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Botulinum neurotoxin injections for muscle-based (dystonia and spasticity) and non-muscle-based (neuropathic pain) pain disorders: a meta-analytic study

  • Neurology and Preclinical Neurological Studies - Original Article
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Abstract

Apart from the known efficacy of Botulinum Neurotoxin Type A (BoNT/A) in hyperactive striated and smooth muscles, different pain states have become potential targets of toxin effects. This present study determined the comparative toxin effectiveness in pain reduction among those patients injected with BoNT/A in muscle-based and in non-muscle-based conditions. Randomized controlled trials (RCTs) on the effect of BoNT/A on selected pain conditions were included. The conditions were spasticity and dystonia for muscle-based pain. For non-muscle-based pain, conditions included were painful diabetic neuropathy (PDN), post-herpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), and spinal cord injury (SCI). In view of possibly differing pathophysiology, myofascial pain, temporomandibular joint (TMJ), other joint or tendon pains, cervicogenic and lumbar pains, migraine and visceral pain syndromes were excluded. Standardized mean difference was used as the effect measure and computed with STATA. 25 RCTs were analyzed. Pooled estimates showed significantly lower pain score in the Treatment group (z = 5.23, p < 0.01, 95% CI = – 0.75, – 0.34). Subgroup analyses showed that BoNT/A significantly reduced both muscle-based (z = 3.78, p < 0.01, 95% CI = – 0.72, – 0.23) and non-muscle-based (z = 3.37, p = 0.001, 95% CI = – 1.00, – 0.27) pain. Meta-regression using four covariates namely dosage, route, frequency and duration was done which revealed that dosage significantly affects standardized mean differences, while the other three covariates were insignificant. The joint F-test was found to be insignificant (p value = 0.1182). The application of the model with these covariates does not significantly explain the derived heterogeneity of standardized mean differences. In conclusion, BoNT/A can be effectively used in muscle-based and non-muscle-based pain disorders. We detected no difference between the presence and magnitude of pain relief favoring muscle-based compared to non-muscle-based pain. Thus, we cannot say whether or not there might be independent mechanisms of toxin-induced pain relief for pain generated from either muscle or nerve hyperactivity.

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Acknowledgements

Dr. Kanovsky was supported by the MZCR Institutional support—conceptual development of research organization—DRO (FNOL, 00098892) 2018.

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Authors and Affiliations

  1. Department of Neurology and Psychiatry, University of Santo Tomas Hospital, España, 1008, Manila, Philippines

    Paula Ruth L. Siongco & Raymond L. Rosales

  2. Faculty of Medicine and Surgery, University of Santo Tomas, España, 1008, Manila, Philippines

    Raymond L. Rosales

  3. Department of Neurology, The Walton Centre NHS Foundation Trust, Lower Lamce, Fazakerley, Liverpool, L9 7LJ, UK

    Austen Peter Moore

  4. Zentrum für AnästhesiologieIntensivmedizinSchmerzmedizin and Palliativmedizin, Benedictus Krankenhaus Tutzing, Tutzing, Germany

    Rainer Freynhagen

  5. Klinik für Anästhesiologie, Technische Universität München, München, Germany

    Rainer Freynhagen

  6. Clinical Neurophysiology, Department of Neurology and Geriatrics, Kagoshima University Hospital, Sakuragaoka, Kagoshima, Japan

    Kimiyoshi Arimura

  7. Department of Neurology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, Czech Republic

    Petr Kanovsky

  8. Department of Neurology, Tokushima University, Shinkuracho, Tokushima, Japan

    Ryuji Kaji

  9. Center for Neurological Restoration, Neurological Institute, Cleveland Clinic, Euclid Avenue, Cleveland, OH, USA

    Hubert H. Fernandez

  10. Movement Disorders Section, Department of Neurology, Hannover Medical School, Hannover, Germany

    Dirk Dressler

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  1. Paula Ruth L. Siongco
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  2. Raymond L. Rosales
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  5. Kimiyoshi Arimura
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  6. Petr Kanovsky
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  9. Dirk Dressler
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Correspondence to Paula Ruth L. Siongco.

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Siongco, P.R.L., Rosales, R.L., Moore, A.P. et al. Botulinum neurotoxin injections for muscle-based (dystonia and spasticity) and non-muscle-based (neuropathic pain) pain disorders: a meta-analytic study. J Neural Transm 127, 935–951 (2020). https://doi.org/10.1007/s00702-020-02163-5

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