Adrenalectomy attenuates hyperalgesia but does not regulate muscle wasting in a female rat model of fibromyalgia

• Published in: Clinical and experimental pharmacology & physiology 2024-03, Vol.51 (3), p.e13837-n/a
• Main Authors: Costa, Daniely Messias, Silva, Raquel Prado, Cruz‐Filho, João, Santos, Tatiane, Anjos‐Santos, Hevely Catharine, Lucca Jr, Waldecy, Kettelhut, Ísis, Navegantes, Luiz Carlos, Souza, Patrícia Rodrigues Marques, Camargo, Enilton Aparecido, Lauton‐Santos, Sandra, Badauê‐Passos Jr, Daniel, Mecawi, André Souza, DeSantana, Josimari Melo, Lustrino, Danilo
• Format: Article
• Language: English
• Subjects: Adrenal glands; Adrenalectomy; AKT protein; Animals; Atrophy; Attenuation; Corticosterone; Female; Females; Fibromyalgia; Fibromyalgia - complications; Fibromyalgia - drug therapy; Fibromyalgia - pathology; Gastrocnemius muscle; Glucocorticoids; Hyperalgesia; Hyperalgesia - drug therapy; Hypothalamo-Hypophyseal System - metabolism; Hypothalamo-Hypophyseal System - pathology; Hypothalamus; Kinases; Mechanical properties; Motor task performance; muscle protein turnover; Muscle, Skeletal - metabolism; Muscles; Muscular Atrophy - pathology; Musculoskeletal system; Pain perception; pH effects; Pituitary; Pituitary-Adrenal System - metabolism; Pituitary-Adrenal System - pathology; Proteasomes; Protein biosynthesis; Protein synthesis; Protein turnover; Proteins; Proteolysis; Rats; Saline Solution - pharmacology; Skeletal muscle; skeletal muscle mass; stress‐related axis
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/1440-1681.13837

Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5‐day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross‐sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy‐related gene (muscle RING‐finger protein‐1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline‐injected animals. The data suggests that the stress‐related hypothalamic–pituitary–adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms.