Chronic psychological stress enhances nociceptive processing in the urinary bladder in high-anxiety rats

Abstract

This study sought to determine whether acute and/or chronic psychological stress produce changes in urinary bladder nociception. Female Sprague-Dawley (SD; low/moderate anxiety) or Wistar-Kyoto (WK; high-anxiety) rats were exposed to either an acute (1 day) or a chronic (10 days) water avoidance stress paradigm or a sham stress paradigm. Paw withdrawal thresholds to mechanical and thermal stimuli and fecal pellet output, were quantified at baseline and after the final stress or sham stress exposure. Rats were then sedated, and visceromotor responses (VMRs) to urinary bladder distension (UBD) were recorded. While acute stress exposure did not significantly alter bladder nociceptive responses in either strain of rats, WK rats exposed to a chronic stress paradigm exhibited enhanced responses to UBD. These high-anxiety rats also exhibited somatic analgesia following acute, but not chronic, stress. Furthermore, WK rats had greater fecal pellet output than SD rats when stressed. Significant stress-induced changes in nociceptive responses to mechanical stimuli were observed in SD rats. That chronic psychological stress significantly enhanced bladder nociceptive responses only in high-anxiety rats provides further support for a critical role of genetics, stress and anxiety as exacerbating factors in painful urogenital disorders such as interstitial cystitis (IC).

Figure 1

Chronic WA stress (○; N=8) induced bladder hyperalgesia in high-anxiety WK rats (A), manifested as significantly enhanced VMRs compared to those evoked by UBD after chronic WA sham exposure (●; N=10). Nociceptive responses were the same in SD rats, whether they were exposed to the chronic WA stress (○; N=5) or the chronic WA sham (●; N=6) condition (B). Acute WA stress did not significantly alter bladder nociceptive responses in either WK (C) or SD (D) rats. Rats exposed to the WA stress (○; N=11 for WK; N=14 for SD) or WA sham (●; N=9 for WK; N=13 for SD) conditions demonstrated similar responses as naïve animals (▲; N=10 for WK; N=13 for SD). * indicates significantly different from WA sham condition (p<0.05).

Figure 2

Immediately following 1 hour of WA stress, mechanical (A) and thermal (B) nociceptive responses were significantly attenuated in WK rats. Acute WA stress induced mechanical (C), but not thermal (D) analgesia in SD rats. N=9-14/group. * and ** indicate p<0.05 and p<0.01, respectively.

Figure 3

Neither mechanical (A) nor thermal (B) nociceptive responses were significantly altered following 10 days of WA stress. N=5-12/group.

Figure 4

On day 1 of the chronic stress paradigm, fecal pellet output of both strains of WA stress rats was significantly enhanced relative to their WA sham counterparts (WK: Mann-Whitney U=62.50, p=0.021, SD: Mann-Whitney U=27.00, p=0.006). Furthermore, sham WK rats had significantly greater fecal pellet output than sham SD rats on day 1 (Mann-Whitney U=48.00, p=.0125), but there were no significant differences between groups in the stress condition (Mann-Whitney U=30.50, p=0.06). However, by day 10, WK rats in the stress condition had significantly greater fecal pellet output than did SD rats in the same condition (Mann-Whitney U=30.00, p=.037), but there were no differences in the sham groups (Mann-Whitney U=33.00, p=0.218). N=5-12/group. ** indicates significantly different from WA sham stress at p<0.05. # indicates significantly different from corresponding SD group.