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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2004 Jan;75(1):130–135.

Modulation of the transmission in group II heteronymous pathways by tizanidine in spastic hemiplegic patients

E Maupas 1, P Marque 1, C Roques 1, M Simonetta-Moreau 1
PMCID: PMC1757451  PMID: 14707322

Abstract

Objective: To investigate the effect of tizanidine (an α2 noradrenergic agonist) on transmission in the interneuronal pathway coactivated by group I and group II afferents in post-stroke patients with spastic hemiplegia.

Methods: Early and late facilitation of the quadriceps H reflex elicited in the common peroneal nerve—attributed to non-monosynaptic group I and group II excitation, respectively—was investigated in 14 spastic hemiplegic patients. All received a single dose of tizanidine (150 µg/kg) or placebo in randomised order at 10 day intervals. Repeated measurements were made at baseline (T0), 45–90 min, and 120 min after drug intake. Spasticity was assessed by modified Ashworth score in the quadriceps muscle and by a leg tone score calculated by the sum of the modified Ashworth score in five muscle groups.

Results: On the spastic side a decrease in late group II and, to a lesser extent, early group I common peroneal nerve induced quadriceps H reflex facilitation occurred with tizanidine (group II, mean (SEM) difference T0–T90: 34.3 (10.2)%, p<0.001; group I, T0–T120: 19.8 (9)%, p<0.05), but not with placebo (group II, difference T0–T90: 12.5 (8)%, NS; group I, T0–T120: 3.2 (7)%, NS). Tizanidine but not placebo decreased the quadriceps muscle and global lower limb Ashworth scores (2.9 (0.2) to 1.9 (0.3), p<0.001; and 12 (0.7) to 9.5 (0.8), p<0.0001, respectively).

Conclusions: Enhancement of group II–group I facilitation of the quadriceps motor neurones on the spastic side of hemiplegic patients is modulated by α2 noradrenergic agonists. This strengthens the view that late facilitation of quadriceps motor neurones is mediated by group II afferents and suggests that group II pathways may be involved in lower limb spasticity.

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Selected References

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  1. Bras H., Jankowska E., Noga B., Skoog B. Comparison of Effects of Various Types of NA and 5-HT Agonists on Transmission from Group II Muscle Afferents in the Cat. Eur J Neurosci. 1990;2(12):1029–1039. doi: 10.1111/j.1460-9568.1990.tb00015.x. [DOI] [PubMed] [Google Scholar]
  2. Chaix Y., Marque P., Meunier S., Pierrot-Deseilligny E., Simonetta-Moreau M. Further evidence for non-monosynaptic group I excitation of motoneurones in the human lower limb. Exp Brain Res. 1997 Jun;115(1):35–46. doi: 10.1007/pl00005683. [DOI] [PubMed] [Google Scholar]
  3. Conway B. A., Hultborn H., Kiehn O., Mintz I. Plateau potentials in alpha-motoneurones induced by intravenous injection of L-dopa and clonidine in the spinal cat. J Physiol. 1988 Nov;405:369–384. doi: 10.1113/jphysiol.1988.sp017337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Corna S., Grasso M., Nardone A., Schieppati M. Selective depression of medium-latency leg and foot muscle responses to stretch by an alpha 2-agonist in humans. J Physiol. 1995 May 1;484(Pt 3):803–809. doi: 10.1113/jphysiol.1995.sp020705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davies H. E., Edgley S. A. Inputs to group II-activated midlumbar interneurones from descending motor pathways in the cat. J Physiol. 1994 Sep 15;479(Pt 3):463–473. doi: 10.1113/jphysiol.1994.sp020310. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davies J. Selective depression of synaptic transmission of spinal neurones in the cat by a new centrally acting muscle relaxant, 5-chloro-4-(2-imidazolin-2-yl-amino)-2, 1, 3-benzothiodazole (DS103-282). Br J Pharmacol. 1982 Jul;76(3):473–481. doi: 10.1111/j.1476-5381.1982.tb09242.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. HODES R., DEMENT W. C. DEPRESSION OF ELECTRICALLY INDUCED REFLEXES ("H-REFLEXES") IN MAN DURING LOW VOLTAGE EEG "SLEEP". Electroencephalogr Clin Neurophysiol. 1964 Dec;17:617–629. doi: 10.1016/0013-4694(64)90229-9. [DOI] [PubMed] [Google Scholar]
  8. Hagbarth K. E., Wallin G., Löfstedt L. Muscle spindle responses to stretch in normal and spastic subjects. Scand J Rehabil Med. 1973;5(4):156–159. [PubMed] [Google Scholar]
  9. Hammar Ingela, Jankowska Elzbieta. Modulatory effects of alpha1-,alpha2-, and beta -receptor agonists on feline spinal interneurons with monosynaptic input from group I muscle afferents. J Neurosci. 2003 Jan 1;23(1):332–338. doi: 10.1523/JNEUROSCI.23-01-00332.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jankowska E., Hammar I., Chojnicka B., Hedén C. H. Effects of monoamines on interneurons in four spinal reflex pathways from group I and/or group II muscle afferents. Eur J Neurosci. 2000 Feb;12(2):701–714. doi: 10.1046/j.1460-9568.2000.00955.x. [DOI] [PubMed] [Google Scholar]
  11. Jankowska E. Interneuronal relay in spinal pathways from proprioceptors. Prog Neurobiol. 1992;38(4):335–378. doi: 10.1016/0301-0082(92)90024-9. [DOI] [PubMed] [Google Scholar]
  12. Knutsson E., Mårtensson A., Gransberg L. Antiparetic and antispastic effects induced by tizanidine in patients with spastic paresis. J Neurol Sci. 1982 Feb;53(2):187–204. doi: 10.1016/0022-510x(82)90005-3. [DOI] [PubMed] [Google Scholar]
  13. Marchand-Pauvert V., Nielsen J. B. Modulation of non-monosynaptic excitation from ankle dorsiflexor afferents to quadriceps motoneurones during human walking. J Physiol. 2002 Jan 15;538(Pt 2):647–657. doi: 10.1113/jphysiol.2001.012675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Marchand-Pauvert V., Simonetta-Moreau M., Pierrot-Deseilligny E. Cortical control of spinal pathways mediating group II excitation to human thigh motoneurones. J Physiol. 1999 May 15;517(Pt 1):301–313. doi: 10.1111/j.1469-7793.1999.0301z.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Marque P., Pierrot-Deseilligny E., Simonetta-Moreau M. Evidence for excitation of the human lower limb motoneurones by group II muscle afferents. Exp Brain Res. 1996 May;109(2):357–360. doi: 10.1007/BF00231793. [DOI] [PubMed] [Google Scholar]
  16. Marque P., Simonetta-Moreau M., Maupas E., Roques C. F. Facilitation of transmission in heteronymous group II pathways in spastic hemiplegic patients. J Neurol Neurosurg Psychiatry. 2001 Jan;70(1):36–42. doi: 10.1136/jnnp.70.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Maxwell D. J., Riddell J. S., Jankowska E. Serotoninergic and noradrenergic axonal contacts associated with premotor interneurons in spinal pathways from group II muscle afferents. Eur J Neurosci. 2000 Apr;12(4):1271–1280. doi: 10.1046/j.1460-9568.2000.00022.x. [DOI] [PubMed] [Google Scholar]
  18. Nance P. W., Bugaresti J., Shellenberger K., Sheremata W., Martinez-Arizala A. Efficacy and safety of tizanidine in the treatment of spasticity in patients with spinal cord injury. North American Tizanidine Study Group. Neurology. 1994 Nov;44(11 Suppl 9):S44–S52. [PubMed] [Google Scholar]
  19. Noga B. R., Bras H., Jankowska E. Transmission from group II muscle afferents is depressed by stimulation of locus coeruleus/subcoeruleus, Kölliker-Fuse and raphe nuclei in the cat. Exp Brain Res. 1992;88(3):502–516. doi: 10.1007/BF00228180. [DOI] [PubMed] [Google Scholar]
  20. O'Dwyer N. J., Ada L., Neilson P. D. Spasticity and muscle contracture following stroke. Brain. 1996 Oct;119(Pt 5):1737–1749. doi: 10.1093/brain/119.5.1737. [DOI] [PubMed] [Google Scholar]
  21. Palmeri A., Wiesendanger M. Concomitant depression of locus coeruleus neurons and of flexor reflexes by an alpha 2-adrenergic agonist in rats: a possible mechanism for an alpha 2-mediated muscle relaxation. Neuroscience. 1990;34(1):177–187. doi: 10.1016/0306-4522(90)90311-q. [DOI] [PubMed] [Google Scholar]
  22. Pivik R. T., Mercier L. Motoneuronal excitability during wakefulness and non-REM sleep: H-reflex recovery function in man. Sleep. 1979 Summer;1(4):357–367. doi: 10.1093/sleep/1.4.357. [DOI] [PubMed] [Google Scholar]
  23. Rémy-Néris O., Denys P., Daniel O., Barbeau H., Bussel B. Effect of intrathecal clonidine on group I and group II oligosynaptic excitation in paraplegics. Exp Brain Res. 2002 Nov 22;148(4):509–514. doi: 10.1007/s00221-002-1313-4. [DOI] [PubMed] [Google Scholar]
  24. Sandrini G., Milanov I., Rossi B., Murri L., Alfonsi E., Moglia A., Nappi G. Effects of sleep on spinal nociceptive reflexes in humans. Sleep. 2001 Feb 1;24(1):13–17. doi: 10.1093/sleep/24.1.13. [DOI] [PubMed] [Google Scholar]
  25. Schieppati M., Nardone A. Medium-latency stretch reflexes of foot and leg muscles analysed by cooling the lower limb in standing humans. J Physiol. 1997 Sep 15;503(Pt 3):691–698. doi: 10.1111/j.1469-7793.1997.691bg.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schieppati M., Nardone A., Siliotto R., Grasso M. Early and late stretch responses of human foot muscles induced by perturbation of stance. Exp Brain Res. 1995;105(3):411–422. doi: 10.1007/BF00233041. [DOI] [PubMed] [Google Scholar]
  27. Simonetta-Moreau M., Marque P., Marchand-Pauvert V., Pierrot-Deseilligny E. The pattern of excitation of human lower limb motoneurones by probable group II muscle afferents. J Physiol. 1999 May 15;517(Pt 1):287–300. doi: 10.1111/j.1469-7793.1999.0287z.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Skoog B. A comparison of the effects of two antispastic drugs, tizanidine and baclofen, on synaptic transmission from muscle spindle afferents to spinal interneurones in cats. Acta Physiol Scand. 1996 Jan;156(1):81–90. doi: 10.1046/j.1365-201X.1996.444159000.x. [DOI] [PubMed] [Google Scholar]
  29. Taittonen M., Räty H., Kirvelä O., Aantaa R., Kanto J. The metabolic effects of oral tizanidine in healthy volunteers. Acta Anaesthesiol Scand. 1995 Jul;39(5):628–632. doi: 10.1111/j.1399-6576.1995.tb04139.x. [DOI] [PubMed] [Google Scholar]
  30. Tanabe M., Kaneko T., Tonohiro T., Iwata N. The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant. Neuropharmacology. 1992 Oct;31(10):1059–1066. doi: 10.1016/0028-3908(92)90108-2. [DOI] [PubMed] [Google Scholar]
  31. Wagstaff A. J., Bryson H. M. Tizanidine. A review of its pharmacology, clinical efficacy and tolerability in the management of spasticity associated with cerebral and spinal disorders. Drugs. 1997 Mar;53(3):435–452. doi: 10.2165/00003495-199753030-00007. [DOI] [PubMed] [Google Scholar]
  32. Wilson L. R., Gandevia S. C., Inglis J. T., Gracies J., Burke D. Muscle spindle activity in the affected upper limb after a unilateral stroke. Brain. 1999 Nov;122(Pt 11):2079–2088. doi: 10.1093/brain/122.11.2079. [DOI] [PubMed] [Google Scholar]

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