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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: Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder.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).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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Comparisons of the 5-bromo-2-deoxyuridine (BrdU)-positive cells in four different areas between the CFA exercise group and CFA spontaneous recovery group. (A) The peripheral epiphyseal cartilage (pEC) area of the exercise group at day 42; (B) The pEC area of the spontaneous recovery group at day 42; (C) the outer rings of the AF (AFo) area of the exercise group at day 42; (D) the AFo area of the spontaneous recovery group at day 42; and (E) Comparisons of the BrdU-positive cells between the CFA exercise group and the spontaneous recovery group. The BrdU-positive cells in the stem cell niche (SN) and pEC of the exercise group were significantly increased from the early time point of day 21 (p ˂ 0.05), peaked at day 28 (p ˂ 0.01) and were maintained at high levels until the end of the experiment compared to the spontaneous recovery group (p ˂ 0.05). The cell numbers in the AFo and the inner rings of the AF (AFi) areas of the exercise group were higher on days 28, 42, 56 and 70 (p ˂ 0.05) and peaked at the relatively later time point of day 42 (p ˂ 0.01). The data are expressed as the means ± SDs, n = 8 in each CFA groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA 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 the CFA spontaneous recovery group at the corresponding time points.
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ijms-16-02130-f003: Comparisons of the 5-bromo-2-deoxyuridine (BrdU)-positive cells in four different areas between the CFA exercise group and CFA spontaneous recovery group. (A) The peripheral epiphyseal cartilage (pEC) area of the exercise group at day 42; (B) The pEC area of the spontaneous recovery group at day 42; (C) the outer rings of the AF (AFo) area of the exercise group at day 42; (D) the AFo area of the spontaneous recovery group at day 42; and (E) Comparisons of the BrdU-positive cells between the CFA exercise group and the spontaneous recovery group. The BrdU-positive cells in the stem cell niche (SN) and pEC of the exercise group were significantly increased from the early time point of day 21 (p ˂ 0.05), peaked at day 28 (p ˂ 0.01) and were maintained at high levels until the end of the experiment compared to the spontaneous recovery group (p ˂ 0.05). The cell numbers in the AFo and the inner rings of the AF (AFi) areas of the exercise group were higher on days 28, 42, 56 and 70 (p ˂ 0.05) and peaked at the relatively later time point of day 42 (p ˂ 0.01). The data are expressed as the means ± SDs, n = 8 in each CFA groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA 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 the CFA spontaneous recovery group at the corresponding time points.

Mentions: Proliferating cells with BrdU labeling were detected in four different areas of CFA groups within the IVDs that included the stem cell niche (SN), peripheral epiphyseal cartilage (pEC), outer rings of the AF (AFo) and inner rings of the AF (AFi). The results revealed that the BrdU-positive cells in the pEC area were primarily round in shape and that the proliferation rate was significantly promoted by running exercise. The remarkable increase in the BrdU-positive cells began at day 21 (p ˂ 0.05), peaked at day 28 (p ˂ 0.01) and was maintained until the end of experiment (p ˂ 0.05) compared to the spontaneous recovery group at the corresponding time points (Figure 3A,B,E). Along with the increase in the BrdU-positive cells with elongated or elliptical shapes, we also observed that daily running exercise significantly promoted cell proliferation within the SN, AFo (Figure 3C–E) and AFi areas in similar manners (Figure 3).


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)

Comparisons of the 5-bromo-2-deoxyuridine (BrdU)-positive cells in four different areas between the CFA exercise group and CFA spontaneous recovery group. (A) The peripheral epiphyseal cartilage (pEC) area of the exercise group at day 42; (B) The pEC area of the spontaneous recovery group at day 42; (C) the outer rings of the AF (AFo) area of the exercise group at day 42; (D) the AFo area of the spontaneous recovery group at day 42; and (E) Comparisons of the BrdU-positive cells between the CFA exercise group and the spontaneous recovery group. The BrdU-positive cells in the stem cell niche (SN) and pEC of the exercise group were significantly increased from the early time point of day 21 (p ˂ 0.05), peaked at day 28 (p ˂ 0.01) and were maintained at high levels until the end of the experiment compared to the spontaneous recovery group (p ˂ 0.05). The cell numbers in the AFo and the inner rings of the AF (AFi) areas of the exercise group were higher on days 28, 42, 56 and 70 (p ˂ 0.05) and peaked at the relatively later time point of day 42 (p ˂ 0.01). The data are expressed as the means ± SDs, n = 8 in each CFA groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA 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 the CFA spontaneous recovery group at the corresponding time points.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4307353&req=5

ijms-16-02130-f003: Comparisons of the 5-bromo-2-deoxyuridine (BrdU)-positive cells in four different areas between the CFA exercise group and CFA spontaneous recovery group. (A) The peripheral epiphyseal cartilage (pEC) area of the exercise group at day 42; (B) The pEC area of the spontaneous recovery group at day 42; (C) the outer rings of the AF (AFo) area of the exercise group at day 42; (D) the AFo area of the spontaneous recovery group at day 42; and (E) Comparisons of the BrdU-positive cells between the CFA exercise group and the spontaneous recovery group. The BrdU-positive cells in the stem cell niche (SN) and pEC of the exercise group were significantly increased from the early time point of day 21 (p ˂ 0.05), peaked at day 28 (p ˂ 0.01) and were maintained at high levels until the end of the experiment compared to the spontaneous recovery group (p ˂ 0.05). The cell numbers in the AFo and the inner rings of the AF (AFi) areas of the exercise group were higher on days 28, 42, 56 and 70 (p ˂ 0.05) and peaked at the relatively later time point of day 42 (p ˂ 0.01). The data are expressed as the means ± SDs, n = 8 in each CFA groups. Independent-samples t tests were used to examine the differences between the CFA running exercise subgroups vs. the CFA 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 the CFA spontaneous recovery group at the corresponding time points.
Mentions: Proliferating cells with BrdU labeling were detected in four different areas of CFA groups within the IVDs that included the stem cell niche (SN), peripheral epiphyseal cartilage (pEC), outer rings of the AF (AFo) and inner rings of the AF (AFi). The results revealed that the BrdU-positive cells in the pEC area were primarily round in shape and that the proliferation rate was significantly promoted by running exercise. The remarkable increase in the BrdU-positive cells began at day 21 (p ˂ 0.05), peaked at day 28 (p ˂ 0.01) and was maintained until the end of experiment (p ˂ 0.05) compared to the spontaneous recovery group at the corresponding time points (Figure 3A,B,E). Along with the increase in the BrdU-positive cells with elongated or elliptical shapes, we also observed that daily running exercise significantly promoted cell proliferation within the SN, AFo (Figure 3C–E) and AFi areas in similar manners (Figure 3).

Bottom Line: Chronic low back pain accompanied by intervertebral disk degeneration is a common musculoskeletal disorder.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).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