-Tyr-MTII primarily increases the sensitivity to
mechanical and cold stimulation. No antinociceptive action was observed
after administration of the selective MC3 receptor agonist Nle- -MSH. Together, our data suggest that the spinal cord MC system is involved in neuropathic pain and that the effects of MC receptor ligands on the
responses to painful stimuli are exerted through the MC4 receptor. In
conclusion, antagonism of the spinal melanocortin system might provide
a new approach in the treatment of neuropathic pain.
Key words:
neuropathic pain; chronic constriction injury; allodynia; melanocortins; melanocortin-4 receptor; spinal cord; dorsal horn; in situ 125I-NDP-MSH binding
Copyright © 2000 Society for Neuroscience 0270-6474/00/20218131-07$05.00/0
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