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The Journal of Neuroscience, July 15, 2001, 21(14):5358-5366
Local Injection of Endothelin-1 Produces Pain-Like Behavior and
Excitation of Nociceptors in Rats
Alexander P.
Gokin1, 2,
Moin U.
Fareed1, 3,
Hui-Lin
Pan4,
Guy
Hans1, 3,
Gary R.
Strichartz2, 3, and
Gudarz
Davar1
1 Molecular Neurobiology of Pain, and
2 Sensory Neurophysiology Laboratories of the Pain Research
Center, Department of Anesthesiology, Perioperative and Pain Medicine,
Brigham and Women's Hospital, Boston, Massachusetts 02115, 3 Department of Biological Chemistry and Molecular
Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, and
4 Department of Anesthesiology, Physiology and
Pharmacology, Wake Forest University School of Medicine, Winston-Salem,
North Carolina 27157
Neurobehavioral and neurophysiological actions of the peptide
endothelin-1 (ET-1) were investigated after subcutaneous plantar hindpaw injections in adult male Sprague Dawley rats. Hindpaw flinching
developed within minutes after ET-1 (8-16 nmol) injection, peaked at
30 min, lasted for 60 min, and was strongly inhibited by the
endothelin-A (ETA) receptor antagonist, BQ-123 (3.2 M). In separate experiments, impulse activity of single,
physiologically characterized sensory C-, A -, and A -fibers was
recorded from the sciatic nerve in anesthetized rats after subcutaneous
injections of endothelin-1 (1-20 nmol), alone or together with BQ-123
(3.2 M), into the plantar hindpaw receptive fields of these
units. All nociceptive C-fibers (31 of 33 C-fibers studied) were
excited by ET-1 (1-20 nmol) in a dose-dependent manner. For doses of
16-20 nmol, the mean latency for afferent activation after injection of ET-1 was 3.16 ± 0.31 min, and the mean and maximum response frequency were 2.02 ± 0.48 impulses (imp)/sec and
14.0 ± 3.2 imp/sec, respectively. All 10 nociceptive A-fibers
(of 12 A-fibers studied) also responded to 1-20 nmol of ET-1 in a
dose-dependent manner with a mean latency of 3.5 ± 0.12 min and
mean response frequency of 3.3 ± 2.3 imp/sec. In contrast, most
A-fibers (9 of 12) did not respond to ET-1. BQ-123, when coinjected
with ET-1, blocked ET-1-induced activation in all C- and A-fibers
tested. These data demonstrate that subcutaneous administration of ET-1
to the rat plantar hindpaw produces pain-like behavior and selective excitation of nociceptive fibers through activation of ETA receptors.
Key words:
excitability; peripheral nerve; algogenic; C-fiber; nociceptor; cancer
Copyright © 2001 Society for Neuroscience 0270-6474/01/21145358-09$05.00/0
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