Characterizing Activity and Muscle Atrophy Changes in Rats With Neuropathic Pain

The study of neuropathic pain has focused on changes within the nervous system, but little research has described systemic changes that may accompany neuropathic pain. Objective: As part of a larger project characterizing the metabolic, activity, and musculoskeletal changes associated with neuropathic pain, the objective of the current study was to characterize changes in spontaneous activity and skeletal muscle mass using an established animal model of neuropathic pain, the chronic constriction injury (CCI) model. Method: Male Sprague-Dawley rats were used in this pre- and posttest quasi-experimental study. The experimental group ( n = 13) received CCI surgery, while age- and weight-matched rats received sham surgery (SHAM; n = 5). Thermal testing verified the presence of neuropathic pain. Spontaneous cage activity was measured gravimetrically prior to and following CCI ( n = 4). Animals were euthanized and skeletal muscle was dissected and weighed to determine muscle atrophy. Results: Shorter foot withdrawal latency of the ipsilateral hind limb confirmed the presence of thermal hyperalgesia in CCI rats, a sign of neuropathic pain. Weight increased in both CCI and SHAM rats. Spontaneous activity decreased following CCI ligation. Muscles of the ipsilateral hind limb weighed significantly less than contralateral hind limb muscles in CCI rats 2 and 6 weeks after surgery. In addition, CCI rats had smaller ipsilateral hind limb muscles than SHAM rats. Conclusion: Neuropathic pain contributes to skeletal muscle atrophy and decreases in activity in rats.

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Forkhead box O3 plays a role in skeletal muscle atrophy through expression of E3 ubiquitin ligases MuRF-1 and atrogin-1 in Cushing’s syndrome

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00389.2016 ◽

2017 ◽

Vol 312 (6) ◽

pp. E495-E507 ◽

Cited By ~ 15

Author(s):

Seol-Hee Kang ◽

Hae-Ahm Lee ◽

Mina Kim ◽

Eunjo Lee ◽

Uy Dong Sohn ◽

...

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Cushing’S Syndrome ◽

Ubiquitin Ligases ◽

Cushing's Syndrome ◽

Skeletal Muscle Atrophy ◽

E3 Ubiquitin Ligases ◽

Sprague Dawley ◽

Muscle Weight ◽

Forkhead Box

Cushing’s syndrome is caused by overproduction of the adrenocorticotropic hormone (ACTH), which stimulates the adrenal grand to make cortisol. Skeletal muscle wasting occurs in pathophysiological response to Cushing’s syndrome. The forkhead box (FOX) protein family has been implicated as a key regulator of muscle loss under conditions such as diabetes and sepsis. However, the mechanistic role of the FOXO family in ACTH-induced muscle atrophy is not understood. We hypothesized that FOXO3a plays a role in muscle atrophy through expression of the E3 ubiquitin ligases, muscle RING finger protein-1 (MuRF-1), and atrogin-1 in Cushing’s syndrome. For establishment of a Cushing’s syndrome animal model, Sprague-Dawley rats were implanted with osmotic minipumps containing ACTH (40 ng·kg−1·day−1). ACTH infusion significantly reduced muscle weight. In ACTH-infused rats, MuRF-1, atrogin-1, and FOXO3a were upregulated and the FOXO3a promoter was targeted by the glucocorticoid receptor (GR). Transcriptional activity and expression of FOXO3a were significantly decreased by the GR antagonist RU486. Treatment with RU486 reduced MuRF-1 and atrogin-1 expression in accordance with reduced enrichment of FOXO3a and Pol II on the promoters. Knockdown of FOXO3a prevented dexamethasone-induced MuRF-1 and atrogin-1 expression. These results indicate that FOXO3a plays a role in muscle atrophy through expression of MuRF-1 and atrogin-1 in Cushing’s syndrome.

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Muscle protection during hibernation of Daurian ground squirrels (Spermophilus dauricus): role of atrogin-1, MuRF1, and fiber-type transition

Canadian Journal of Zoology ◽

10.1139/cjz-2015-0242 ◽

2016 ◽

Vol 94 (9) ◽

pp. 619-629 ◽

Cited By ~ 6

Author(s):

Kai Dang ◽

Ban Feng ◽

Yunfang Gao ◽

Naifei Hu ◽

Shanfeng Jiang ◽

...

Keyword(s):

Skeletal Muscle ◽

Mrna Expression ◽

Muscle Atrophy ◽

Hind Limb ◽

Fiber Type ◽

Ground Squirrels ◽

Skeletal Muscle Atrophy ◽

Type I ◽

Protective Mechanisms ◽

Edl Muscle

We investigated the mechanism of protection from skeletal muscle atrophy in the hind limb extensor digitorum longus (EDL) muscle of hibernating Daurian ground squirrels (Spermophilus dauricus Brandt, 1843). The effects of unrestrained hibernation and 14 day hind limb unloading (HLU) on EDL were studied in three seasons (summer, autumn, and winter). Atrogin-1 and MuRF1 mRNA skeletal muscle expression, wet muscle mass, and muscle to body mass ratios were unchanged during hibernation in all three seasons. EDL mass measurements decreased following HLU and atrogin-1 and MuRF1 mRNA expression increased. In summer, atrogin-1 and MuRF1 mRNA expression increased by 85% and 75%, respectively; in autumn, by 95% and 69%, respectively; and in winter, by 91% and 65%, respectively (P < 0.05). In the HLU group, microscopic skeletal muscle changes were present, including a reduction in the percentage of type-I skeletal muscle fibers. Fat storage in Daurian ground squirrels and a shorter photoperiod during hibernation did not affect the protective mechanisms that prevented skeletal muscle atrophy. The results of this study suggest that the stable expression of atrogin-1 and MuRF1 and the transition from fast glycolytic fibers to slow oxidative fibers are associated with a lack of skeletal muscle atrophy in the hibernating Daurian ground squirrel.

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