title: Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter.
abstract: In experimental and clinical studies, an objective assessment of peripheral muscle resistance represents one of the key elements in determining the efficacy of therapeutic manipulations (e.g. pharmacological, surgical) aimed to ameliorate clinical signs of spasticity and/or rigidity. In the present study, we characterize a newly developed limb flexion resistance meter which permits a semi-automated, computer-controlled measurement of peripheral muscle resistance (PMR) in the lower extremities during a forced flexion of the ankle in the awake rat. Ischemic paraplegia was induced in Sprague-Dawley rats by transient aortic occlusion (10 min) in combination with systemic hypotension (40 mm Hg). After ischemia the presence of spasticity component was determined by the presence of an exaggerated EMG activity recorded from gastrocnemius muscle after nociceptive or proprioceptive afferent activation and by velocity-dependent increase in muscle resistance. Rigidity was induced by high dose (30 mg/kg, i.p.) of morphine. Animals with defined ischemic spasticity or morphine-induced rigidity were then placed into a plastic restrainer and a hind paw attached by a tape to a metal plate driven by a computer-controlled stepping motor equipped with a resistance transducer. The resistance of the ankle to rotation was measured under several testing paradigms: (i) variable degree of ankle flexion (40 degrees, 50 degrees, and 60 degrees), (ii) variable speed/rate of ankle flexion (2, 3, and 4 sec), (iii) the effect of inhalation anesthesia, (iv) the effect of intrathecal baclofen, (v) the effect of dorsal L2-L5 rhizotomy, or (vi) systemic naloxone treatment. In animals with ischemic paraplegia an increased EMG response after peripheral nociceptive or proprioceptive activation was measured. In control animals average muscle resistance was 78 mN and was significantly increased in animals with ischemic spasticity (981-7900 mN). In ischemic-spastic animals a significant increase in measured muscle resistance was seen after increased velocity (4 > 3 > 2 sec) and the angle (40 degrees > 50 degrees > 60 degrees) of the ankle rotation. In spastic animals, deep halothane anesthesia, intrathecal baclofen or dorsal rhizotomy decreased muscle resistance to 39-80% of pretreatment values. Systemic treatment with morphine induced muscle rigidity and corresponding increase in muscle resistance. Morphine-induced increase in muscle resistance was independent on the velocity of the ankle rotation and was reversed by naloxone. These data show that by using this system it is possible to objectively measure the degree of peripheral muscle resistance. The use of this system may represent a simple and effective experimental tool in screening new pharmacological compounds and/or surgical manipulations targeted to modulate spasticity and/or rigidity after a variety of neurological disorders such as spinal cord traumatic or ischemic injury, multiple sclerosis, cerebral palsy, or Parkinson's disease.
authors.affiliation: Anesthesiology Research Laboratory, University of California-San Diego, La Jolla, CA 92093, USA. mmarsala@ucsd.edu
authors.forename: Martin
authors.initials: M
authors.lastname: Marsala
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hefferan
authors.forename: Osamu
authors.initials: O
authors.lastname: Kakinohana
authors.forename: Seiya
authors.initials: S
authors.lastname: Nakamura
authors.forename: Jozef
authors.initials: J
authors.lastname: Marsala
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Tomori
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D002908:Chronic Disease; D004576:Electromyography / Q000295:instrumentation* / Q000379:methods*; D006221:Halothane / Q000494:pharmacology; D007278:Injections, Spinal; D007511:Ischemia / Q000150:complications / Q000175:diagnosis* / Q000503:physiopathology; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009125:Muscle Relaxants, Central / Q000494:pharmacology; D009127:Muscle Rigidity / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy; D018482:Muscle, Skeletal / Q000503:physiopathology; D009294:Narcotics / Q000494:pharmacology; D010264:Paraplegia / Q000175:diagnosis* / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D019051:Rhizotomy; D012815:Signal Processing, Computer-Assisted; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000601:surgery
chemical_list: D018685:Anesthetics, Inhalation; D009125:Muscle Relaxants, Central; D009294:Narcotics; D009020:Morphine; D001418:Baclofen; D006221:Halothane