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Running exercise alleviates pain and promotes cell proliferation in a rat model of intervertebral disc degeneration.

Luan S, Wan Q, Luo H, Li X, Ke S, Lin C, Wu Y, Wu S, Ma C - Int J Mol Sci (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. luanshuo126@163.com.

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.

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Related in: MedlinePlus

Photomicrographs of midsagittal sections of complete Freund’s adjuvant (CFA)-injected and sham-operation discs. (A,B) The discs of the CFA model rats exhibited dehydrated nucleus pulposus and blurred boundaries between the nucleus pulposus (NP) and anulus fibrosus (AF) areas at day 14 after CFA injection; (C,D) Intact NP and the clear distinction between NP and AF in discs of sham exercise groups at day 14 and day 70; (E,F) The gradual recovery processes were observed at day 42 and day 56 in the CFA exercise group; (G) Restored disc structures in the exercise group at day 70 after CFA injection; (H) Remarkable degenerative changes in the spontaneous recovery group at day 70 after CFA injection; (I,J) Quantitative results of NP and AF cell numbers in the CFA groups and sham-operation groups. The CFA exercise group revealed significant increases in both the NP (0.5-fold, p ˂ 0.05) and AF (1.4-fold, p ˂ 0.01) areas compared to the CFA spontaneous recovery group at day 70. The sham exercise group also showed significant increases of NP and AF compared to the baseline from day 42 (p ˂ 0.05) and maintained till the day 70. The sham spontaneous recovery group did not show obvious changes in NP or AF cell numbers throughout the experiment. The data are expressed as the means ± SDs, n = 8 in each CFA groups, n = 5 in each sham-operation groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA spontaneous recovery subgroups, and the sham exercise subgroups vs. the sham spontaneous recovery subgroups at the specific time points. One-way analysis of variance (ANOVA) was used to analyze the within-group differences, and subsequent post-hoc tests were used to evaluate the differences between the specific time points and the baseline level in each group. *p ˂ 0.05, **p ˂ 0.01 compared to baseline; #p ˂ 0.05, ##p ˂ 0.01 CFA exercise group compared to the CFA spontaneous recovery group at the corresponding time points. ※p ˂ 0.05 sham exercise group compared to the sham spontaneous recovery group at the corresponding time points.
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ijms-16-02130-f002: Photomicrographs of midsagittal sections of complete Freund’s adjuvant (CFA)-injected and sham-operation discs. (A,B) The discs of the CFA model rats exhibited dehydrated nucleus pulposus and blurred boundaries between the nucleus pulposus (NP) and anulus fibrosus (AF) areas at day 14 after CFA injection; (C,D) Intact NP and the clear distinction between NP and AF in discs of sham exercise groups at day 14 and day 70; (E,F) The gradual recovery processes were observed at day 42 and day 56 in the CFA exercise group; (G) Restored disc structures in the exercise group at day 70 after CFA injection; (H) Remarkable degenerative changes in the spontaneous recovery group at day 70 after CFA injection; (I,J) Quantitative results of NP and AF cell numbers in the CFA groups and sham-operation groups. The CFA exercise group revealed significant increases in both the NP (0.5-fold, p ˂ 0.05) and AF (1.4-fold, p ˂ 0.01) areas compared to the CFA spontaneous recovery group at day 70. The sham exercise group also showed significant increases of NP and AF compared to the baseline from day 42 (p ˂ 0.05) and maintained till the day 70. The sham spontaneous recovery group did not show obvious changes in NP or AF cell numbers throughout the experiment. The data are expressed as the means ± SDs, n = 8 in each CFA groups, n = 5 in each sham-operation groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA spontaneous recovery subgroups, and the sham exercise subgroups vs. the sham spontaneous recovery subgroups at the specific time points. One-way analysis of variance (ANOVA) was used to analyze the within-group differences, and subsequent post-hoc tests were used to evaluate the differences between the specific time points and the baseline level in each group. *p ˂ 0.05, **p ˂ 0.01 compared to baseline; #p ˂ 0.05, ##p ˂ 0.01 CFA exercise group compared to the CFA spontaneous recovery group at the corresponding time points. ※p ˂ 0.05 sham exercise group compared to the sham spontaneous recovery group at the corresponding time points.

Mentions: Sections stained with hematoxylin and eosin (HE) were used to evaluate the morphological changes. Sections from rats killed at day 14 after CFA injection exhibited obvious dehydrated nucleus pulposus (NP) and blurred boundaries between NP and anulus fibrosus (AF), which indicated that significant degenerative changes had occurred in CFA groups (Figure 2A,B). The histological examinations of sham exercise groups showed nearly intact structures at day 14 and day 70 (Figure 2C,D). Furthermore, the gradual recovery could be observed in the CFA exercise group as time went by (Figure 2E,F). After running for 8 weeks (day 70), the disc of CFA exercise group revealed a relative normal NP and a distinct boundary between the NP and AF (Figure 2G), while progressions of the decrease in the NP and disorganized lamellae were observed in the CFA spontaneous recovery group at the same time point (Figure 2H). The quantification of the disc cells in the CFA groups revealed a significant decrease in both NP and AF compared to the baseline at day 14 (p ˂ 0.01), however, no significant changes were detected in the sham-operation groups at the same time point. Furthermore, the cell counts of the CFA exercise group increased constantly, which showed a 0.5-fold increase of the NP (p ˂ 0.05) and a 1.4-fold increase of the AF (p ˂ 0.01) compared to the CFA spontaneous recovery group at day 70. In the sham exercise group, the significant increases of NP and AF cells were observed at day 42 (p ˂ 0.05) and maintained till the end of experiment, while the numbers of both NP and AF cells remained unchanged in the sham spontaneous recovery group till day 70. (Figure 2I,J).


Running exercise alleviates pain and promotes cell proliferation in a rat model of intervertebral disc degeneration.

Luan S, Wan Q, Luo H, Li X, Ke S, Lin C, Wu Y, Wu S, Ma C - Int J Mol Sci (2015)

Photomicrographs of midsagittal sections of complete Freund’s adjuvant (CFA)-injected and sham-operation discs. (A,B) The discs of the CFA model rats exhibited dehydrated nucleus pulposus and blurred boundaries between the nucleus pulposus (NP) and anulus fibrosus (AF) areas at day 14 after CFA injection; (C,D) Intact NP and the clear distinction between NP and AF in discs of sham exercise groups at day 14 and day 70; (E,F) The gradual recovery processes were observed at day 42 and day 56 in the CFA exercise group; (G) Restored disc structures in the exercise group at day 70 after CFA injection; (H) Remarkable degenerative changes in the spontaneous recovery group at day 70 after CFA injection; (I,J) Quantitative results of NP and AF cell numbers in the CFA groups and sham-operation groups. The CFA exercise group revealed significant increases in both the NP (0.5-fold, p ˂ 0.05) and AF (1.4-fold, p ˂ 0.01) areas compared to the CFA spontaneous recovery group at day 70. The sham exercise group also showed significant increases of NP and AF compared to the baseline from day 42 (p ˂ 0.05) and maintained till the day 70. The sham spontaneous recovery group did not show obvious changes in NP or AF cell numbers throughout the experiment. The data are expressed as the means ± SDs, n = 8 in each CFA groups, n = 5 in each sham-operation groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA spontaneous recovery subgroups, and the sham exercise subgroups vs. the sham spontaneous recovery subgroups at the specific time points. One-way analysis of variance (ANOVA) was used to analyze the within-group differences, and subsequent post-hoc tests were used to evaluate the differences between the specific time points and the baseline level in each group. *p ˂ 0.05, **p ˂ 0.01 compared to baseline; #p ˂ 0.05, ##p ˂ 0.01 CFA exercise group compared to the CFA spontaneous recovery group at the corresponding time points. ※p ˂ 0.05 sham exercise group compared to the sham spontaneous recovery group at the corresponding time points.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4307353&req=5

ijms-16-02130-f002: Photomicrographs of midsagittal sections of complete Freund’s adjuvant (CFA)-injected and sham-operation discs. (A,B) The discs of the CFA model rats exhibited dehydrated nucleus pulposus and blurred boundaries between the nucleus pulposus (NP) and anulus fibrosus (AF) areas at day 14 after CFA injection; (C,D) Intact NP and the clear distinction between NP and AF in discs of sham exercise groups at day 14 and day 70; (E,F) The gradual recovery processes were observed at day 42 and day 56 in the CFA exercise group; (G) Restored disc structures in the exercise group at day 70 after CFA injection; (H) Remarkable degenerative changes in the spontaneous recovery group at day 70 after CFA injection; (I,J) Quantitative results of NP and AF cell numbers in the CFA groups and sham-operation groups. The CFA exercise group revealed significant increases in both the NP (0.5-fold, p ˂ 0.05) and AF (1.4-fold, p ˂ 0.01) areas compared to the CFA spontaneous recovery group at day 70. The sham exercise group also showed significant increases of NP and AF compared to the baseline from day 42 (p ˂ 0.05) and maintained till the day 70. The sham spontaneous recovery group did not show obvious changes in NP or AF cell numbers throughout the experiment. The data are expressed as the means ± SDs, n = 8 in each CFA groups, n = 5 in each sham-operation groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA spontaneous recovery subgroups, and the sham exercise subgroups vs. the sham spontaneous recovery subgroups at the specific time points. One-way analysis of variance (ANOVA) was used to analyze the within-group differences, and subsequent post-hoc tests were used to evaluate the differences between the specific time points and the baseline level in each group. *p ˂ 0.05, **p ˂ 0.01 compared to baseline; #p ˂ 0.05, ##p ˂ 0.01 CFA exercise group compared to the CFA spontaneous recovery group at the corresponding time points. ※p ˂ 0.05 sham exercise group compared to the sham spontaneous recovery group at the corresponding time points.
Mentions: Sections stained with hematoxylin and eosin (HE) were used to evaluate the morphological changes. Sections from rats killed at day 14 after CFA injection exhibited obvious dehydrated nucleus pulposus (NP) and blurred boundaries between NP and anulus fibrosus (AF), which indicated that significant degenerative changes had occurred in CFA groups (Figure 2A,B). The histological examinations of sham exercise groups showed nearly intact structures at day 14 and day 70 (Figure 2C,D). Furthermore, the gradual recovery could be observed in the CFA exercise group as time went by (Figure 2E,F). After running for 8 weeks (day 70), the disc of CFA exercise group revealed a relative normal NP and a distinct boundary between the NP and AF (Figure 2G), while progressions of the decrease in the NP and disorganized lamellae were observed in the CFA spontaneous recovery group at the same time point (Figure 2H). The quantification of the disc cells in the CFA groups revealed a significant decrease in both NP and AF compared to the baseline at day 14 (p ˂ 0.01), however, no significant changes were detected in the sham-operation groups at the same time point. Furthermore, the cell counts of the CFA exercise group increased constantly, which showed a 0.5-fold increase of the NP (p ˂ 0.05) and a 1.4-fold increase of the AF (p ˂ 0.01) compared to the CFA spontaneous recovery group at day 70. In the sham exercise group, the significant increases of NP and AF cells were observed at day 42 (p ˂ 0.05) and maintained till the end of experiment, while the numbers of both NP and AF cells remained unchanged in the sham spontaneous recovery group till day 70. (Figure 2I,J).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Rehabilitation Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. luanshuo126@163.com.

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.

Show MeSH
Related in: MedlinePlus