[Spasticity treatment with spinal morphine or midazolam. In vitro experiments, animal studies and clinical studies on...

Recent pharmacological investigations have support the hypothesis that spinal modulation of nociception as well as motor coordination is related to the activity of spinal interneurons and that certain spinal transmitters are involved in the control of both regulatory systems. Opioids and benzodiazepines, i.e. endorphin- or GABA-induced mechanisms, may be of importance for spinal treatment of spasticity in the near future. In order to clinically evaluate the interactions of these spinal processes we performed in vitro-experiments, animal studies and clinical investigations on the compatibility and antispastic efficacy of spinally administered opiates and benzodiazepines. Preclinical studies on tissue- and CSF-tolerance of different benzodiazepines (pH, tonometry, turbidimetry, histological findings in animals) are in favour of midazolam, a water-soluble compound, which is active against pharmacologically induced spasms in animals (strychnine application in cats with chronical catheterization of the subarachnoid space) after lumbar intrathecal injection. Using an appropriate dosage of intrathecal midazolam selective blockade of spasticity of the hind legs may be demonstrated with integrated EMG. Clinical investigations (neurological assessment using rating scores for spasticity) in 16 patients, including a double-blind comparison of epidural morphine or midazolam, indicate that both drugs are effective against spinal spasticity of different origin. Efficacy of spinally applied agents depends on the severity of spasms and on the duration and extent of systemic pretreatment.