Exp Brain Res (2003) 148:509–514 DOI 10.1007/s00221-002-1313-4 RESEARCH ARTICLE O. RØmy-NØris · P. Denys · O. Daniel · H. Barbeau · B. Bussel Effect of intrathecal clonidine on group I and group II oligosynaptic excitation in paraplegics Received: 29 April 2002 / Accepted: 4 October 2002 / Published online: 22 November 2002  Springer-Verlag 2002 Abstract We investigated the possibility that a change in transmission in group II pathways contributes to the spasticity of patients with spinal lesions. Thirteen patients were tested by measuring the quadriceps stretch reflex (Ashworth scale), the threshold of the quadriceps H reflex, and the oligosynaptic facilitation of the quadriceps H reflex elicited by volleys to groups I and II afferents in the common peroneal nerve (CPN). All these tests were performed before and after intrathecal injection of clonidine (60 g). Early group I CPN-induced excitations occurred in 13 patients, and late group II CPN-induced excitations in 12. Both facilitations were, on average, significantly greater than those reported for normal subjects, but these increases were not correlated with the clinically assessed spasticity. Clonidine caused a constant, prolonged and dramatic decrease in spasticity, but did not alter the threshold of the quadriceps H reflex. CPN-induced group I and group II non-monosynaptic excitations of quadriceps motoneurones were significant- ly decreased, although they did not return to normal values. These results provide a further indication that group II pathways gives rise to the heteronymous late CPN-induced excitation. The pathophysiological role of a change in transmission in group II pathways in spasticity is discussed. Keywords Spasticity · Group II excitation · Intrathecal · Clonidine · Human Introduction Both primary and secondary muscle spindle endings (innervating group Ia and group II muscle afferents, respectively) are excited by muscle stretch (see Matthews 1933). However, the involvement of group II pathways in the exaggeration of the stretch reflex characteristic of spasticity has not been discussed because they were considered to be part of the flexor reflex afferent system. This pathway mainly inhibits extensor motoneurones in low-spinal cat preparations. However, alternative path- ways have been found using low pontine lesions in decerebrate animals (Holmqvist and Lundberg 1961), and large group II excitatory post-synaptic potentials (EPSPs) are more common in extensor motoneurones in unanaes- thetised high-lesion (Wilson and Kato 1965) and low- lesion (Hongo and Petterson 1988) spinal cats. Recent studies on humans have demonstrated that the medium- latency response evoked by stretching ankle and foot muscles is transmitted through spinal group II pathways (Schieppati and Nardone 1997, 1999; Grey et al. 2001). Human spasticity is currently treated with oral norad- renergic drugs such as tizanidine and clonidine, both of which are a 2 noradrenergic (NA) agonists. Although it has been claimed that the antispastic action of tizanidine is supraspinal (Palmeri and Wiesendanger 1990), two reasons have led us to investigate the spinal effects of intrathecally administered clonidine on spasticity. Firstly, monoaminergic agonists, which do not depress the oligosynaptic actions of group I afferents, presynaptically inhibit the transmission of group II volleys in the cat spinal cord (see Jankowska 1992). Secondly, the NA agonist tizanidine decreases medium-latency stretch re- sponses in normal human subjects (Corna et al. 1995), and a NA precursor (l-DOPA) suppresses knee jerk reflexes in completely paraplegic patients (Eriksson et al. 1996), presumably through the selective inhibition of group II volleys. We have previously shown that intrathecal clonidine decreases spasticity and polysynaptic flexor spinal reflex- es in subjects with spinal lesions, while not altering the O. RØmy-NØris ( ) ) · P. Denys · O. Daniel · H. Barbeau · B. Bussel Service de RØØducation Neurologique and INSERM U483, Hôpital Raymond PoincarØ Garches, France e-mail: oremyneris@hopale.com Fax: +33-321-893140 Present address: O. RØmy-NØris, Centre Jacques CalvØ, Groupe Hopale, 72 esplanade Parmentier, 62608 Berck sur Mer, France Present address: H. Barbeau, McGill University, MontrØal, Canada