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Botulinum toxin for the treatment of pain?
Scandinavian Journal of Pain 2 (2011) 24
Contents lists available at ScienceDirect
Scandinavian Journal of Pain journal homepage: www.ScandinavianJournalPain.com
Editorial comment
Botulinum toxin for the treatment of pain? Nanna Brix Finnerup ∗ , Troels Staehelin Jensen Danish Pain Research Center, Aarhus University, Aarhus, Denmark
Myofascial pain syndrome is a common non-articular local musculoskeletal pain syndrome. The syndrome is characterized by myofascial trigger points, which are tender when stimulated and may give rise to somatic referred pain [1]. The pain quality is often dull and achy, and treatment usually involves physical therapy [1]. Botulinum toxin (BoNT), the neurotoxic protein produced by the bacterium clostridium botulinum, is used for an increasing number of indications. Its therapeutic use includes indications like dystonia, spasticity, strabismus, blepharospasms, neurogenic detrusor overactivity, hyperhidrosis, and cosmetic use for wrinkles. Because botulinum toxin type A (BTX-A) blocks neuromuscular transmission, it has also been used to treat pain related to muscle spasms or muscle tension. In addition, a direct antinociceptive action is suggested, both peripherally and centrally, e.g. through the calcitonin gene-related peptide (CGRP), substance P, and the protein kinase C of the transient receptor potential vanilloid 1 (TRPV1) receptor [2]. In this issue of the Scandinavian Journal of Pain, Müller-Schwefe et al. [3] report the results of a trial of the effect of Dysport® (BoNT) for the treatment of myofascial back pain. The authors are to be commended for taking on the task of performing this large investigator-initiated, multi-centre randomized trial. A total of 202 patients were randomized to receive a low, medium, or high dose of Dysport® . Treatment was administered by injections at four trigger points. The mean pain reduction from baseline to week 6 on pain at rest and on movement was 20–25%, with no difference among the three doses. There was also a reduction in pain disability, which did not differ among the groups. The treatment was well tolerated, and adverse effects were not correlated to dose. The most common adverse effect was influenza-like symptoms. Does this study then show that there is an analgesic effect associated with BoNT? Unfortunately not. If the study had found a dose-depending pain-relieving effect of Dysport, it would strongly suggest an effect in myofascial back pain. However, due to the lack of such findings, the study provides no information on the possible pain-relieving effect of BoNT in myofascial back pain, since it did not include a placebo control. Particularly given the low pain intensity scores at rest (mean 2.2, NRS 0-10) and on movement (mean 2.6),
DOI of refers to article:10.1016/j.sjpain.2010.11.002. ∗ Corresponding author at: Danish Pain Research Center, Aarhus University Hospital, Noerrebrogade 44, Building 1A, DK-8000 Aarhus C, Denmark. Tel.: +45 8949 3455, fax: +45 8949 3269. E-mail address: fi[email protected] (N.B. Finnerup).
the inclusion of patients with pain lasting down to 3 weeks, and allowance of concomitant physiotherapy, regression towards the mean and placebo responses may easily explain the change in pain score found in the study. The study does, however, provide some information about what doses to use in future placebo-controlled trials of Dysport® , since doses of 80 and 120 units per trigger point did not result in an increased pain-relieving effect compared to 60 units in this study of four-trigger-point injections. Previous studies on the effect of BoNT in various musculoskeletal pain conditions including neck, back and shoulder pain, and temporomandibular and whiplash-associated disorders have shown conflicting results [4,5], and it has been concluded that larger placebo-controlled studies are needed to establish the role of BoNT in musculoskeletal pain. It is possible that subgroups of patients with musculoskeletal pain may respond, but so far there are no data to suggest which patients may respond. Enriched enrollment studies would be useful in demonstrating such effect. Other types of pain for which BoNT may be beneficial include migraine, tension-type headache, and neuropathic pain [4], but also for these various pain conditions large placebo-controlled studies are needed to evaluate its efficacy. In conclusion, given the inconsistent results from randomized placebo-controlled trials in musculoskeletal pain [4,5], there is so far not sufficient evidence to recommend BoNT for clinical use in musculoskeletal pain. Given the cost of BoNT treatment, it is also reasonable to require that the effect of BoNT is superior not only to placebo but also to less costly treatment approaches. References [1] Graff-Radford SB. Myofascial pain: diagnosis and management. Curr Pain Headache Rep 2004;8:463–7. [2] Aoki KR. Future aspects of botulinum neurotoxins. J Neural Transm 2008;115:567–73. [3] Müller-Schwefe GHH, Ûberall MA. Dysport® for the treatment of myofascial back pain: results from an open-label, phase II, randomized, multicenter, doseranging study. Scand J Pain 2011;2:25–33. [4] Qerama E, Fuglsang-Frederiksen A, Jensen TS. The role of botulinum toxin in management of pain: an evidence-based review. Curr Opin Anaesthesiol 2010;23:602–10. [5] Langevin P, Lowcock J, Weber J, Nolan M, Gross AR, Peloso PM, Roberts J, Graham N, Goldsmith CH, Burnie SJ, Haines T. Botulinum toxin intramuscular injections for neck pain: a systematic review and metaanalysis. J Rheumatol 2010; (December) [Epub].
1877-8860/$ – see front matter © 2010 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.sjpain.2010.12.002
Contents lists available at ScienceDirect
Scandinavian Journal of Pain journal homepage: www.ScandinavianJournalPain.com
Editorial comment
Botulinum toxin for the treatment of pain? Nanna Brix Finnerup ∗ , Troels Staehelin Jensen Danish Pain Research Center, Aarhus University, Aarhus, Denmark
Myofascial pain syndrome is a common non-articular local musculoskeletal pain syndrome. The syndrome is characterized by myofascial trigger points, which are tender when stimulated and may give rise to somatic referred pain [1]. The pain quality is often dull and achy, and treatment usually involves physical therapy [1]. Botulinum toxin (BoNT), the neurotoxic protein produced by the bacterium clostridium botulinum, is used for an increasing number of indications. Its therapeutic use includes indications like dystonia, spasticity, strabismus, blepharospasms, neurogenic detrusor overactivity, hyperhidrosis, and cosmetic use for wrinkles. Because botulinum toxin type A (BTX-A) blocks neuromuscular transmission, it has also been used to treat pain related to muscle spasms or muscle tension. In addition, a direct antinociceptive action is suggested, both peripherally and centrally, e.g. through the calcitonin gene-related peptide (CGRP), substance P, and the protein kinase C of the transient receptor potential vanilloid 1 (TRPV1) receptor [2]. In this issue of the Scandinavian Journal of Pain, Müller-Schwefe et al. [3] report the results of a trial of the effect of Dysport® (BoNT) for the treatment of myofascial back pain. The authors are to be commended for taking on the task of performing this large investigator-initiated, multi-centre randomized trial. A total of 202 patients were randomized to receive a low, medium, or high dose of Dysport® . Treatment was administered by injections at four trigger points. The mean pain reduction from baseline to week 6 on pain at rest and on movement was 20–25%, with no difference among the three doses. There was also a reduction in pain disability, which did not differ among the groups. The treatment was well tolerated, and adverse effects were not correlated to dose. The most common adverse effect was influenza-like symptoms. Does this study then show that there is an analgesic effect associated with BoNT? Unfortunately not. If the study had found a dose-depending pain-relieving effect of Dysport, it would strongly suggest an effect in myofascial back pain. However, due to the lack of such findings, the study provides no information on the possible pain-relieving effect of BoNT in myofascial back pain, since it did not include a placebo control. Particularly given the low pain intensity scores at rest (mean 2.2, NRS 0-10) and on movement (mean 2.6),
DOI of refers to article:10.1016/j.sjpain.2010.11.002. ∗ Corresponding author at: Danish Pain Research Center, Aarhus University Hospital, Noerrebrogade 44, Building 1A, DK-8000 Aarhus C, Denmark. Tel.: +45 8949 3455, fax: +45 8949 3269. E-mail address: fi[email protected] (N.B. Finnerup).
the inclusion of patients with pain lasting down to 3 weeks, and allowance of concomitant physiotherapy, regression towards the mean and placebo responses may easily explain the change in pain score found in the study. The study does, however, provide some information about what doses to use in future placebo-controlled trials of Dysport® , since doses of 80 and 120 units per trigger point did not result in an increased pain-relieving effect compared to 60 units in this study of four-trigger-point injections. Previous studies on the effect of BoNT in various musculoskeletal pain conditions including neck, back and shoulder pain, and temporomandibular and whiplash-associated disorders have shown conflicting results [4,5], and it has been concluded that larger placebo-controlled studies are needed to establish the role of BoNT in musculoskeletal pain. It is possible that subgroups of patients with musculoskeletal pain may respond, but so far there are no data to suggest which patients may respond. Enriched enrollment studies would be useful in demonstrating such effect. Other types of pain for which BoNT may be beneficial include migraine, tension-type headache, and neuropathic pain [4], but also for these various pain conditions large placebo-controlled studies are needed to evaluate its efficacy. In conclusion, given the inconsistent results from randomized placebo-controlled trials in musculoskeletal pain [4,5], there is so far not sufficient evidence to recommend BoNT for clinical use in musculoskeletal pain. Given the cost of BoNT treatment, it is also reasonable to require that the effect of BoNT is superior not only to placebo but also to less costly treatment approaches. References [1] Graff-Radford SB. Myofascial pain: diagnosis and management. Curr Pain Headache Rep 2004;8:463–7. [2] Aoki KR. Future aspects of botulinum neurotoxins. J Neural Transm 2008;115:567–73. [3] Müller-Schwefe GHH, Ûberall MA. Dysport® for the treatment of myofascial back pain: results from an open-label, phase II, randomized, multicenter, doseranging study. Scand J Pain 2011;2:25–33. [4] Qerama E, Fuglsang-Frederiksen A, Jensen TS. The role of botulinum toxin in management of pain: an evidence-based review. Curr Opin Anaesthesiol 2010;23:602–10. [5] Langevin P, Lowcock J, Weber J, Nolan M, Gross AR, Peloso PM, Roberts J, Graham N, Goldsmith CH, Burnie SJ, Haines T. Botulinum toxin intramuscular injections for neck pain: a systematic review and metaanalysis. J Rheumatol 2010; (December) [Epub].
1877-8860/$ – see front matter © 2010 Scandinavian Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.sjpain.2010.12.002