Acute bladder inflammation differentially affects rat spinal visceral nociceptive neurons

doi:10.1016/j.neulet.2009.10.027

Neuroscience Letters

Volume 467, Issue 2, 25 December 2009, Pages 150-154

https://doi.org/10.1016/j.neulet.2009.10.027 Get rights and content

Abstract

The present investigation examined the effect of inflammation produced by intravesical zymosan on spinal dorsal horn neuronal responses to urinary bladder distension (UBD). Extracellular single-unit recordings of neurons excited by UBD were obtained in spinalized female Sprague–Dawley rats. Neurons were classified as Type I—inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II—not inhibited by a HNCS. In Experiment 1—following neuronal characterization, 1% zymosan was infused into the bladder and after 2 h spinal units were recharacterized. Control rats received intravesical saline or subcutaneous zymosan. In Experiment 2—rats were pretreated with intravesical zymosan 24 h prior to surgical preparation. Control rats received anesthesia only. 137 spinal dorsal horn neurons excited by UBD were characterized. In comparison with controls, Type II neurons demonstrated increased spontaneous and UBD-evoked activity following intravesical zymosan treatment (both Experiments 1 and 2) whereas Type I neurons demonstrated either no change (Experiment 1) or decreased activity (Experiment 2) following bladder inflammation. No significant changes were noted in neuronal activity in control experiments. Inflammation differentially affects subpopulations of spinal dorsal horn neurons excited by UBD that can be differentiated according to the effect of HNCS. This results in an altered pattern of spinal sensory transmission that may serve as the mechanism for the generation of visceral nociception.

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Acknowledgements

Technical assistance of T. Uzzell and R. Cannon is gratefully acknowledged. Supported by DK51413 and DK 078655.

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We have previously demonstrated that both discrete Visceromotor Response measures and AUC statistics are normally distributed (Ness et al, 2021). These studies were performed using the same methods as we have previously reported (Ness and Castroman, 2001; Ness et al, 2009, Ness and Randich, 2010). Briefly, animals were anesthetized with isoflurane (5%) and a tracheal cannula placed allowing for mechanical ventilation.
Spinal mechanisms associated with visceral hypersensitivity are poorly understood. One model of bladder hypersensitivity with phenotypic features similar to the disorder interstitial cystitis/bladder pain syndrome is the neonatal bladder inflammation (NBI) model. In this model, rat pup bladders are infused with zymosan solutions on post-partum days 14–16 and then rats are retested as adults. Studies of other sites of deep tissue hypersensitivity have suggested a role for corticotropin-releasing factor (CRF) receptors type 1 and 2 (CRFR1 and CRFR2). Using neurochemical measures, pharmacological manipulations and both reflex and neuronal responses to urinary bladder distension as endpoints, the present study probed the role of CRFR2s in bladder hyperalgesia secondary to NBI and acute bladder re-inflammation as an adult (ABI). ELISA measures of the lumbosacral spinal cord demonstrated increased CRFR1s and CRFR2s following pretreatment with both NBI + ABI as well as NBI-related increases in the CRFR2 agonist urocortin 2. Intrathecal CRFR2 antagonists, but not a CRFR1 antagonist, blocked the augmentation of visceromotor responses to distension following pretreatment with both NBI + ABI. Lumbosacral dorsal horn neuronal responses to distension in rats pretreated with NBI + ABI were attenuated by the spinal topical administration of a CRFR2 antagonist. These studies suggest therapeutic value of CRFR2 antagonists in the treatment of painful bladder disorders.
Footshock stress differentially affects responses of two subpopulations of spinal dorsal horn neurons to urinary bladder distension in rats
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Constant-pressure UBD (20–60 mm Hg, 20 s) was the noxious visceral test stimulus employed and was produced by inflating the urinary bladder with air using a 22 gage angiocatheter placed via the urethra and tightly sutured around the distal urethral orifice. UBD was administered as a phasic stimulus (rapid onset, rapid offset) as previously described (Ness et al., 2009). Intravesical distending pressure was monitored via an in-line, low-volume pressure transducer.
This investigation examined the effect of footshock on responses of 283 spinal dorsal horn neurons (DHNs) to urinary bladder distension (UBD). Female rats were treated with seven daily sessions of footshock (chronic footshock, CFS), six accommodation sessions followed by one exposure to footshock (acute footshock, AFS) or handled similarly without receiving any footshock (no footshock, NFS). After the final footshock or NFS session, rats were anesthetized, a laminectomy performed and extracellular single-unit recordings of L6–S1 DHNs obtained in intact or spinalized preparations. Neurons were classified as Type I—inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II—not inhibited by HNCS—and characterized for spontaneous activity and for neuronal discharges evoked by graded UBD. A differential effect of footshock-induced stress was noted on neuronal subgroups. In intact preparations, Type I neurons were less responsive to UBD after either chronic or acute stress, while Type II neurons demonstrated significantly augmented responses to UBD. This enhanced neuronal responsiveness to UBD was present in spinalized preparations following exposure to CFS but not AFS. Type I neurons were still less responsive to stress in spinalized preparations following CFS and AFS. This study provides further evidence that (1) at least two populations of spinal neurons exist which encode for visceral stimuli and are likely to have distinct roles in visceral nociception, and that (2) the chronic stress-induced enhancement of DHN responses to UBD involves changes at the spinal level while the acute stress effects are dependent on a supraspinal substrate.
Neonatal bladder inflammation alters activity of adult rat spinal visceral nociceptive neurons
2010, Neuroscience Letters
Purpose: This investigation examined the effect of inflammation produced by intravesical zymosan during the neonatal period on spinal dorsal horn neuronal responses to urinary bladder distension (UBD) as adults. Methods: Female rat pups (P14–P16) were treated with intravesical zymosan or with anesthesia-only. These groups of rats were subdivided forming four groups: half received intravesical zymosan as adults and half received anesthesia-only. One day later, rats were anesthetized, the spinal cord was transected at a cervical level and extracellular single-unit recordings of L6-S1 dorsal horn neurons were obtained. Neurons were classified as Type I—inhibited by heterotopic noxious conditioning stimuli (HNCS) or as Type II – not inhibited by HNCS – and were characterized for Spontaneous Activity and responses to graded UBD (20–60 mm Hg). Results: 227 spinal dorsal horn neurons excited by UBD were characterized. In rats treated as neonates with anesthesia-only, Type II neurons demonstrated increased spontaneous and UBD-evoked activity following adult intravesical zymosan treatment whereas Type I neurons demonstrated decreased spontaneous and UBD-evoked activity relative to controls. In rats treated as neonates with intravesical zymosan, the spontaneous and UBD-evoked activity of both Type I and Type II neurons increased following adult intravesical zymosan treatment relative to controls. Conclusions: Neonatal bladder inflammation alters subsequent effects of acute bladder inflammation on spinal dorsal horn neurons excited by UBD such that overall there is greater sensory neuron activation. This may explain the visceral hypersensitivity noted in this model system and suggest that impaired inhibitory systems may be responsible.
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2015, BMC Urology
Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: Pathophysiology, translational relevance, and challenges
2015, American Journal of Physiology - Gastrointestinal and Liver Physiology

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Acute bladder inflammation differentially affects rat spinal visceral nociceptive neurons

Abstract

Section snippets

Acknowledgements

Pain

Pain

Br. J. Anaesth.

Pain

Brain Res.

Gastroenterology

J. Urol.

Reg. Anesth. Pain Med.

Neuroscience

Gastroenterology

J. Chem. Neuroanat.