Neurobiological Changes in Rat Dorsal Root Ganglia due to Osteoarthritis and Exercise Treatment Open Access

Pucha, Krishnachaithanya (Spring 2021)

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Background: Osteoarthritis (OA) is the most common chronic degenerative disease of the joints characterized by the degradation of articular cartilage, subchondral bone sclerosis, synovial inflammation, and the growth of marginal bone spurs. OA often leads to reduced activity and further loss of function in the affected joint. Despite the socioeconomic costs of OA and its associated chronic pain, there are no FDA-approve disease modifying drugs available in the clinic. Exercise is the only disease modifying treatment that has shown evidence to reduce pain in certain patient populations. The objective of this study is to further elucidate the impact of exercise on OA pain progression, specifically in the context of neurobiological changes that occur in the dorsal root ganglia (DRG).

Methods: OA was induced in Lewis Rats  in the left knee via a medial meniscal transection (MMT) procedure. Three weeks post-OA induction, sham and MMT animals began a daily exercise regimen for three weeks. Through this six week period, Von Frey measurements were taken at baseline, 2-, 4- and 5-weeks post-surgery to measure pain sensitivity. Six weeks post-surgery, animals were euthanized and DRGs were collected from the thoracic (T9-T12) and lumbar (L1-L4) regions of the spinal column. These tissues were then cryosectioned and stained for the expression of CGRP and TRPV1.

Results: Representative images demonstrated successful isolation and staining of the DRG. No significant differences in the DRGs from the lumbar region were observed between groups, MMT animals demonstrated increased expression of CGRP in DRGs from the thoracic region compared to animals in the MMT with exercise group (MMT Ex). MMT and MMT Ex animals also demonstrated a decreased expression in TRPV1 expression in DRGs from the thoracic region compared to sham animals. In measures of pain sensitivity, by week 5, MMT Ex animals had higher pain sensitivity compared to non-exercised groups.

Conclusion: Though no changes were detected in DRGs that directly innervate the left knee (lumbar), changes in other regions of the body (thoracic) were observed due to OA induction. Additionally, administering an exercise therapy reversed these changes in MMT animals. These findings show potential evidence of exercise’s ability to mitigate neurobiological changes induces by OA and potentially help alleviate the pain associated with the disease. 

Table of Contents

Introduction. 1

Methods and Materials. 6

Animal Training. 6

Surgical Methods. 7

Von Frey Measurements. 7

Exercise Regimen. 8

Sample Preparation and Data Collection. 8

Immunological Staining of DRG.. 9

Image Analysis. 9

Statistical Analysis. 10

Results. 10

Exercise Compliance. 10

Representative Images of DRG IHC.. 10

Quantification of DRG IHC.. 11

Von Frey Measurements of Pain Sensitivity. 11

Discussion. 12

Figures. 18

Figure 1: Image processing. 18

Figure 2: Representative images of TRPV1 expression in DRGs. 19

Figure 3: Representative images of CGRP expression with DAPI in DRGs. 21

Figure 4: Quantitative analysis of TRPV1 and CGRP expression. 22

Figure 5: Von Frey measurements of Secondary Allodynia. 23

Bibliography 26

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