title: Quantification of the effects of an alpha-2 adrenergic agonist on reflex properties in spinal cord injury using a system identification technique.
abstract: BACKGROUND
  Despite numerous investigations, the impact of tizanidine, an anti-spastic medication, on changes in reflex and muscle mechanical properties in spasticity remains unclear. This study was designed to help us understand the mechanisms of action of tizanidine on spasticity in spinal cord injured subjects with incomplete injury, by quantifying the effects of a single dose of tizanidine on ankle muscle intrinsic and reflex components.
  
  
  METHODS
  A series of perturbations was applied to the spastic ankle joint of twenty-one spinal cord injured subjects, and the resulting torques were recorded. A parallel-cascade system identification method was used to separate intrinsic and reflex torques, and to identify the contribution of these components to dynamic ankle stiffness at different ankle positions, while subjects remained relaxed.
  
  
  RESULTS
  Following administration of a single oral dose of Tizanidine, stretch evoked joint torque at the ankle decreased significantly (p < 0.001) The peak-torque was reduced between 15% and 60% among the spinal cord injured subjects, and the average reduction was 25%. Using systems identification techniques, we found that this reduced torque could be attributed largely to a reduced reflex response, without measurable change in the muscle contribution. Reflex stiffness decreased significantly across a range of joint angles (p < 0.001) after using tizanidine. In contrast, there were no significant changes in intrinsic muscle stiffness after the administration of tizanidine.
  
  
  CONCLUSIONS
  Our findings demonstrate that tizanidine acts to reduce reflex mechanical responses substantially, without inducing comparable changes in intrinsic muscle properties in individuals with spinal cord injury. Thus, the pre-post difference in joint mechanical properties can be attributed to reflex changes alone. From a practical standpoint, use of a single "test" dose of Tizanidine may help clinicians decide whether the drug can helpful in controlling symptoms in particular subjects.
authors.affiliation: Department of Physical Medicine and Rehabilitation, Northwestern University, Chicago, USA. mehdi@northwestern.edu
authors.forename: Mehdi M
authors.initials: MM
authors.lastname: Mirbagheri
authors.forename: David
authors.initials: D
authors.lastname: Chen
authors.forename: W Zev
authors.initials: WZ
authors.lastname: Rymer
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000627:therapeutic use*; D000328:Adult; D000843:Ankle Joint / Q000187:drug effects / Q000503:physiopathology; D003000:Clonidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004548:Elasticity / Q000187:drug effects; D006801:Humans; D009128:Muscle Spasticity / Q000188:drug therapy* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000503:physiopathology; D010812:Physical Stimulation; D016059:Range of Motion, Articular / Q000187:drug effects; D018341:Receptors, Adrenergic, alpha-2; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000503:physiopathology; D019415:Torque
chemical_list: C547768:ADRA2A protein, human; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; C023754:tizanidine; D003000:Clonidine