Abstract |
Endothelin-1 (ET-1) applied to the sciatic nerve or injected into the plantar hindpaw of rats induces pain behavior (ipsilateral hindpaw flinching) and selective excitation of nociceptors by activation of endothelin-A (ET(A)) receptors. To determine the pharmacological profile of the sensory fibers that mediate this pain behavior, we administered lidocaine (LID, a non-selective conduction blocker) or tetrodotoxin (TTX) prior to ET-1. LID (1 or 2%, 0.1 ml) was injected percutaneously into the sciatic notch, or TTX (10 microM, 4 microl) was injected into the sciatic nerve prior to the more distal application of ET-1 (400 microM, 40 microl) onto the sciatic nerve or subcutaneously into the plantar hindpaw (400 microM, 10 microl). LID inhibited ET-1-induced flinching in a dose-dependent manner; the mean total number of flinches was reduced by 39% for 1% LID and by 87% for 2% LID. In contrast, TTX failed to inhibit flinching behavior induced by sciatic nerve application of ET-1 despite a similar magnitude of motor and sensory blockade as that observed with 2% LID. Partial blockade of flinching behavior by intraneural TTX (mean total flinches were reduced by 51%) was observed after subcutaneous injection of ET-1. Unexpectedly, ET-1 prolonged the actions of 1% LID and, even when applied alone, produced clear signs of motor and sensory conduction block. These results are evidence that ET-1-induced pain is transmitted to the central nervous system via sensory fibers using tetrodotoxin-resistant sodium channels, and that ET-1 has analgesic actions that exist despite the activation of local pain pathways.
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Authors | Constance S Houck, Alla Khodorova, Amy M Reale, Gary R Strichartz, Gudarz Davar |
Journal | Pain
(Pain)
Vol. 110
Issue 3
Pg. 719-726
(Aug 2004)
ISSN: 0304-3959 [Print] United States |
PMID | 15288413
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Endothelin-1
- Tetrodotoxin
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Topics |
- Animals
- Dose-Response Relationship, Drug
- Endothelin-1
(toxicity)
- Male
- Neurons, Afferent
(drug effects, physiology)
- Pain
(chemically induced, physiopathology)
- Pain Measurement
(drug effects, methods)
- Rats
- Rats, Sprague-Dawley
- Sciatic Nerve
(drug effects, physiology)
- Tetrodotoxin
(toxicity)
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