Bladder Distension Increases Blood Flow in Pain Related Brain Structures in Subjects with Interstitial Cystitis

Deutsch, G; Deshpande, Hrishikesh; Frölich, Michael A.; Lai, H. Henry; Ness, Timothy J.

doi:10.1016/j.juro.2016.03.135

Cited by 21 publications

(32 citation statements)

References 32 publications

(46 reference statements)

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“…33 Recent brain imaging studies in patients with chronic bladder pain have reported hemispheric asymmetries in amygdala structural integrity, anatomical connectivity, and functional activity. 1,3,16,27 These data are noteworthy because noxious bladder signals are presumed to equally engage both sides of the brain through bilateral peripheral and spinal afferents. 10,36 …”

Section: Introductionmentioning

confidence: 95%

Divergent functions of the left and right central amygdala in visceral nociception

Sadler

McQuaid²,

Cox³

et al. 2016

Pain

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The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2–mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase–activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2–mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain–like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

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Section: Introductionmentioning

confidence: 95%

Divergent functions of the left and right central amygdala in visceral nociception

Sadler

McQuaid²,

Cox³

et al. 2016

Pain

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“…83,84 Regions in this network frequently identified with both functional and structural abnormalities in patients with IC/BPS include sensorimotor regions, such as primary somatosensory cortex, supplementary motor cortex, and the thalamus, but also regions deeply engaged in the modulation of emotions, such as the cingulate, insula, and amygdala. [16][17][18][20][21][22][23][24]85,86 In our rodent model, WAS animals compared with SHAM demonstrated a decreased pressure threshold and VMR threshold triggering the voiding phase. Our prior study 29 demonstrated that WAS compared with SHAM animals demonstrated significant changes in cerebral activation during passive bladder distension.…”

Section: Discussionmentioning

confidence: 75%

“…This posterior midline cortical region contributes to pain and to micturition circuits, shows stress effects, and has been reported to demonstrated altered functionality in patients with IC/BPS. 19,85 Given the actions of CTX on the glutamate transporter, our results suggest the possibility of glutamatergic pharmacologic strategies in modulating stress-related bladder dysfunction.…”

Section: Discussionmentioning

confidence: 81%

“…Cerebral perfusion mapping revealed stress effects in brain regions previously noted by others to be responsive to passive bladder filling. 85,120,121 Administration of CTX during stress exposure diminished visceral hypersensitivity and attenuated many of the stress-related functional brain changes within the supraspinal micturition circuit and in overlapping nodes of the limbic and nociceptive systems, including the pCg/antRS, somatosensory cortex, and anterior thalamus. A significant differential effect of CTX on functional connectivity of the pCg/antRS cortex of stressed animals compared with controls was noted.…”

Section: Discussionmentioning

confidence: 99%

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Ceftriaxone inhibits stress‐induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study

Holschneider¹,

Wang²,

Chang

et al. 2020

Neurourology and Urodynamics

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Aims Emotional stress plays a role in the exacerbation and development of interstitial cystitis/bladder pain syndrome (IC/BPS). Given the significant overlap of brain circuits involved in stress, anxiety, and micturition, and the documented role of glutamate in their regulation, we examined the effects of an increase in glutamate transport on central amplification of stress‐induced bladder hyperalgesia, a core feature of IC/BPS. Methods Wistar‐Kyoto rats were exposed to water avoidance stress (WAS, 1 hour/day x 10 days) or sham stress, with subgroups receiving daily administration of ceftriaxone (CTX), an activator of glutamate transport. Thereafter, cystometrograms were obtained during bladder infusion with visceromotor responses (VMR) recorded simultaneously. Cerebral blood flow (CBF) mapping was performed by intravenous injection of [14C]‐iodoantipyrine during passive bladder distension. Regional CBF was quantified in autoradiographs of brain slices and analyzed in three dimensional reconstructed brains with statistical parametric mapping. Results WAS elicited visceral hypersensitivity during bladder filling as demonstrated by a decreased pressure threshold and VMR threshold triggering the voiding phase. Brain maps revealed stress effects in regions noted to be responsive to bladder filling. CTX diminished visceral hypersensitivity and attenuated many stress‐related cerebral activations within the supraspinal micturition circuit and in overlapping limbic and nociceptive regions, including the posterior midline cortex (posterior cingulate/anterior retrosplenium), somatosensory cortex, and anterior thalamus. Conclusions CTX diminished bladder hyspersensitivity and attenuated regions of the brain that contribute to nociceptive and micturition circuits, show stress effects, and have been reported to demonstrated altered functionality in patients with IC/BPS. Glutamatergic pharmacologic strategies modulating stress‐related bladder dysfunction may be a novel approach to the treatment of IC/BPS.

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“…Unlike PET scans that require the administration of radioactive intravenous contrast to measure cerebral perfusion, ASL uses inverted proton spins of magnetically labeled water in the blood as a tracer. Using continuous ASL, Deutsch et al reported quantitative increases in absolute rCBF in several regions of the brain involved in the pain matrix in women with interstitial cystitis [ 8 ]. However, cerebral perfusion changes associated with urinary urgency in women with OAB have not been quantified.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Changes in Cerebral Perfusion during Urinary Urgency in Women with Overactive Bladder

Arya

Weissbart

et al. 2017

BioMed Research International

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Purpose To quantitatively measure changes in cerebral perfusion in select regions of interest in the brain during urinary urgency in women with overactive bladder (OAB) using arterial spin labeling (ASL). Methods Twelve women with OAB and 10 controls underwent bladder filling and rated urinary urgency (scale 0–10). ASL fMRI scans were performed (1) in the low urgency state after voiding and (2) high urgency state after drinking oral fluids. Absolute regional cerebral blood flow (rCBF) in select regions of interest was compared between the low and high urgency states. Results There were no significant differences in rCBF between the low and high urgency states in the control group. In the OAB group, rCBF (mean ± SE, ml/100 g/min) increased by 10–14% from the low to the high urgency state in the right anterior cingulate cortex (ACC) (44.56 ± 0.59 versus 49.52 ± 1.49, p < 0.05), left ACC (49.29 ± 0.85 versus 54.02 ± 1.46, p < 0.05), and left insula (50.46 ± 1.72 versus 54.99 ± 1.09, p < 0.05). Whole-brain analysis identified additional areas of activation in the right insula, right dorsolateral prefrontal cortex, and pons/midbrain area. Conclusions Urinary urgency is associated with quantitative increase in cerebral perfusion in regions of the brain associated with processing emotional response to discomfort.

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Bladder Distension Increases Blood Flow in Pain Related Brain Structures in Subjects with Interstitial Cystitis

Cited by 21 publications

References 32 publications

Divergent functions of the left and right central amygdala in visceral nociception

Divergent functions of the left and right central amygdala in visceral nociception

Ceftriaxone inhibits stress‐induced bladder hyperalgesia and alters cerebral micturition and nociceptive circuits in the rat: A multidisciplinary approach to the study of urologic chronic pelvic pain syndrome research network study

Quantitative Changes in Cerebral Perfusion during Urinary Urgency in Women with Overactive Bladder

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