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Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an experimental study

Year 2015, Volume: 49 Issue: 4, 447 - 452, 19.08.2015

Abstract

Objective: Rotator cuff repair is associated with multiple complications, significant morbidity, and re-intervention, which could be mitigated by postoperative chemodeneveration with botulinum toxin-A (BTX-A). This study evaluated the antinociceptive and paralytic effects of BTX-A on an experimental supraspinatus repair rat model and its effect on functional outcomes (running performance).
Methods: Thirty rats were grouped into the surgical repair group (group A), repair + intramuscular BTX-A group (group B), or control group (group C). At the end of the 3-month follow-up, running performance of the rats on a motorized treadmill was evaluated in four time periods (0–30 min, 30–60 min, 60–90 min, and 90–110 min), and penalty points (i.e., number of shock stimuli per lane) were recorded. Afterwards, the supraspinatus muscles were removed and evaluated histologically.
Results: Regarding running performance, group B received significantly fewer penalty points than did group A (p<0.05). The penalty points received were not significantly different between groups B and C in the first three time periods, but were significantly higher in group B at the 90–110-min interval than in group C. On necropsy, all repaired tendons were intact, with no sign of failure at the repair site. Histological evaluation revealed marked degeneration and necrosis of muscles in both repair groups, which was much less evident in group B. Groups A and B had less fatty infiltration than group C.
Conclusion: BTX-A injections resulted in a better function based on running performance, probably due to decreased tissue tension at the repair site and less pain. Further studies on humans are needed to demonstrate this effect clinically.

 

DOI: 10.3944/AOTT.2015.14.0296


References

  • Kim KC, Shin HD, Lee WY, Han SC. Repair integrity and functional outcome after arthroscopic rotator cuff repair: double-row versus suture-bridge technique. Am J Sports Med 2012;40:294–9.
  • Accousti KJ, Flatow EL. Technical pearls on how to maximize healing of the rotator cuff. Instr Course Lect 2007;56:3–12.
  • Palmes D, Spiegel HU, Schneider TO, Langer M, Strat- mann U, Budny T, et al. Achilles tendon healing: long- term biomechanical effects of postoperative mobilization and immobilization in a new mouse model. J Orthop Res 2002;20:939–46.
  • Choueka J, Heminger H, Mass DP. Cyclical testing of zone II flexor tendon repairs. J Hand Surg Am 2000;25:1127– 34.
  • Chan K, MacDermid JC, Hoppe DJ, Ayeni OR, Bhandari M, Foote CJ, et al. Delayed versus early motion after ar- throscopic rotator cuff repair: a meta-analysis. J Shoulder Elbow Surg 2014;23:1631–9.
  • Chang KV, Hung CY, Han DS, Chen WS, Wang TG, Chien KL. Early Versus Delayed Passive Range of Motion Exercise for Arthroscopic Rotator Cuff Repair: A Meta- analysis of Randomized Controlled Trials. Am J Sports Med 2015;43:1265–73.
  • Dressler D, Adib Saberi F. Botulinum toxin: mechanisms of action. Eur Neurol 2005;53:3–9.
  • Chen CM, Stott NS, Smith HK. Effects of botulinum toxin A injection and exercise on the growth of juve- nile rat gastrocnemius muscle. J Appl Physiol (1985) 2002;93:1437–47.
  • Truong DD, Jost WH. Botulinum toxin: clinical use. Par- kinsonism Relat Disord 2006;12:331–55.
  • Mahowald ML, Krug HE, Singh JA, Dykstra D. Intra-ar- ticular Botulinum Toxin Type A: a new approach to treat arthritis joint pain. Toxicon 2009;54:658–67.
  • Ma J, Shen J, Smith BP, Ritting A, Smith TL, Koman LA. Bioprotection of tendon repair: adjunctive use of botuli- num toxin A in Achilles tendon repair in the rat. J Bone Joint Surg Am 2007;89:2241–9.
  • Tuzuner S, Özkan Ö, Erin N, Özkaynak S, Cinpolat A, Özkan Ö. Effects of botulinum toxin A injection on heal- ing and tensile strength of ruptured rabbit Achilles ten- dons. Ann Plast Surg 2015;74:496–500.
  • Tekin D, Dursun AD, Fıçıcılar H. The body weight-per- formance relationship of rats on treadmill running. JEPon- line 2008;11;6,44–55.
  • van der Meijden OA, Westgard P, Chandler Z, Gaskill TR, Kokmeyer D, Millett PJ. Rehabilitation after arthroscopic rotator cuff repair: current concepts review and evidence- based guidelines. Int J Sports Phys Ther 2012;7:197–218.
  • Kubat WD, Rekant M. Botulinum toxin use as an adjunc- tive modality in a patient with multiple flexor tendon rup- tures. Hand (N Y) 2008;3:237–9.
  • Ishikawa H, Mitsui Y, Yoshitomi T, Mashimo K, Aoki S, Mukuno K, et al. Presynaptic effects of botulinum toxin type A on the neuronally evoked response of albino and pigmented rabbit iris sphincter and dilator muscles. Jpn J Ophthalmol 2000;44:106–9.
  • Mahowald ML, Singh JA, Dykstra D. Long term effects of intra-articular botulinum toxin A for refractory joint pain. Neurotox Res 2006;9:179–88.
  • Galatz LM, Charlton N, Das R, Kim HM, Havlioglu N, Thomopoulos S. Complete removal of load is detri- mental to rotator cuff healing. J Shoulder Elbow Surg 2009;18:669–75.
  • Gimbel JA, Van Kleunen JP, Lake SP, Williams GR, So- slowsky LJ. The role of repair tension on tendon to bone healing in an animal model of chronic rotator cuff tears. J Biomech 2007;40:561–8.
  • Hettrich CM, Rodeo SA, Hannafin JA, Ehteshami J, Shu- bin Stein BE. The effect of muscle paralysis using Botox on the healing of tendon to bone in a rat model. J Shoulder Elbow Surg 2011;20:688–97.
  • Legerlotz K, Matthews KG, McMahon CD, Smith HK. Botulinum toxin-induced paralysis leads to slower myosin heavy chain isoform composition and reduced titin con- tent in juvenile rat gastrocnemius muscle. Muscle Nerve 2009;39:472–9.
  • Ma J, Elsaidi GA, Smith TL, Walker FO, Tan KH, Martin E, et al. Time course of recovery of juvenile skeletal muscle after botulinum toxin A injection: an animal model study. Am J Phys Med Rehabil 2004;83:774–83.
  • Eliasson P, Andersson T, Aspenberg P. Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase. J Orthop Res 2012;30:274–9.

İntramüsküler botulinum toksin-a’nın etkisi: sıçan rotator manşet tamir modelinde deneysel bir çalışma

Year 2015, Volume: 49 Issue: 4, 447 - 452, 19.08.2015

Abstract

Giriş: Bu çalışmada, deneysel olarak oluşturulan supraspinatus tamir modelinde Botulinum toxin- A (BTX-A)’ nın antinosiseptif (ağrı azaltıcı) ve paralitik özellikleri değerlendirildi ve sıçanların koşu performansına olan etkisi araştırıldı.

Metodlar: 30 adet sıçan, tamir grubu (Grup A), tamir + intramüsküler BTX-A grubu (grup B) ve kontrol grubu (grup C) olarak üç adet sınıfa ayrıldı. Üç aylık takip sonrasında, sıçanların motorlu koşu bandı üzerinde koşu performansı dört zaman dilimli egzersiz protokolü uygulanarak (0-30 dk., 30-60 dk., 60-90 dk., 90-110 dk.) değerlendirildi ve ceza puanları kaydedildi. Sonrasında supraspinatus kasları ayrılarak histolojik açıdan incelendi.

Sonuçlar: Koşu performansına göre değerlendirildiğinde, B grubu, A grubuna göre anlamlı şekilde daha az ceza puanı aldı (p<0, 05). İlk üç zaman dilimine bakıldığında B grubu ve C grubu arasında ceza puanı açısından anlamlı bir fark bulunmadı. 90-110 dk zaman dilimine bakıldığında B grubu sıçanlar C grubuna göre daha fazla ceza puanı aldılar ve anlamlı bir fark olduğu görüldü. Nekropsi sırasında tamir edilen tüm tendonların sağlam olduğu görüldü ve tamir alanında bozulma izlenmedi. Histolojik değerlendirmede B grubunda daha az olmakla beraber her iki tamir grubunda da kasların dejenere ve nekroze olduğu görüldü. A ve B grubunda yağ infiltrasyonu daha azdı.

Çıkarımlar: Botulinum toxin- A (BTX-A)’ nın antinosiseptif (ağrı azaltıcı) ve paralitik etkisi koşu performansının daha iyi olmasına sebep olmuştur. Bu durum tamir alanında doku gerginliğinin ve ağrının daha az olması ile ilişkilendirilebilir. Klinikte etkisini görmek için birçok insan çalışmasına ihtiyaç vardır.

Anahtar kelimeler: Botulinum toxin A (BTX-A), rotator manşet yaralanması, omuz rehabilitasyonu, hayvan çalışması.

 

DOI: 10.3944/AOTT.2015.14.0296

Bu özet, makalenin henüz redaksiyonu tamamlanmamış haline aittir ve bilgi verme amaçlıdır. Yayın aşamasında değişiklik gösterebilir.

References

  • Kim KC, Shin HD, Lee WY, Han SC. Repair integrity and functional outcome after arthroscopic rotator cuff repair: double-row versus suture-bridge technique. Am J Sports Med 2012;40:294–9.
  • Accousti KJ, Flatow EL. Technical pearls on how to maximize healing of the rotator cuff. Instr Course Lect 2007;56:3–12.
  • Palmes D, Spiegel HU, Schneider TO, Langer M, Strat- mann U, Budny T, et al. Achilles tendon healing: long- term biomechanical effects of postoperative mobilization and immobilization in a new mouse model. J Orthop Res 2002;20:939–46.
  • Choueka J, Heminger H, Mass DP. Cyclical testing of zone II flexor tendon repairs. J Hand Surg Am 2000;25:1127– 34.
  • Chan K, MacDermid JC, Hoppe DJ, Ayeni OR, Bhandari M, Foote CJ, et al. Delayed versus early motion after ar- throscopic rotator cuff repair: a meta-analysis. J Shoulder Elbow Surg 2014;23:1631–9.
  • Chang KV, Hung CY, Han DS, Chen WS, Wang TG, Chien KL. Early Versus Delayed Passive Range of Motion Exercise for Arthroscopic Rotator Cuff Repair: A Meta- analysis of Randomized Controlled Trials. Am J Sports Med 2015;43:1265–73.
  • Dressler D, Adib Saberi F. Botulinum toxin: mechanisms of action. Eur Neurol 2005;53:3–9.
  • Chen CM, Stott NS, Smith HK. Effects of botulinum toxin A injection and exercise on the growth of juve- nile rat gastrocnemius muscle. J Appl Physiol (1985) 2002;93:1437–47.
  • Truong DD, Jost WH. Botulinum toxin: clinical use. Par- kinsonism Relat Disord 2006;12:331–55.
  • Mahowald ML, Krug HE, Singh JA, Dykstra D. Intra-ar- ticular Botulinum Toxin Type A: a new approach to treat arthritis joint pain. Toxicon 2009;54:658–67.
  • Ma J, Shen J, Smith BP, Ritting A, Smith TL, Koman LA. Bioprotection of tendon repair: adjunctive use of botuli- num toxin A in Achilles tendon repair in the rat. J Bone Joint Surg Am 2007;89:2241–9.
  • Tuzuner S, Özkan Ö, Erin N, Özkaynak S, Cinpolat A, Özkan Ö. Effects of botulinum toxin A injection on heal- ing and tensile strength of ruptured rabbit Achilles ten- dons. Ann Plast Surg 2015;74:496–500.
  • Tekin D, Dursun AD, Fıçıcılar H. The body weight-per- formance relationship of rats on treadmill running. JEPon- line 2008;11;6,44–55.
  • van der Meijden OA, Westgard P, Chandler Z, Gaskill TR, Kokmeyer D, Millett PJ. Rehabilitation after arthroscopic rotator cuff repair: current concepts review and evidence- based guidelines. Int J Sports Phys Ther 2012;7:197–218.
  • Kubat WD, Rekant M. Botulinum toxin use as an adjunc- tive modality in a patient with multiple flexor tendon rup- tures. Hand (N Y) 2008;3:237–9.
  • Ishikawa H, Mitsui Y, Yoshitomi T, Mashimo K, Aoki S, Mukuno K, et al. Presynaptic effects of botulinum toxin type A on the neuronally evoked response of albino and pigmented rabbit iris sphincter and dilator muscles. Jpn J Ophthalmol 2000;44:106–9.
  • Mahowald ML, Singh JA, Dykstra D. Long term effects of intra-articular botulinum toxin A for refractory joint pain. Neurotox Res 2006;9:179–88.
  • Galatz LM, Charlton N, Das R, Kim HM, Havlioglu N, Thomopoulos S. Complete removal of load is detri- mental to rotator cuff healing. J Shoulder Elbow Surg 2009;18:669–75.
  • Gimbel JA, Van Kleunen JP, Lake SP, Williams GR, So- slowsky LJ. The role of repair tension on tendon to bone healing in an animal model of chronic rotator cuff tears. J Biomech 2007;40:561–8.
  • Hettrich CM, Rodeo SA, Hannafin JA, Ehteshami J, Shu- bin Stein BE. The effect of muscle paralysis using Botox on the healing of tendon to bone in a rat model. J Shoulder Elbow Surg 2011;20:688–97.
  • Legerlotz K, Matthews KG, McMahon CD, Smith HK. Botulinum toxin-induced paralysis leads to slower myosin heavy chain isoform composition and reduced titin con- tent in juvenile rat gastrocnemius muscle. Muscle Nerve 2009;39:472–9.
  • Ma J, Elsaidi GA, Smith TL, Walker FO, Tan KH, Martin E, et al. Time course of recovery of juvenile skeletal muscle after botulinum toxin A injection: an animal model study. Am J Phys Med Rehabil 2004;83:774–83.
  • Eliasson P, Andersson T, Aspenberg P. Achilles tendon healing in rats is improved by intermittent mechanical loading during the inflammatory phase. J Orthop Res 2012;30:274–9.
There are 23 citations in total.

Details

Primary Language English
Journal Section Experimental Study
Authors

Ercan Sahin

Mahmut Kalem

Sinan Zehir

Murat Songur

Mehmet Demirtas This is me

Publication Date August 19, 2015
Published in Issue Year 2015 Volume: 49 Issue: 4

Cite

APA Sahin, E., Kalem, M., Zehir, S., Songur, M., et al. (2015). Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an experimental study. Acta Orthopaedica Et Traumatologica Turcica, 49(4), 447-452. https://doi.org/10.3944/AOTT.2015.14.0296
AMA Sahin E, Kalem M, Zehir S, Songur M, Demirtas M. Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an experimental study. Acta Orthopaedica et Traumatologica Turcica. August 2015;49(4):447-452. doi:10.3944/AOTT.2015.14.0296
Chicago Sahin, Ercan, Mahmut Kalem, Sinan Zehir, Murat Songur, and Mehmet Demirtas. “Effect of Intramuscular Botulinum Toxin-A in a Rat Rotator Cuff Repair Model: An Experimental Study”. Acta Orthopaedica Et Traumatologica Turcica 49, no. 4 (August 2015): 447-52. https://doi.org/10.3944/AOTT.2015.14.0296.
EndNote Sahin E, Kalem M, Zehir S, Songur M, Demirtas M (August 1, 2015) Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an experimental study. Acta Orthopaedica et Traumatologica Turcica 49 4 447–452.
IEEE E. Sahin, M. Kalem, S. Zehir, M. Songur, and M. Demirtas, “Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an experimental study”, Acta Orthopaedica et Traumatologica Turcica, vol. 49, no. 4, pp. 447–452, 2015, doi: 10.3944/AOTT.2015.14.0296.
ISNAD Sahin, Ercan et al. “Effect of Intramuscular Botulinum Toxin-A in a Rat Rotator Cuff Repair Model: An Experimental Study”. Acta Orthopaedica et Traumatologica Turcica 49/4 (August 2015), 447-452. https://doi.org/10.3944/AOTT.2015.14.0296.
JAMA Sahin E, Kalem M, Zehir S, Songur M, Demirtas M. Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an experimental study. Acta Orthopaedica et Traumatologica Turcica. 2015;49:447–452.
MLA Sahin, Ercan et al. “Effect of Intramuscular Botulinum Toxin-A in a Rat Rotator Cuff Repair Model: An Experimental Study”. Acta Orthopaedica Et Traumatologica Turcica, vol. 49, no. 4, 2015, pp. 447-52, doi:10.3944/AOTT.2015.14.0296.
Vancouver Sahin E, Kalem M, Zehir S, Songur M, Demirtas M. Effect of intramuscular botulinum toxin-A in a rat rotator cuff repair model: an experimental study. Acta Orthopaedica et Traumatologica Turcica. 2015;49(4):447-52.