Modulation of responses of feline γ‐motoneurones by noradrenaline, tizanidine and clonidine

Exaggeration of stretch reflexes after injuries of the nervous system might be due to several factors. Hyperactivity of fusimotor neurones, and therefore abnormally strong responses of muscle spindle afferents, were repeatedly considered as one of these factors (see e.g. Hagbarth et al. 1973; Burke, 1980, 1983; Noth, 1991; Pierrot-Deseilligny et al. 1993). However, when responses of primary afferents to muscle stretches were compared, no evidence was found for a consistently stronger fusimotor drive in spastic patients than in healthy subjects (see Hagbarth et al. 1973). There has therefore been a tendency to consider that fusimotor neurones do not contribute to spasticity in a significant way (see Pierrot-Deseilligny et al. 1993). Some recent observations might nevertheless revive this possibility. Particularly relevant are observations that the noradrenaline (NA) agonist clonidine not only weakens stretch reflexes (in spastic patients: Stewart et al. 1991; Nance, 1994; B. Bussel, personal communication; in animals: K. Pearson, personal communication) but also depresses the dynamic sensitivity of muscle spindle afferents (Bennett et al. 1996). This last effect was thought to be caused by a reduction in the fusimotor drive. However, there are several ways of reducing the dynamic sensitivity. Clonidine might depress activity of γd- or βd-fusimotor neurones, it might act on these neurones themselves, or it might depress activity of neurones which provide input to them (e.g. those mediating the flexion/ extension reflexes, Anden et al. 1966). If the antispastic actions of the NA agonists clonidine and tizanidine (see Emre, 1993), and L-β-3,4-dihydroxyphenylalanine (l-DOPA, the NA precursor; Eriksson et al. 1996) involve depression at the level of γ-motoneurones, one might reconsider a contribution by these neurones to the exaggerated stretch reflexes in spastic patients. Even if the background activity of fusimotor neurones is similar in spastic and healthy subjects, reflex activation of these neurones might be more effective in spastic patients, as pointed out by Burke (1980, 1983). γ-Motoneurones might be abnormally strongly activated by group II muscle afferents which are one of the main sources of peripheral input to them (see Appelberg et al. 1983; Gladden et al. 1998). β-Motoneurones should be as strongly activated by group II afferents as α-motoneurones (Lundberg et al. 1987a, b). Both γ- and β-motoneurones might therefore induce more potent responses of muscle spindle primary and secondary afferents than normal. The primaries and secondaries would in turn contribute to a more effective excitation of α- and β-motoneurones, primaries mainly by their direct actions and secondaries via interneuronal pathways (see Eriksson et al. 1996), but also directly (Kirkwood & Sears, 1974; Stauffer et al. 1976; Munson et al. 1982). The secondaries might in addition increase the already high excitability of γ-motoneurones, acting either via interneuronal pathways or directly, as indicated in the companion paper (Gladden et al. 1998). The present study was undertaken to extend previous observations on the effects of systemically applied noradrenergic agents on γ-motoneurones (Grillner et al. 1967; Bergmans & Grillner, 1968; Grillner, 1969; Bennett et al. 1996) by investigating whether these agents act directly on them. To this end, we analysed the modulatory actions of NA and its two agonists on responses of γ-motoneurones, either evoked by group II muscle afferents or by other neurones, the latter expressed as tonic background activity. Local actions of NA and tizanidine (which are particularly effective in depressing synaptic transmission from group II muscle afferents to other neurones (Bras et al. 1990)) were investigated following their ionophoretic application close to γ-motoneurones. Actions of clonidine were investigated after its systemic application, as in the study of effects of clonidine on responses of muscle spindle afferents (Bennett et al. 1996). In both approaches the effects were estimated using records from single γ-motoneurones. A preliminary report of this work has been published (Jankowska et al. 1997)