Spinal neurochemical mechanisms of acute stress-induced visceral hypersensitivity in healthy rats.
Footshock
Rat
Stress
Urinary bladder
Visceral hyperalgesia
Journal
Neuroscience letters
ISSN: 1872-7972
Titre abrégé: Neurosci Lett
Pays: Ireland
ID NLM: 7600130
Informations de publication
Date de publication:
23 01 2022
23 01 2022
Historique:
received:
13
11
2021
revised:
11
12
2021
accepted:
13
12
2021
pubmed:
21
12
2021
medline:
16
3
2022
entrez:
20
12
2021
Statut:
ppublish
Résumé
Psychological stress has been demonstrated to increase reports of pain in humans with pelvic pain of urologic origin. In rodent models, conditioning with acute footshock (AFS) has been demonstrated to increase measures of stress/anxiety as well as bladder hypersensitivity. The spinal neurochemical mechanisms of this pro-nociceptive process are unknown and so the present study administered antagonists for multiple receptors that have been associated with facilitatory mechanisms into the spinal intrathecal space. Bladder hypersensitivity was induced through use of an AFS paradigm in which female Sprague-Dawley rats received a 15-min intermittent shock treatment. Visceromotor responses (VMRs; abdominal muscle contractions) to air pressure-controlled urinary bladder distension (UBD) were used as nociceptive endpoints. Immediately following AFS treatments, rats were anesthetized (inhaled isoflurane, IP urethane) and surgically prepared. Pharmacological antagonists were administered via an intrathecal (IT) catheter onto the lumbosacral spinal cord and VMRs to graded UBD determined 15 min later. Administration of IT naloxone hydrochloride (10 μg) and IT phentolamine hydrochloride (10 μg) resulted in VMRs that were more robust than VMRs in rats that received AFS and IT normal saline whereas there was no significant effect of these drugs on VMRs in rats which underwent non-footshock procedures. In contrast, a low dose of the NMDA-receptor antagonist, MK-801 (30 μg), significantly reduced VMRs in rats made hypersensitive to UBD by AFS, but had no significant effect on rats that underwent non-footshock procedures. This study suggests that pro-nociceptive effects of AFS in otherwise healthy rats involve a spinal NMDA-linked mechanism. The effects of IT naloxone and IT phentolamine suggest the presence of inhibitory influences that are opioidergic and/or alpha-adrenergic and that are masked by the pro-nociceptive mechanisms. Other agents with no statistically significant effect on VMRs include methysergide (30 μg), ondansetron (10 μg), mecamylamine (50 μg), antalarmin (24 μg), aSVG30 (12 μg), and SSR149415 (50 μg).
Identifiants
pubmed: 34929317
pii: S0304-3940(21)00780-1
doi: 10.1016/j.neulet.2021.136401
pmc: PMC8810671
mid: NIHMS1766162
pii:
doi:
Substances chimiques
Excitatory Amino Acid Antagonists
0
Receptors, N-Methyl-D-Aspartate
0
Dizocilpine Maleate
6LR8C1B66Q
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
136401Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK051413
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK082315
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier B.V. All rights reserved.
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