Rat model of attention-deficit hyperactivity disorder exhibits delayed recovery from acute incisional pain due to impaired descending noradrenergic inhibition

Chronic pain and attention-deficit hyperactivity disorder (ADHD) frequently coexist. However, the common pathology is still unclear. Attenuated noradrenergic endogenous analgesia can produce acute pain chronification, and dysfunction of noradrenergic systems in the nervous system is relevant to ADHD...

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Published in:Scientific reports 2023-04, Vol.13 (1), p.5526-5526, Article 5526
Main Authors: Suto, Takashi, Kato, Daiki, Koibuchi, Ikuya, Arai, Yuki, Ohta, Jo, Hiroki, Tadanao, Obata, Hideaki, Saito, Shigeru
Format: Article
Language:English
Subjects:
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Acute Pain
Adrenergic receptors
Analgesia
Animals
Attention Deficit Disorder with Hyperactivity - drug therapy
Attention deficit hyperactivity disorder
Chronic pain
Humanities and Social Sciences
Hyperactivity
Hypersensitivity
Immunohistochemistry
Locus coeruleus
Microdialysis
multidisciplinary
Nervous system
Norepinephrine
Pain
Pain perception
Rats
Rats, Inbred SHR
Rats, Sprague-Dawley
Science
Science (multidisciplinary)
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Summary:Chronic pain and attention-deficit hyperactivity disorder (ADHD) frequently coexist. However, the common pathology is still unclear. Attenuated noradrenergic endogenous analgesia can produce acute pain chronification, and dysfunction of noradrenergic systems in the nervous system is relevant to ADHD symptoms. Noxious stimuli-induced analgesia (NSIA) is measured to estimate noradrenergic endogenous analgesia in spontaneously hypertensive rats (SHR) as an ADHD model and control. Recovery of pain-related behaviors after paw incision was assessed. Contributions of noradrenergic systems were examined by in vivo microdialysis and immunohistochemistry. The SHR showed attenuated NSIA and needed a more extended period for recovery from acute pain. These results suggest ADHD patients exhibit acute pain chronification due to pre-existing attenuated noradrenergic endogenous analgesia. Immunohistochemistry suggests abnormal noradrenaline turnover and downregulation of the target receptor (alpha2a adrenoceptor). Standard ADHD treatment with atomoxetine restored NSIA and shortened the duration of hypersensitivity after the surgery in the SHR. NSIA protocol activated the locus coeruleus, the origin of spinal noradrenaline, of both strains, but only the control exhibited an increase in spinal noradrenaline. This result suggests dysfunction in the noradrenaline-releasing process and can be recognized as a novel mechanism of attenuation of noradrenergic endogenous analgesia.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-023-32512-9