Intrathecal glycine for pain and dystonia in complex regional pain syndrome

Munts, Alexander G.; van der Plas, Anton A.; Voormolen, Joan H.; Marinus, Johan; Teepe-Twiss, Irene M.; Onkenhout, Willem; van Gerven, Joop M.; van Hilten, Jacobus J.

doi:10.1016/j.pain.2009.07.030

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Volume 146, Issue 1 , Pages 199-204, November 2009

Intrathecal glycine for pain and dystonia in complex regional pain syndrome

Alexander G. Munts
- Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
Anton A. van der Plas
- Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
Joan H. Voormolen
- Department of Neurosurgery, Leiden University Medical Center, The Netherlands
Johan Marinus
- Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
Irene M. Teepe-Twiss
- Department of Pharmacy, Leiden University Medical Center, The Netherlands
Willem Onkenhout
- Department of Clinical Chemistry, Leiden University Medical Center, The Netherlands
Joop M. van Gerven
- Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
- Centre for Human Drug Research, Zernikedreef 10, 2333 CL Leiden, The Netherlands
Jacobus J. van Hilten
- Department of Neurology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands
- Corresponding author. Address: Department of Neurology, Leiden University Medical Center, P.O. Box 9600, Albinusdreef 2, 2300 RC Leiden, The Netherlands. Tel.: +31 71 5262134; fax: +31 71 5248253.

Received 9 February 2009; received in revised form 19 July 2009; accepted 23 July 2009. published online 17 August 2009.

Abstract

Since glycinergic neurotransmission plays an important inhibitory role in the processing of sensory and motor information, intrathecal glycine (ITG) administration may be a potential therapy for both pain and movement disorders in patients with complex regional pain syndrome (CRPS). Aims of the current study, which is the first report on ITG in humans, were to evaluate its safety and efficacy. ITG treatment during 4weeks was studied in CRPS patients with dystonia in the period before they received intrathecal baclofen treatment. Twenty patients were assessed and after exclusion of one patient, the remaining 19 patients were randomized in a double-blind placebo-controlled crossover study. Safety was assessed by clinical evaluation, blood examinations and electrocardiograms. Efficacy measures involved pain (numeric rating scale, McGill pain questionnaire), movement disorders (Burke–Fahn–Marsden dystonia rating scale, unified myoclonus rating scale, tremor research group rating scale), activity (Radboud skills questionnaire, walking ability questionnaire), and a clinical global impression (CGI) and patient’s global impression score (PGI). Treatment-emergent adverse events were generally mild to moderate and not different from placebo treatment. During ITG treatment growth hormone levels were slightly increased. Although there was a trend to worsening on the CGI and PGI during ITG treatment, there were no significant differences between ITG and placebo treatment in any of the outcomes. ITG given over 4weeks was ineffective for pain or dystonia in CRPS. Although no serious adverse events occurred, further studies are required to rule out potential neurotoxicity of ITG.