Study of the role of the amygdala in the effects of stress on sensory processing of the urinary bladder.

摘要

Interstitial cystitis (IC) is a chronic visceral condition of the urinary bladder characterized by pelvic/suprapubic pain, and urinary frequency and urgency. There is no documented cause for IC, but a prominent role for stress in its pathophysiology and presentation are well-documented. In the clinical setting, IC pain-related symptomatology is exacerbated during periods of stress. Numerous laboratory studies of humans and animals have similarly demonstrated stress-induced visceral hypersensitivity. The amygdala is highly connected with physiological stress response systems and pain modulatory pathways, and its connectivity with these systems places it in a unique anatomical position for mediating the reciprocal relationship between pain and affective processes. This set of studies examined the role of the amygdala central nucleus (CeA) in modulation of urinary bladder nociceptive responses and physiological/behavioral indices of stress. Urinary bladder distension (UBD)-evoked visceromotor responses (VMRs), plasma corticosterone concentration, and spatiotemporal (% open arm time) and ethological behaviors (stretch-attend postures [SAPs], freezing, rearing) on the elevated plus maze (EPM) were measured in rats with CeA lesions following acute exposure to a footshock stressor and following acute chemical stimulation of the CeA with corticosterone. CeA lesions abolished acute footshock-induced bladder hyperalgesia and significantly decreased footshock-induced corticosterone release. Lesions significantly increased and decreased the frequency of SAPs and freezing, respectively. Acute corticosterone stimulation of the CeA significantly facilitated VMRs in a fashion similar to acute footshock exposure, but did not significantly affect corticosterone release before or after EPM testing. CeA stimulation with corticosterone significantly increased freezing behavior on the EPM, but did not significantly affect any other anxiety-like behaviors. Spinal c-Fos expression in response to UBD following corticosterone stimulation of the CeA was quantified. UBD significantly increased spinal c-Fos, and corticosterone stimulation of the CeA significantly reduced it. These findings indicate that the CeA plays a significant role in modulation of visceral nociceptive responses (via an as-of-yet undefined spinal mechanism) and HPA axis activity in response to acute experimental manipulations.