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Licensed Unlicensed Requires Authentication Published by De Gruyter March 27, 2019

Pain in cervical dystonia and the antinociceptive effects of botulinum toxin: what is currently known?

  • Michał Marciniec EMAIL logo , Anna Szczepańska-Szerej , Marcin Kulczyński , Klaudia Sapko , Sylwia Popek-Marciniec and Konrad Rejdak

Abstract

Pain is the most common and disabling non-motor symptom in cervical dystonia (CD). Up to 88.9% of patients report pain at some point in the course of the disease. It is still a matter of debate whether CD-related pain originates only from prolonged muscle contraction. Recent data suggest that the alterations of transmission and processing of nociceptive stimuli play a crucial role in pain development. Botulinum toxin (BT) is the first-line therapy for CD. Despite fully elucidated muscle relaxant action, the antinociceptive effect of BT remains unclear and probably exceeds a simple decompression of the nerve fibers due to the reduction in muscle tone. The proposed mechanisms of the antinociceptive action of BT include inhibition of pain mediator release, inhibition of membrane sodium channels, retrograde axonal transport and impact on the other pain pathways. This article summarizes the current knowledge about the antinociceptive properties of BT and the clinical analgesic efficacy in the treatment of CD patients.

References

Albanese, A., Bhatia, K., Bressman, S.B., DeLong, M.R., Fahn, S., Fung, V.S., Hallett, M., Jankovic, J., Jinnah, H.A., Klein, C., et al. (2013a). Phenomenology and classification of dystonia: a consensus update. Mov. Disord. 28, 863–873.10.1002/mds.25475Search in Google Scholar PubMed PubMed Central

Albanese, A., Sorbo, F.D., Comella, C., Jinnah, H.A., Mink, J.W., Post, B., Vidailhet, M., Volkmann, J., Warner, T.T., Leentjens, A.F., et al. (2013b). Dystonia rating scales: critique and recommendations. Mov. Disord. 28, 874–883.10.1002/mds.25579Search in Google Scholar PubMed PubMed Central

Arnold, M. (2018). Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders. Cephalalgia 38, 1–211.10.1177/0333102417738202Search in Google Scholar PubMed

Avenali, M., De Icco, R., Tinazzi, M., Defazio, G., Tronconi, L., and Sandrini, G. (2018). Pain in focal dystonias – a focused review to address an important component of the disease. Parkinsonism Relat. Disord. 54, 17–24.10.1016/j.parkreldis.2018.04.030Search in Google Scholar PubMed

Barbanti, P., Fabbrini, G., Pauletti, C., Defazio, G., Cruccu, G., and Berardelli, A. (2005). Headache in cranial and cervical dystonia. Neurology 64, 1308–1309.10.1212/01.WNL.0000156909.13677.FFSearch in Google Scholar PubMed

Bentivoglio, A.R., Di Stasio, E., Mulas, D., Cerbarano, M.L., Ialongo, T., Laurienzo, A., and Petracca, M. (2017). Long-term abobotulinumtoxin A treatment of cervical dystonia. Neurotox. Res. 32, 291–300.10.1007/s12640-017-9737-6Search in Google Scholar PubMed

Bezerra, M.E. and Rocha-Filho, P.A. (2017). Headache attributed to craniocervical dystonia – a little known headache. Headache 57, 336–343.10.1111/head.12996Search in Google Scholar PubMed

Brashear, A., Lew, M.F., Dykstra, D.D., Comella, C.L., Factor, S.A., and Rodnitzky, R.L. (1999). Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-responsive cervical dystonia. Neurology 53, 1439–1446.10.1212/WNL.53.7.1439Search in Google Scholar PubMed

Camargo, C.H., Cattai, L., and Teive, H.A. (2015). Pain relief in cervical dystonia with botulinum toxin treatment. Toxins (Basel) 7, 2321–2335.10.3390/toxins7062321Search in Google Scholar PubMed PubMed Central

Cano, S.J., Warner, T.T., Linacre, J.M., Bhatia, K.P., Thompson, A.J., Fitzpatrick, R., and Hobart, J.C. (2004). Capturing the true burden of dystonia on patients: the Cervical Dystonia Impact Profile (CDIP-58). Neurology 63, 1629–1633.10.1212/01.WNL.0000142962.11881.26Search in Google Scholar PubMed

Castelao, M., Marques, R.E., Duarte, G.S., Rodrigues, F.B., Ferreira, J., Sampaio, C., Moore, A.P., and Costa, J. (2017). Botulinum toxin type A therapy for cervical dystonia. Cochrane Database Syst. Rev. 12, 1–91.10.1002/14651858.CD003633.pub3Search in Google Scholar PubMed PubMed Central

Charles, D., Brashear, A., Hauser, R.A., Li, H.I., Boo, L.M., and Brin, M.F. (2012). Efficacy, tolerability, and immunogenicity of onabotulinumtoxina in a randomized, double-blind, placebo-controlled trial for cervical dystonia. Clin. Neuropharmacol. 35, 208–214.10.1097/WNF.0b013e31826538c7Search in Google Scholar PubMed

Charles, P.D., Adler, C.H., Stacy, M., Comella, C., Jankovic, J., Adams, A.M, Schwartz, M., and Brin, M.F. (2014). Cervical dystonia and pain: characteristics and treatment patterns from CD PROBE (Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy). J. Neurol. 261, 1309–1319.10.1007/s00415-014-7343-6Search in Google Scholar PubMed PubMed Central

Charles, P.D., Manack Adams, A., Davis, T., Bradley, K., Schwartz, M., Brin, M.F., and Patel, A.T. (2016). Neck pain and cervical dystonia: treatment outcomes from CD PROBE (Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy). Pain Pract. 16, 1073–1082.10.1111/papr.12408Search in Google Scholar PubMed

Comella, C.L., Jankovic, J., Shannon, K.M., Tsui, J., Swenson, M., Leurgans, S., and Fan, W. (2005). Comparison of botulinum toxin serotypes A and B for the treatment of cervical dystonia. Neurology 65, 1423–1429.10.1212/01.wnl.0000183055.81056.5cSearch in Google Scholar PubMed

Comella, C.L., Jankovic, J., Truong, D.D., Hanschmann, A., and Grafe, S. (2011). Efficacy and safety of incobotulinumtoxinA (NT 201, XEOMIN®, botulinum neurotoxin type A, without accessory proteins) in patients with cervical dystonia. J. Neurol. Sci. 308, 103–109.10.1016/j.jns.2011.05.041Search in Google Scholar PubMed

Comella, C.L., Fox, S.H., Bhatia, K.P., Perlmutter, J.S., Jinnah, H.A., Zurowski, M., McDonald, W.M., Marsh, L., Rosen, A.R., Waliczek, T., et al. (2015). Development of the comprehensive cervical dystonia rating scale: methodology. Mov. Disord. Clin. Pract. 2, 135–141.10.1002/mdc3.12131Search in Google Scholar PubMed PubMed Central

Conte, A., McGovern, E.M., Narasimham, S., Beck, R., Killian, O., O’Riordan, S., Reilly, R.B., and Hutchinson, M. (2017a). Temporal discrimination: mechanisms and relevance to adult-onset dystonia. Front. Neurol. 8, 625.10.3389/fneur.2017.00625Search in Google Scholar PubMed PubMed Central

Conte, A., Ferrazzano, G., Belvisi, D., Manzo, N., Suppa, A., Fabbrini, G., and Berardelli, A. (2017b). Does the somatosensory temporal discrimination threshold change over time in focal dystonia? Neural. Plast. 2017, 9848070.10.1155/2017/9848070Search in Google Scholar PubMed PubMed Central

Czekóová, K., Zemánková, P., Shaw, D.J., and Bareš, M. (2017). Social cognition and idiopathic isolated cervical dystonia. J. Neural. Transm. (Vienna) 124, 1097–1104.10.1007/s00702-017-1725-8Search in Google Scholar PubMed

Defazio, G., Jankovic, J., Giel, J.L., and Papapetropoulos, S. (2013). Descriptive epidemiology of cervical dystonia. Tremor Other Hyperkinet. Mov. 3, 193.10.5334/tohm.170Search in Google Scholar

Defazio, G., Esposito, M., Abbruzzese, G., Scaglione, C.L., Fabbrini, G., Ferrazzano, G., Peluso, S., Pellicciari, R., Gigante, A.F, Cossu, G., et al. (2017). The Italian Dystonia Registry: rationale, design and preliminary findings. Neurol. Sci. 38, 819–825.10.1007/s10072-017-2839-3Search in Google Scholar PubMed

Defazio, G., Albanese, A., Pellicciari, R., Scaglione, C.L., Esposito, M., Morgante, F., Abbruzzese, G., Bentivoglio, A.R., Bono, F., Moja, M.C., et al. (2019). Expert recommendations for diagnosing cervical, oromandibular, and limb dystonia. Neurol. Sci. 40, 89–95.10.1007/s10072-018-3586-9Search in Google Scholar PubMed

Dressler, D., Paus, S., Seitzinger, A., Gebhardt, B., and Kupsch, A. (2013). Long-term efficacy and safety of incobotulinumtoxinA injections in patients with cervical dystonia. J. Neurol. Neurosurg. Psychiatry 84, 1014–1019.10.1136/jnnp-2012-303608Search in Google Scholar PubMed PubMed Central

Drinovac, V.V., Bach-Rojecky, L., and Lacković, Z. (2016). Antinociceptive action of botulinum toxin type A in carrageenan-induced mirror pain. J. Neural. Transm. (Vienna) 123, 1403–1413.10.1007/s00702-016-1605-7Search in Google Scholar PubMed

Drinovac, V.V., Filipović, B., Bach-Rojecky, L., and Lacković, Z. (2018). Role of central versus peripheral opioid system in antinociceptive and anti-inflammatory effect of botulinum toxin type A in trigeminal region. Eur. J. Pain. 22, 583–591.10.1002/ejp.1146Search in Google Scholar PubMed

Fan, C., Chu, X., Wang, L., Shi, H., and Li, T. (2017). Botulinum toxin type A reduces TRPV1 expression in the dorsal root ganglion in rats with adjuvant-arthritis pain. Toxicon 133, 116–122.10.1016/j.toxicon.2017.05.001Search in Google Scholar PubMed

Fernandez, H.H., Pappert, E.J., Comella, C.L., Evidente, V.G., Truong, D.D., Verma, A., and Jankovic, J. (2013). Efficacy and safety of incobotulinumtoxin A in subjects previously treated with botulinum toxin versus toxin-naïve subjects with cervical dystonia. Tremor Other Hyperkinet. Mov. 3, 140.Search in Google Scholar

Foley, J.A., Vinke, R.S., Limousin, P., and Cipolotti, L. (2017). Relationship of cognitive function to motor symptoms and mood disorders in patients with isolated dystonia. Cogn. Behav. Neurol. 30, 16–22.10.1097/WNN.0000000000000117Search in Google Scholar PubMed

Hallett, M. (2018). Mechanism of action of botulinum neurotoxin: unexpected consequences. Toxicon 147, 73–76.10.1016/j.toxicon.2017.08.011Search in Google Scholar PubMed PubMed Central

Hawker, G.A., Mian, S., Kendzerska, T., and French, M. (2011). Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res. 11, 240–252.10.1002/acr.20543Search in Google Scholar PubMed

Jost, W.H., Hefter, H., Stenner, A., and Reichel, G. (2013). Rating scales for cervical dystonia: a critical evaluation of tools for outcome assessment of botulinum toxin therapy. J. Neural. Transm. (Vienna) 120, 487–496.10.1007/s00702-012-0887-7Search in Google Scholar PubMed PubMed Central

Kaji, R., Shimizu, H., Takase, T., Osawa, M., and Yanagisawa, N. (2013). A double-blind comparative study to evaluate the efficacy and safety of NerBloc® (rimabotulinumtoxinB) administered in a single dose to patients with cervical dystonia. Brain Nerve 65, 203–211.Search in Google Scholar

Kuyper, D.J., Parra, V., Aerts, S., Okun, M.S., and Kluger, B.M. (2011). Nonmotor manifestations of dystonia: a systematic review. Mov. Disord. 26, 1206–1217.10.1002/mds.23709Search in Google Scholar PubMed PubMed Central

Lew, M.F., Adornato, B.T., Duane, D.D., Dykstra, D.D., Factor, S.A., Massey, J.M., Brin, M.F., Jankovic, J., Rodnitzky, R.L., Singer, C., et al. (1997). Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Neurology 49, 701–707.10.1212/WNL.49.3.701Search in Google Scholar PubMed

Marino, M.J., Terashima, T., Steinauer, J.J., Eddinger, K.A., Yaksh, T.L., and Xu, Q. (2014). Botulinum toxin B in the sensory afferent: transmitter release, spinal activation, and pain behavior. Pain 155, 674–684.10.1016/j.pain.2013.12.009Search in Google Scholar PubMed PubMed Central

Misra, V.P., Trosch, R.M., Maisonobe, P., and Om, S. (2018). Spectrum of practice in the routine management of cervical dystonia with abobotulinumtoxinA: findings from three prospective open-label observational studies. J. Clin. Mov. Disord. 5, 4.10.1186/s40734-018-0072-8Search in Google Scholar PubMed PubMed Central

Morgante, F., Matinella, A., Andrenelli, E., Ricciardi, L., Allegra, C., and Terranova, C. (2018). Pain processing in functional and idiopathic dystonia: an exploratory study. Mov Disord. 33, 1340–1348.10.1002/mds.27402Search in Google Scholar PubMed

Novak, I., Campbell, L., Boyce, M., and Fung, V.S. (2010). Botulinum toxin assessment, intervention and aftercare for cervical dystonia and other causes of hypertonia of the neck: international consensus statement. Eur. J. Neurol. 17, 94–108.10.1111/j.1468-1331.2010.03130.xSearch in Google Scholar PubMed

Paracka, L., Wegner, F., Blahak, C., Abdallat, M., Saryyeva, A., Dressler, D., Karst, M., and Krauss, J.K. (2017). Sensory alterations in patients with isolated idiopathic dystonia: an exploratory quantitative sensory testing analysis. Front. Neurol. 8, 553.10.3389/fneur.2017.00553Search in Google Scholar PubMed PubMed Central

Park, J. and Chung, M.E. (2018). Botulinum toxin for central neuropathic pain. Toxins (Basel) 10, 224.10.3390/toxins10060224Search in Google Scholar PubMed PubMed Central

Park, J. and Park, H.J. (2017). Botulinum toxin for the treatment of neuropathic pain. Toxins (Basel). 9, 260.10.3390/toxins9090260Search in Google Scholar PubMed PubMed Central

Poewe, W., Deuschl, G., Nebe, A., Feifel, E., Wissel, J., Benecke, R., Kessler, K.R., Ceballos-Baumann, A.O., Ohly, A., Oertel, W., et al. (1998). What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. J. Neurol. Neurosurg. Psychiatry 64, 13–17.10.1136/jnnp.64.1.13Search in Google Scholar

Ranoux, D., Gury, C., Fondarai, J., Mas, J.L., and Zuber, M. (2002). Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia. J. Neurol. Neurosurg. Psychiatry 72, 459–462.Search in Google Scholar

Reichel, G. (2011). Cervical dystonia: a new phenomenological classification for botulinum toxin therapy. Basal Ganglia 1, 5–12.10.1016/j.baga.2011.01.001Search in Google Scholar

Relja, M. and Miletić, V. (2017). When movement disorders hurt: addressing pain in hyperkinetic disorders. Parkinsonism Relat. Disord. 44, 110–113.10.1016/j.parkreldis.2017.08.011Search in Google Scholar

Safarpour, Y. and Jabbari, B. (2018). Botulinum toxin treatment of movement disorders. Curr. Treat. Options Neurol. 20, 4.10.1007/s11940-018-0488-3Search in Google Scholar

Scontrini, A., Conte, A., Defazio, G., Fiorio, M., Fabbrini, G., Suppa, A., Tinazzi, M., and Berardelli, A. (2009). Somatosensory temporal discrimination in patients with primary focal dystonia. J. Neurol. Neurosurg. Psychiatry 80, 1315–1319.10.1136/jnnp.2009.178236Search in Google Scholar

Shin, M.C., Wakita, M., Xie, D.J., Yamaga, T., Iwata, S., Torii, Y., Harakawa, T., Ginnaga, A., Kozaki, S., and Akaike, N. (2012). Inhibition of membrane Na+ channels by A type botulinum toxin at femtomolar concentrations in central and peripheral neurons. J. Pharmacol. Sci. 118, 33–42.10.1254/jphs.11060FPSearch in Google Scholar

Shrestha, M. and Chen, A. (2018). Modalities in managing postherpetic neuralgia. Korean J. Pain 31, 235–243.10.3344/kjp.2018.31.4.235Search in Google Scholar

Simpson, D.M., Hallett, M., Ashman, E.J., Comella, C.L., Green, M.W., Gronseth, G.S., Armstrong, M.J., Gloss, D., Potrebic, S., Jankovic, J., et al. (2016). Practice guideline update summary: botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache. Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 86, 1818–1826.10.1212/WNL.0000000000002560Search in Google Scholar

Smit, M., Kuiper, A., Han, V., Jiawan, V.C.R., Douma, G., van Harten, B., Oen, J.M.T.H., Pouwels, M.E., Dieks, H.J.G., Bartels, A.L., et al. (2016). Psychiatric co-morbidity is highly prevalent in idiopathic cervical dystonia and significantly influences health-related quality of life: results of a controlled study. Parkinsonism Relat. Disord. 30, 7–12.10.1016/j.parkreldis.2016.06.004Search in Google Scholar

Stacy, M. (2008). Epidemiology, clinical presentation, and diagnosis of cervical dystonia. Neurol. Clin. 26, 23–42.10.1016/S0733-8619(08)80003-5Search in Google Scholar

Tater, P. and Pandey, S. (2018). Botulinum toxin in movement disorders. Neurol. India 66, 79–89.10.4103/0028-3886.226441Search in Google Scholar PubMed

Tinazzi, M., Valeriani, M., Squintani, G., Corrà, F., Recchia, S., Defazio, G., and Berardelli, A. (2012). Nociceptive pathway function is normal in cervical dystonia: a study using laser-evoked potentials. J. Neurol. 259, 2060–2066.10.1007/s00415-012-6454-1Search in Google Scholar PubMed

Torres, J.A.K.L. and Rosales, R.L. (2017). Nonmotor symptoms in dystonia. Int Rev Neurobiol. 134, 1335–1371.10.1016/bs.irn.2017.05.003Search in Google Scholar PubMed

Trosch, R., Misra, P., Maisonobe, P., and Om, S. (2016). Geographic differences in pain perception in patients with cervical dystonia. Neurology 86, 33.Search in Google Scholar

Williams, L., McGovern, E., Kimmich, O., Molloy, A., Beiser, I., Butler, J.S., Molloy, F., Logan, P., Healy, D.G., Lynch, T., et al. (2017). Epidemiological, clinical and genetic aspects of adult onset isolated focal dystonia in Ireland. Eur. J. Neurol. 24, 73–81.10.1111/ene.13133Search in Google Scholar PubMed

Yun, J.Y., Kim, J.W., Kim, H.T., Chung, S.J., Kim, J.M., Cho, J.W., Lee, J.Y., Lee, H.N., You, S., Oh, E., et al. (2015). Dysport and Botox at a ratio of 2.5:1 units in cervical dystonia: a double-blind, randomized study. Mov. Disord. 30, 206–213.10.1002/mds.26085Search in Google Scholar PubMed PubMed Central

Zhang, Y. and Smith, C.P. (2015). Botulinum toxin to treat pelvic pain. Toxicon 147, 129–133.10.1016/j.toxicon.2017.08.017Search in Google Scholar PubMed

Received: 2018-12-29
Accepted: 2019-01-25
Published Online: 2019-03-27
Published in Print: 2019-10-25

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