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Transient inflammation-induced ongoing pain is driven by TRPV1 sensitive afferents
Alec Okun1, Milena DeFelice, Nathan Eyde
1Department of Pharmacology, College of Medicine, University of Arizona, Tucson, AZ 85724, USA.
Molecular Pain
|January 12, 2011
Summary
Inflammation causes transient ongoing pain and persistent hypersensitivity, driven by TRPV1-positive fibers. Understanding these early post-injury mechanisms can lead to new pain relief strategies.
Area of Science:
- Neuroscience
- Pain Research
- Pharmacology
Background:
- Tissue injury causes both hypersensitivity to stimuli and ongoing, spontaneous pain.
- Previous work showed pain relief acts as a reward in nerve-injured rats.
- This study investigates inflammation-induced ongoing pain's temporal and mechanistic features.
Purpose of the Study:
- To differentiate the time course and mechanisms of ongoing pain versus evoked hypersensitivity after inflammation.
- To identify the specific nerve fibers and receptors involved in inflammation-induced ongoing pain.
Main Methods:
- Complete Freund's Adjuvant (CFA) induced inflammation in rats.
- Assessed thermal hyperalgesia, guarding behavior, and conditioned place preference (CPP).
- Utilized spinal clonidine, peripheral lidocaine nerve block, resiniferatoxin (RTX), and a TRPV1 antagonist (AMG9810).
Main Results:
- CFA induced thermal hyperalgesia and guarding behavior, persisting for at least 4 days.
- Spinal clonidine produced CPP 1 day post-CFA but not 4 days, while blocking hyperalgesia at both times.
- Peripheral lidocaine blocked ongoing pain, indicating afferent fiber involvement.
- RTX blocked hyperalgesia, ongoing pain, and guarding behavior, implicating TRPV1-positive fibers.
- TRPV1 antagonism (AMG9810) reversed hyperalgesia but not ongoing pain or guarding.
Conclusions:
- Inflammation causes distinct transient ongoing pain and persistent evoked hypersensitivity.
- Ongoing pain is mediated by peripheral input from TRPV1-positive fibers.
- TRPV1 receptor antagonism does not alleviate ongoing pain.
- Investigating afferent fiber excitation mechanisms offers novel pain relief strategies.
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