Unpredictable sound stress induces a novel form of hyperalgesic priming

Dionéia Araldi; Paul G Green; Jon D Levine

doi:10.1097/j.pain.0000000000003950

Back

Unpredictable sound stress induces a novel form of hyperalgesic priming

Journal article

Peer reviewed

Unpredictable sound stress induces a novel form of hyperalgesic priming

Dionéia Araldi, Paul G Green and Jon D Levine

Pain (Amsterdam), Vol.167(6), pp.1381-1390

06/2026

DOI: 10.1097/j.pain.0000000000003950

PMID: 41841955

View Online

Abstract

Unpredictable stress induces long-lasting nociceptor plasticity, enhancing and prolonging pain, contributing to chronic pain. To enhance our understanding of how unpredictable stress induces pronociceptive neuroplasticity, we investigated its effect on nociceptor function, testing the hypothesis that unpredictable sound stress (SS) induces hyperalgesic priming, a model of acute to chronic pain transition. Male rats were subjected to intense amplitude (20-110 dB) unpredictable sound, 5- or 10-second tones presented every minute, at random times, for 30 minutes, on days 1, 3, and 4. On day 18, prostaglandin E 2 (PGE 2 ) was administered intradermally. In both sham and SS groups, PGE 2 induces hyperalgesia, measured at 30 minutes postinjection. However, only in the SS group was PGE 2 hyperalgesia still present at 4 hours, indicative of hyperalgesic priming. Agents known to inhibit the expression and maintenance of type I priming, inhibitors of protein kinase C epsilon, and peripheral protein translation, respectively, did not affect the SS-induced prolongation of PGE 2 -induced hyperalgesia. In contrast, a protein kinase A (PKA) inhibitor attenuated the prolongation of PGE 2 -induced hyperalgesia. This inhibition remained, unattenuated, when evaluated 1 month after administration of the PKA inhibitor, compatible with PKA contributing to both expression and maintenance of SS-induced hyperalgesic priming. The effect of combined Src and mitogen-activated protein kinase inhibitors, which fully reverses type II priming, also inhibited SS-induced priming; however, this effect diminished over time. Our findings support a novel form of hyperalgesic priming induced by SS. Insights into the mechanisms underlying SS-induced priming could inform targeted interventions for pain syndromes influenced by stress.

Animals

Dinoprostone - toxicity

Disease Models, Animal

Hyperalgesia - chemically induced

Hyperalgesia - etiology

Hyperalgesia - physiopathology

Male

Pain Measurement

Rats

Rats, Sprague-Dawley

Sound - adverse effects

Stress, Psychological - complications

Stress, Psychological - etiology

Stress, Psychological - physiopathology

Details

Title: Subtitle: Unpredictable sound stress induces a novel form of hyperalgesic priming
Creators: Dionéia Araldi - University of Iowa
Paul G Green - University of California, San Francisco
Jon D Levine - University of California, San Francisco
Resource Type: Journal article
Publication Details: Pain (Amsterdam), Vol.167(6), pp.1381-1390
DOI: 10.1097/j.pain.0000000000003950
PMID: 41841955
ISSN: 0304-3959
eISSN: 1872-6623
Grant note: R21 AG086905 / NIA NIH HHS NS084545 / NINDS NIH HHS AG086905 / NIA NIH HHS
Language: English
Date published: 06/2026
Academic Unit: Neuroscience and Pharmacology
Record Identifier: 9985178668402771

Metrics

1 Record Views