Abstract
Purpose
Botulinum toxin type A (BoNT-A) has been used to treat many disorders related to excessive muscle contraction, but there are few studies evaluating its effects on neuropathic pain. The aim of this study was to evaluate the analgesic effects of BoNT-A in a rat model of neuropathic pain.
Methods
Male Sprague-Dawley rats were prepared by ligating the left L5 and L6 spinal nerves to produce neuropathic pain. Seventy neuropathic rats were randomly assigned into seven groups. Either normal saline or BoNT-A (10, 20, 30 and 40 U·kg-1) was administered to the plantar surface of the affected left hind paw, and BoNT-A (30 and 40 U·kg-1) was administered into the unaffected right paw in order to determine the druginduced systemic effect. Mechanical and cold allodynia were observed at pre-administration, one, three, five, seven and 15 days after drug administration, and were quantified by measuring withdrawal frequencies to stimuli with von Frey filament and 100% acetone, respectively. Rotarod performance was measured to detect drug-induced adverse motor effects.
Results
The mean minimum withdrawal frequencies to mechanical and cold stimuli were 77 ± II and 90 ± 4.5%, 46 ± 5 and 66 ± 7%, 33 ± 7 and 62 ± 7%, 12 ± 2.9 and 54 ± 7.3% with 10, 20, 30 and 40 U·kg-1 BoNT-A respectively (P < 0.05). Doses of 30 and 40 U·kg-1 BoNT-A resulted in reduced rotarod performance time.
Conclusion
We conclude that peripherally administered BoNT-A reduces mechanical and cold allodynia in a rat model of neuropathic pain.
Résumé
Objectif
La toxine botulique de type A sert à traiter de nombreux troubles reliés à la contraction musculaire excessive, mais peu ďétudes ont évalué ses effets sur la douleur neuropathique. Nous voulions évaluer les effets analgésiques de la BoNT-A sur un modèle de douleur neuropathique chez le rat.
Méthode
Les nerfs rachidiens gauches L5 et L6 de rats mâles Sprague-Dawley ont été ligaturés pour produire une douleur neuropathique. Soixante-dix rats ont été randomisés en sept groupes. Une solution salée ou la BoNT-A (10, 20, 30 et 40 U·kg-1) a été administrée sous la surface plantaire de la patte arrière gauche affectée et la BoNT-A (30 et 40 U·kg-1) dans la patte droite intacte pour déterminer ľeffet systémique induit par le médicament. Ľallodynie mécanique et au froid a été observée avant ľadministration du médicament, puis un, trois, cinq, sept et 15 jours après et a été quantifiée par les mesures des fréquences de retrait aux stimuli avec le filament von Frey et 100 % ďacétone, respectivement. La performance au test de la tige tournante a été mesurée pour détecter les effets moteurs indésirables induits par le médicament.
Résultats
La moyenne des fréquences de retrait minimales aux stimuli mécaniques et au froid a été de 77 ± 11 et 90 ± 4,5 %, 46 ± 5 et 66 ± 7 %, 33 ± 7 et 62 ± 7 %, 12 ± 2,9 et 54 ± 7,3 % avec 10, 20, 30 et 40 U·kg-1 de BoNT-A respectivement (P < 0,05). Les doses de 30 et 40 U·kg-1 de BoNT-A ont réduit le temps de performance au test de la tige tournante.
Conclusion
Ľadministration périphérique de BoNT-A réduit ľallodynie mécanique et au froid dans un modèle de douleur neuropathique chez le rat.
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References
Mahant N, Clouston PD, Lorentz IT. The current use of botulinum toxin. J Clin Neurosci 2000; 7: 389–94.
Porta M. A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of myofascial pain syndrome and pain from chronic muscle spasm. Pain 2000; 85: 101–5.
Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain. A randomized, double-blind study. Neurology 2001; 56: 1290–3.
Fishman LM, Anderson C, Rosner B. BOTOX and physical therapy in the treatment of piriformis syndrome. Am J Phys Med Rehabil 2002; 81: 936–42.
Welch MJ, Purkiss JR, Foster KA. Sensitivity of embryonic rat dorsal root ganglia neurons to Clostridium botulinum neurotoxins. Toxicon 2000; 38: 245–58.
Tarabal O, Calderó J, Ribera J, et al. Regulation of motoneuronal calcitonin gene-related peptide (CGRP) during axonal growth and neuromuscular synaptic plasticity induced by botulinum toxin in rats. Eur J Neurosci 1996; 8: 829–36.
Cui M, Khanijou S, Rubino J, Aoki KR Subcutaneous administration of botulinum toxin A reduces formalininduced pain. Pain 2004; 107: 125–33.
roller B, Sycha T, Gustorff B, et al. A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin A. Neurology 2003; 61: 940–4.
Borodic GE, Acquadro MA. The use of botulinum toxin for the treatment of chronic facial pain. J Pain 2002; 3: 21–7.
Klein AW. The therapeutic potential of botulinum toxin. Dermatol Surg 2004; 30: 452–5.
Argoff CE. A focused review on the use of botulinum toxins for neuropathic pain. Clin J Pain 2002; 18(6 Suppl): S177–81.
Bach-Rojecky L, Relja M, Lackovic Z. Botulinum toxin type A in experimental neuropathic pain. J Neural Transm 2005; 112: 215–9.
Kim SH, Chung JM. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992; 50: 355–63.
Jang Y, Kim ES, Park SS, Lee J, Moon DE The suppressive effects of oxcarbazepine on mechanical and cold allodynia in a rat model of neuropathic pain. Anesth Analg 2005; 101: 800–6.
Sloop RR, Cole BA, Escutin RO. Reconstituted botulinum toxin type A does not lose potency in humans if it is refrozen or refrigerated for 2 weeks before use. Neurology 1997; 48: 249–53.
Xie J, Yoon YW, Yom SS, Chung JM. Norepinephrine rekindles mechanical allodynia in sympathectomized neuropathic rat. Analgesia 1995; 1: 107–13.
Attal N, Jazat F, Kayser V, Guilbaud G. Further evidence for ‘pain-related’ behaviours in a model of unilateral peripheral mononeuropathy. Pain 1990; 41: 235–51.
Choi Y, Yoon YW, Na HS, Kim SH, Chung JM Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain 1994; 59: 369–76.
Arnér S, Meyerson BA. Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 1988; 33: 11–23.
Kim SH, Na HS, Sheen K, Chung JM. Effects of sympathectomy on a rat model of peripheral neuropathy. Pain 1993; 55: 85–92.
Wegert S, Ossipov MH, Nichols ML, et al. Differential activities of intrathecal MK-801 or morphine to alter responses to thermal and mechanical stimuli in normal or nerve-injured rats. Pain 1997; 71: 57–64.
Luvisetto S, Rossetto O, Montecucco C, Pavone F. Toxicity of botulinum neurotoxins in central nervous system of mice. Toxicon 2003; 41: 475–81.
Freund B, Schwartz M. Temporal relationship of muscle weakness and pain reduction in subjects treated with botulinum toxin A. J Pain 2003; 4: 159–65.
Jang JH, Nam TS, Paik KS, Leem JW. Involvement of peripherally released substance P and calcitonin generelated peptide in mediating mechanical hyperalgesia in a traumatic neuropathy model of the rat. Neurosci Lett 2004; 360: 129–32.
Jang JH, Kim DW, Nam TS, Paik KS, Leem JW. Peripheral glutamate receptors contribute to mechanical hyperalgesia in a neuropathic pain model of the rat. Neuroscience 2004; 128: 169–76.
Aoki KR. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache 2003; 43(suppl 1): S9–15.
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Park, H.J., Lee, Y., Lee, J. et al. The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain. Can J Anesth 53, 470–477 (2006). https://doi.org/10.1007/BF03022619
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DOI: https://doi.org/10.1007/BF03022619