Neonatal cystitis alters mechanisms of stress-induced visceral hypersensitivity in rats. (1st May 2022)

• Record Type: Journal Article
• Authors: Ness, Timothy J.; DeWitte, Cary; Robbins, Meredith T.; DeBerry, Jennifer J.
• Is Part Of: Neuroscience letters. Volume 778(2022)
• Publication Date: 2022-05-01
• Subjects: AUC Area-Under-the-Curve -- AFS acute footshock -- NBI neonatal bladder inflammation -- IC/BPS interstitial cystitis/bladder pain syndrome -- IP intraperitoneal -- IT intrathecal -- NMDA N-methyl-D-aspartate -- VMR visceromotor response; Bladder -- Interstitial cystitis -- Visceral pain; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2022.136617
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Acute footshock stress augments visceromotor responses to urinary bladder sensation. The NMDA antagonist MK-801 given IT suppresses the facilitatory effects of acute footshock. Stress-induced inhibition of paw withdrawal reflexes is not present in rats which experienced neonatal bladder inflammation. Neonatal bladder inflammation results in a failure of an opioidergic inhibitory system activated by acute stress. Abstract: In rodent models, conditioning with acute footshock (AFS) has been demonstrated to produce bladder hypersensitivity which is more robust when rats, tested as adults, had also been pretreated with neonatal bladder inflammation (NBI). The spinal neurochemical mechanisms of pro-nociceptive processes in rats pretreated with NBI are not fully known and so the present study administered intrathecal (IT) opioid (naloxone) and NMDA receptor (MK-801) antagonists to determine whether these receptors' actions had been altered by NBI. Female Sprague-Dawley rat pups were intravesically pretreated on postnatal days P14-P16 with a 1% zymosan solution or with control procedures and then raised to adulthood (12–15 weeks of age). Bladder hypersensitivity was induced through use of an AFS paradigm. Visceromotor responses (VMRs; abdominal muscle contractions) to graded, air pressure-controlled urinary bladder distension were used as nociceptive endpoints. Immediately following AFS pretreatments, rats were anesthetized and surgically prepared. Pharmacological antagonists were administered via an IT catheter onto the lumbosacral spinal cord and VMRs determined 15 min later. Administration of IT naloxone hydrochloride (10 μg) to rats which had been pretreated only with AFS resulted in VMRs that were more robust than VMRs in similarly pretreated rats that received IT normal saline. In contrast, IT naloxone had no significant effect on rats that had been pretreated with both NBI&AFS, although MK-801 was inhibitory. These effects of IT naloxone suggest the presence of inhibitory influences in normal rats that are absent in rats pretreated with NBI. Absence of inhibitory influences produced by AFS was also demonstrated in rats pretreated with NBI&AFS using measures of thermal paw withdrawal latency (PWL): rats pretreated with only AFS had longer PWLs than rats pretreated with both NBI&AFS. Together, a reduction in anti-nociceptive mechanisms coupled with pro-nociceptive NMDA-linked mechanisms results in more robust nociceptive responses to distension in rats which had experienced NBI.