Table 3.
Preclinical studies promoting inhibitory tone for SCI-spasticity
| Approach and route | SCI model | Mechanism and conclusion | |
|---|---|---|---|
| Reducing hyperexcitability | |||
| Riluzole (i.p.) | Female SD rats (sacral spinal transection) | Can inhibit some but not aspects of spasticity in tail muscle by inhibiting glutamate release [158] | |
| GABAergic drugs | |||
| Baclofen | Female SD rats (complete transection) | GABAB agonist blocks spasticity in the rats by the same presynaptic mechanisms proposed in humans [159] | |
| Gabapentin (i.p.) | Female Wistar rats (complete transection) | Attenuation of muscular spasticity and autonomic dysreflexia by inhibiting glutamatergic transmission [160] | |
| Female SD rats (spinal transection) | Reduces both the behavioral and electrophysiological manifestations of SCI-induced spasticity by inhibiting glutamatergic transmission [135] | ||
| Calcium channel blockers | |||
| Nimodipine (s.c.) | Vglut2Cre mouse, HoxBCre mouse (complete transection) | Acute treatment completely prevented development of spasticity by blocking L-type calcium channels [161] | |
| Female SD rats (contusion injury) | Long-term treatment improved locomotion, pain behavior, spasticity symptoms by blocking L-type calcium channels [125] | ||
| KCC2 cotransporter enhancer | |||
| Prochlorperazine (i.v.) | Female Wistar rats (spinal cord transection) | Restoring reciprocal inhibition rescuing KCC2 downregulation rrelieves spasticity equivalent to baclofen [133] | |
| Cell therapy | |||
| Human spinal GABA neurons (intraspinal) | Male SD rats (contusion) | Alleviation of spasticity like response suggesting integration of GABA neurons into local neural circuit [130] | |
| Human neural stem cells [NSI-566RSCs] (intraspinal) | Female SD rats (spinal compression model) | Development of putative GABAergic synapses between grafted and host neurons thus ameliorating spasticity, normalization in thermal and tactile pain threshold [131] | |
SCI, spinal cord injury; i.p., intraperitoneal; SD, sprague Dawley; GABA, gamma-aminobutyric acid; s.c., subcutaneous; KCC2, K+-Cl- cotransporter isoform 2; i.v., intravenous.