Impact of physical activity on pain perception in an animal model of endometriosis

Abstract

Background: Symptoms of endometriosis, such as pain and infertility, are considered significant sources of stress. In many chronic conditions, exercise can act as a stress buffer and influence pain perception. We tested the impact of swimming exercise on pain perception and pain receptors in an animal model of endometriosis.

Methods: Endometriosis (Endo) was induced in female rats by suturing uterine horn tissue next to the intestinal mesentery. Sham rats received sutures only. Rats were exposed to swimming exercise for 7 consecutive days, while no-exercise rats were left in the home cage. Fecal pellets were counted after swimming as an index of anxiety, and serum corticosterone levels measured. Pain perception was assessed using the hot plate test for hyperalgesia and Von Frey test for allodynia. Mu-opioid receptor (MOR) and neurokinin-1 receptor expression in the spinal cord was measured by immunofluorescence.

Results: Fecal pellet counts were higher in those animals that swam (p<0.05), but no significant difference in corticosterone was found. Although Endo-exercise rats had higher colonic damage (p<0.05) with more cellular infiltration, the lesions were smaller than in Endo-no exercise rats (p<0.05). Exercise did not ameliorate the hyperalgesia, whereas it improved allodynia in both groups. MOR expression was significantly higher in Endo-exercise vs. Endo-no exercise rats (p<0.01), similar to Sham-no exercise levels.

Conclusions: Our results point toward beneficial effects of swimming exercise during endometriosis progression. Physical interventions might be investigated further for their ability to reduce perceived stress and improve outcomes in endometriosis.

Keywords: Anxiety; Endometriosis; Exercise; Hyperalgesia; Opioid; Pain.

Fig. 1

Stress and anxiety levels. (A) Animals were subjected to a swimming exercise protocol for 7 consecutive days after surgical induction of endometriosis; HPT = Hot plate test; VFT = Von Frey filaments test. (B) Endo- and Sham-exercise rats had increased fecal pellet counts (*p<0.05, **p<0.01, vs. Endo–no exercise; ^#p<0.05, ^##p<0.01, vs. Sham–no exercise); (C) There was no difference in corticosterone levels between groups (n = 5–6, ± SEM).

Fig. 2

Effect of exercise on nociception. (A) Both endo groups reacted significantly faster to the hot plate as indicated by a decrease in latency after surgery and swim (^%p<0.05, ^%%p<0.01, vs. before surgery); (B) In the paw, Sham– and Endo–no exercise tolerated less force after surgery (^%p<0.05, vs. before surgery); (C) In the abdomen, there was no difference over time between groups, although the Endo-exercise group showed a trend toward increased tolerance. (n = 5–6, ± SEM).

Fig. 3

Effect of exercise on implant size. None of the Sham group developed lesions. (A) Exposure to exercise decreased the number of lesions developed (*p<0.05); (B) Representative photograph of lesions collected (both grade 5); (C) The Endo–no exercise animals developed a lesion in 100% of their sutures; (D) Endo-exercise animals developed lesions of a smaller size than those found in the Endo–no exercise rats (*p<0.05; n = 5–6, ± SEM).

Fig. 4

Effect of swimming on colonic damage and neutrophil infiltration in colon and uterus. (A) Endo-exercise had more colonic damage compared to Sham-exercise; (B) there was no difference between groups at a microscopic level; (C) Endo-exercise had higher myeloperoxidase levels in the colon compared with Sham–no exercise; (D) there was no difference in myeloperoxidase levels between groups in the uterine tissue (^$p<0.05, vs. Sham-exercise; ^#p<0.05, vs. Sham–no exercise; n = 4–6, ± SEM).

Fig. 5

Spinal cord mu-opioid receptor (MOR) expression in rats exposed to forced swimming exercise. (A) Endo-exercise animals had increased expression of MOR in the thoracic spinal cord compared with Endo–no exercise rats (**p<0.01) or Sham-exercise (^$p<0.05). Sham–no exercise had higher expression of MOR in the thoracic (*p<0.05) (A) and lumbar (*p<0.05) (B) spinal cord when compared with Endo–no exercise rats. Representative MOR immunofluorescent staining of thoracic sections from Endo–no exercise rats (C) and Endo-exercise animals (D) (1:100 at ×40; n = 5–6, ± SEM).

Fig. 6

Spinal cord substance P (Sub P) expression in rats exposed to forced swimming exercise. (A) Endo-exercise animals had decreased expression of Sub P in the lumbar spinal cord compared with Sham–no exercise (right side; *p<0.05); Representative Sub P immunohistochemistry staining of lumbar sections from Sham–no exercise (B), and Endo-exercise animals (C) (1:200 at ×10; n = 5–6, ± SEM).