Neonatal bladder inflammation induces long-term visceral pain and altered responses of spinal neurons in adult rats. Neuroscience 2017 Mar 27;346:349-364
Date
01/28/2017Pubmed ID
28126369Pubmed Central ID
PMC5337157DOI
10.1016/j.neuroscience.2017.01.021Scopus ID
2-s2.0-85012926870 (requires institutional sign-in at Scopus site) 17 CitationsAbstract
Painful events early in life have been shown to increase the incidence of interstitial cystitis/painful bladder syndrome in adulthood. However, the intrinsic mechanism is not well studied. We previously reported that neonatal bladder inflammation causes chronic visceral hypersensitivity along with molecular disruption of spinal GABAergic system in rats. The present study investigates whether these molecular changes affect the integrative function and responses of bladder-sensitive primary afferent and spinal neurons. Neonatal bladder inflammation was induced by intravesicular injection of zymosan during postnatal (P) days 14-16. In adulthood (P60), the viscero-motor response (VMR) to visceral stimuli was significantly inhibited by intrathecal (i.t) HZ166 (GABAAα-2 agonist) only in neonatally saline-treated, but not in neonatally zymosan-treated rats. HZ166 significantly inhibited the responses of bladder-responsive lumbosacral (LS) spinal neurons to urinary bladder distension (UBD) and slow infusion (SI) in neonatally saline-treated rats. Similar results were also observed in naïve adult rats where HZ166 produced significant inhibition of bladder-responsive spinal neurons. However, HZ166 did not inhibit responses of UBD-responsive spinal neurons from neonatally zymosan-treated rats. The drug did not attenuate the responses of UBD-sensitive pelvic nerve afferent (PNA) fibers to UBD and SI in either group of rats tested. Immunohistochemical studies showed a significantly lower level of GABAAα-2 receptor expression in the LS spinal cord of neonatally zymosan-treated rats compared to saline-treated rats. These findings indicate that neonatal bladder inflammation leads to functional and molecular alteration of spinal GABAAα-2 receptor subtypes, which may result in chronic visceral hyperalgesia in adulthood.
Author List
Kannampalli P, Babygirija R, Zhang J, Poe MM, Li G, Cook JM, Shaker R, Banerjee B, Sengupta JNAuthors
James M. Cook PhD University Distinguished Professor in the Chemistry and Biochemistry department at University of Wisconsin - MilwaukeeJyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
Reza Shaker MD Assoc Provost, Sr Assoc Dean, Ctr Dir, Chief, Prof in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAnimals, Newborn
Benzodiazepines
Colon
Cystitis, Interstitial
Female
GABA-A Receptor Agonists
Imidazoles
Lumbosacral Region
Neurons
Rats
Rats, Sprague-Dawley
Receptors, GABA-A
Spinal Cord
Urinary Bladder
Visceral Pain
Zymosan