Physiologic assessment of botulinum toxin effects in the rat larynx.
OBJECTIVE
Botulinum toxin (BT) is a currently used treatment for spasmodic dysphonia (SD) and other related focal dystonias. The goal of this study is to provide a basis for using the rat larynx to objectively assess physiological and histological effects of BT.


METHODS
Dosages and volumes of BT injection were varied and three physiological parameters were measured. These measures included: optical density of PAS-stained laryngeal muscle after electrical stimulation, which is an indirect measure of denervation, spontaneous laryngeal muscle activity, and laryngeal movement.


METHODS
A new microlaryngoscopic technique was developed, which made it possible to observe and manipulate the rat larynx endoscopically. Laryngeal movement and electromyographic (EMG) measures were made prior to injection and 3 days following BT injections of various dosages and volumes. Optical density measures were made 3 days after injection.


RESULTS
Significant reductions in vocal fold motion and spontaneous laryngeal muscle activity as a function of increased BT dosage were observed. In addition, the optical density of PAS-stained laryngeal muscle after electrical stimulation was increased following BT injection. Significant volume effects in optical density were observed in the lateral thyroarytenoid and lateral cricoarytenoid muscles on the contralateral side.


CONCLUSIONS
The rat laryngeal model is suitable for assessing BT effects. In addition, the three physiological variables provided useful and reliable measures of laryngeal function. It is the authors' intention to use the rat laryngeal model to further examine the physiological and histological effects of BT with the goal of developing new methods for the treatment of patients with SD and other focal dystonias.
Division of Otolaryngology--Head and Neck Surgery, University of Wisconsin Medical School, Madison, USA.
K
K
Inagi
N P
NP
Connor
C N
CN
Ford
E
E
Schultz
A A
AA
Rodriquez
D M
DM
Bless
T
T
Pasic
D M
DM
Heisey
D000818:Animals; D018726:Anti-Dyskinesia Agents / Q000494:pharmacology*; D001905:Botulinum Toxins / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004558:Electric Stimulation; D004576:Electromyography; D007273:Injections, Intramuscular; D007821:Laryngeal Muscles / Q000187:drug effects* / Q000502:physiology; D007828:Laryngoscopy; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014827:Vocal Cords / Q000187:drug effects* / Q000502:physiology; D014832:Voice Disorders / Q000188:drug therapy
D018726:Anti-Dyskinesia Agents; D001905:Botulinum Toxins