Running Exercise Alleviates Pain and Promotes Cell Proliferation in a Rat Model of Intervertebral Disc Degeneration

Abstract

Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder. Physical exercise, which is clinically recommended by international guidelines, has proven to be effective for degenerative disc disease (DDD) patients. However, the mechanism underlying the analgesic effects of physical exercise on DDD remains largely unclear. The results of the present study showed that mechanical withdrawal thresholds of bilateral hindpaw were significantly decreased beginning on day three after intradiscal complete Freund’s adjuvant (CFA) injection and daily running exercise remarkably reduced allodynia in the CFA exercise group beginning at day 28 compared to the spontaneous recovery group (controls). The hindpaw withdrawal thresholds of the exercise group returned nearly to baseline at the end of experiment, but severe pain persisted in the control group. Histological examinations performed on day 70 revealed that running exercise restored the degenerative discs and increased the cell densities of the annulus fibrosus (AF) and nucleus pulposus (NP). Furthermore, immunofluorescence labeling revealed significantly higher numbers of 5-bromo-2-deoxyuridine (BrdU)-positive cells in the exercise group on days 28, 42, 56 and 70, which indicated more rapid proliferation compared to the control at the corresponding time points. Taken together, these results suggest that running exercise might alleviate the mechanical allodynia induced by intradiscal CFA injection via disc repair and cell proliferation, which provides new evidence for future clinical use.

Modest Amounts of Voluntary Exercise Reduce Pain- and Stress-Related Outcomes in a Rat Model of Persistent Hind Limb Inflammation

“…While sedentary inflamed rats experienced ongoing deficits in weight bearing over the three-week period, inflamed rats engaging in voluntary running exhibited a steady improvement in weight bearing capacity of the ipsilateral paw, achieving basal levels by three weeks post-CFA. In studies using forced exercise paradigms, while not all groups describe complete exercise-induced reversal of hypersensitivity to von Frey stimulation, most produce progressive improvements over spans of a few days to more than five weeks [9; 11; 18–24; 35; 54; 63; 69; 82; 93; 102; 103; 112; 132]. Strikingly, development of the CFA-induced thermal hypersensitivity observed in the sedentary inflamed group was prevented by only one week of voluntary running.…”

“…exercise initiated after injury) in human chronic pain populations are mixed, mainly due to differences in type of pain, type of exercise and exercise intensity [40; 55; 67; 72; 95]. In contrast, rodent studies employing therapeutic exercise uniformly show robust analgesic effects in a variety of persistent pain models and using a variety of exercise intensities [4; 9; 11; 18–24; 34; 35; 41; 54; 63; 69; 81; 82; 93; 102; 103; 112; 132]. Importantly, none of these studies assessed stress-related outcomes such as plasma corticosterone despite employing forced running paradigms that can be highly stressful [28; 36; 48; 62; 74; 80; 88; 89; 92].…”

The Impact of Exercise in Rodent Models of Chronic Pain

“…Under these conditions, the vast majority of studies (36 or 90%) reported that at least some form of therapeutic exercise was effective in reducing or reversing mechanical hypersensitivity. While three of the four studies showing no beneficial effect of therapeutic exercise on mechanical hypersensitivity initiated exercise 8 or more days after injury [ 92 , 98 , 118 ], other studies using similar delays in initiation of exercise were effective [ 87 , 91 •, 114 ••, 116 , 119 , 120 ]. Similarly, while two of the four studies showing no beneficial effect of therapeutic exercise on mechanical hypersensitivity used voluntary exercise paradigms [ 98 , 101 ], other studies using voluntary exercise were effective [ 87 , 97 , 99 ••, 100 ••].…”

Lumbar Degenerative Disease Part 1: Anatomy and Pathophysiology of Intervertebral Discogenic Pain and Radiofrequency Ablation of Basivertebral and Sinuvertebral Nerve Treatment for Chronic Discogenic Back Pain: A Prospective Case Series and Review of Literature

“…Physical exercise is clinically recommended in several guidelines to help in alleviating pain [67] Physical exercise helps in IVD cell proliferation in animal model studies, particularly in moderate to high volume low repetition and frequency exercises [68,69]. It has effect on paraspinal muscle strength and aids in reducing pain and disability [70].…”