Background & Aims

Early life stress exposure has been correlated with pain and cognitive symptom severity in patients with urologic chronic pelvic pain syndrome (UCPPS) (1-7). Neuroimaging studies revealed changes in gray matter volume, neurochemical concentration, and functional connectivity that correlate with patients’ pain symptomology (8). Our lab established a mouse model of early life stress using neonatal maternal separation (NMS) which recapitulates clinical hallmarks of UCPPS including urogenital hypersensitivity, decreased hippocampal volume, and reduced neuronal integrity (9-21). We have previously shown that exposure to water avoidance stress (WAS) exacerbates the NMS phenotype, while voluntary wheel running attenuates NMS-related outcomes. We hypothesize that NMS-induced changes in the hippocampus can be modified by increasing physical activity, thereby attenuating urogenital hypersensitivity, cognitive deficits, and hippocampal neurochemical disturbances following exposure to WAS.

Methods

NMS lasts from postnatal day 1-21 and consists of a daily 3-hr separation. Exercise (ex) was examined using voluntary wheel running in the home cage. WAS is a single, 1-hr exposure. Urogenital sensitivity was evaluated as perigenital mechanical withdrawal threshold in males and visceromotor response to urinary bladder distention in females. We examined cognition with repeated Y-maze and radial arm maze (RAM) performance at 6 and 12 months of age. Hippocampal integrity was evaluated by 9.4T 1H-magnetic resonance imaging and spectroscopy (MRI/MRS). Both male (m) and female (f) mice were used for these studies.

Results

Increased visceromotor response to urinary bladder distention was attenuated by exercise in NMS-f both at baseline and post-WAS. Exercise increased baseline prostate mechanical withdrawal threshold in NMS-m but did not prevent WAS-induced sensitivity. No significant cognitive deficits were observed. MRS revealed sex and hemisphere-dependent differences in hippocampal neurochemical concentrations post-WAS. In the left-f hippocampus, a WAS effect was observed on total creatine (tCr) and phosphocholine (pCho). An interaction of WAS-NMS-Ex was observed on glutamate (glu) and pCho. In the right-f, we observed a WAS effect on lactate and a WAS-NMS interaction on glutathione and aspartate. In the left-m hippocampus, a WAS effect was observed on lactate, n-acetylaspartate (NAA), glu, tCr, total choline (tCho), and taurine, as well as a WAS-NMS-Ex interaction on n-acetylaspartate. In the right-m, a main effect of WAS and a WAS-NMS interaction was observed for GABA, NAA, tCho, and glu.

Conclusions

These results suggest complex contributions of NMS, exercise, and stress to perceptions of pain, cognitive performance, and hippocampal integrity. At voluntary levels, exercise prevents WAS-induced hyperalgesia in females but does not prevent WAS-induced allodynia in males. The cognition data, although not significant, does indicate some interesting trends toward sex differences in NMS-induced cognitive dysfunction. MRS results confirm sex differences in acute stress response, as well as hemisphere-specific NMS-induced hippocampal dysfunction. Voluntary exercise may be beneficial for some, though not all, NMS-induced hippocampal neurochemical changes.

References

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Presenting Author

Tara McQuillan

Poster Authors

Tara McQuillan

BSc

University of Kansas Medical Center

Lead Author

E-mail

Rebecca M Foright

PhD

University of Kansas Medical Center

Lead Author

E-mail

Jenna M Frick

PhD

University of Kansas Medical Center

Lead Author

E-mail

Brittni M Levasseur

PhD

University of Kansas Medical Center

Lead Author

E-mail

In-Young Choi

PhD

University of Kansas Medical Center

Lead Author

E-mail

Phil Lee

PhD

University of Kansas Medical Center

Lead Author

E-mail

Munish Chauhan

PhD

University of Kansas Medical Center

Lead Author

E-mail

Carly Gagnon

University of Kansas Medical Center

Lead Author

E-mail

Julie Christianson

Univ Kansas Med Center

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Abdominal and Pelvic Pain