The Effect of Denervation and Treatment with the ß2-Agonist, Formoterol, on the Masseter Muscles of Growing Sprague Dawley Rats

Aim: To determine the effects of denervation and treatment with the β2-adrenoceptor agonist, formoterol, on the masseter muscle of the rat. Hypothesis and rationale: Muscles in the craniofacial region, particularly the masseter muscle, are often subject to changes in size and strength as a consequence of post-surgical muscle wasting and neuromuscular disorders. These modifications can influence the timing and nature of orthodontic treatment, as well as post-orthodontic relapse. Method: Young (4 week old) male Sprague Dawley rats were randomly assigned to one of four experimental groups: sham, denervated, denervated+β2-agonist, or β2-agonist-only experimental groups. The rats in the denervated groups had their left masseteric nerve sectioned, and for those in the β2 agonist groups, formoterol was injected directly into the left masseter muscle every 3 days, for 8 weeks. Muscle mass, muscle volume and muscle signal intensity (via MRI), muscle fibre Cross-sectional Area (CSA), and protein per mass of muscle were assessed. Results: Surgical denervation of the masseter muscle resulted in a significant decrease in muscle mass, fibre CSA, muscle volume and an increase in MRI muscle signal intensity. These post-surgical changes were largely prevented by administration of formoterol, demonstrating that β2-agonist administration can attenuate denervation-induced atrophy in the masseter muscle. Administration of a β2-agonist alone without surgical denervation led to increases in muscle mass, muscle volume and fibre CSA, findings that are consistent with the well-reported anabolic effects of formoterol. Conclusions: The findings indicate that intramuscular administration of a β2-agonist can attenuate muscle atrophy concomitant with denervation. Such an approach may have clinical application in orthodontics for helping regulate muscle architecture and function in the treatment of orofacial disorders.