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Experimental Brain Research

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01.04.2016 | Research Article

Corticomotor control of lumbar multifidus muscles is impaired in chronic low back pain: concurrent evidence from ultrasound imaging and double-pulse transcranial magnetic stimulation

verfasst von: Hugo Massé-Alarie, Louis-David Beaulieu, Richard Preuss, Cyril Schneider

Erschienen in: Experimental Brain Research | Ausgabe 4/2016

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Abstract

Chronic low back pain (CLBP) is often associated with impaired control of deep trunk muscles and reorganization of the primary motor areas (M1). Precisely, functional changes of the lumbar multifidus muscles (MF) involved in spine stability may be of special interest in rehabilitation. Therefore, we tested MF corticomotor control using double transcranial magnetic stimulation (TMS) paradigms for the first time in this muscle and examined its link with MF volitional activation. Eleven individuals with lateralized CLBP and 13 pain-free participants were recruited. Ultrasound imaging enabled measurement of MF volitional isometric contraction in prone lying. TMS of MF M1 area was used to test hemispheric excitability and mechanisms in relation to motor programming, i.e., active motor threshold (AMT), amplitude of motor-evoked potentials and short-interval intracortical inhibition (SICI) and facilitation (SICF). In CLBP, SICI level was lower in the left hemisphere and MF volitional contraction was not related to AMT (M1 excitability), conversely to what was observed in the pain-free group. No other between-group difference was detected. These original findings support a plasticity of cortical maps controlling paravertebral muscles and likely including a different motor strategy for the control of MF. Changes of M1 function may thus underlie impaired motor control of lumbopelvic spine and pain persistence in CLBP.

Apkarian AV, Hashmi JA, Baliki MN (2011) Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152:S49–S64. doi:10.1016/j.pain.2010.11.010 CrossRefPubMedPubMedCentral

Bachtiar V, Stagg CJ (2014) The role of inhibition in human motor cortical plasticity. Neuroscience 278:93–104. doi:10.1016/j.neuroscience.2014.07.059 CrossRefPubMed

Baliki MN, Petre B, Torbey S et al. (2012) Corticostriatal functional connectivity predicts transition to chronic back pain. Nat Neurosci 15:1117–1119. doi:10.1038/nn.3153 CrossRefPubMedPubMedCentral

Butefisch C, Davis B, Wise S, Sawaki L, Kopylev L, Classen J, Cohen L (2000) Mechanisms of use-dependent plasticity in the human motor cortex. Proc Natl Acad Sci USA 97:3661–3665CrossRefPubMedPubMedCentral

Byblow WD, Stinear CM (2006) Modulation of short-latency intracortical inhibition in human primary motor cortex during synchronised versus syncopated finger movements. Exp Brain Res 168:287–293. doi:10.1007/s00221-005-0205-9 CrossRefPubMed

Carr LJ, Harrison LM, Stephens JA (1994) Evidence for bilateral innervation of certain homologous motoneurone pools in man. J Physiol 475:217–227CrossRefPubMedPubMedCentral

Chen R, Tam A, Butefisch C, Corwell B, Ziemann U, Rothwell JC, Cohen LG (1998) Intracortical inhibition and facilitation in different representations of the human motor cortex. J Neurophysiol 80:2870–2881PubMed

Claus AP, Hides JA, Moseley GL, Hodges PW (2009a) Different ways to balance the spine: subtle changes in sagittal spinal curves affect regional muscle activity. Spine (Phila Pa 1976) 34:E208–E214. doi:10.1097/BRS.0b013e3181908ead00007632-200903150-00021 CrossRef

Claus AP, Hides JA, Moseley GL, Hodges PW (2009b) Is ‘ideal’ sitting posture real? Measurement of spinal curves in four sitting postures. Man Ther 14:404–408. doi:10.1016/j.math.2008.06.001 CrossRefPubMed

Coghill RC, Gilron I, Iadarola MJ (2001) Hemispheric lateralization of somatosensory processing. J Neurophysiol 85:2602–2612PubMed

Dankaerts W, O’Sullivan P, Burnett A, Straker L (2006) Altered patterns of superficial trunk muscle activation during sitting in nonspecific chronic low back pain patients: importance of subclassification. Spine (Phila Pa 1976) 31:2017–2023. doi:10.1097/01.brs.0000228728.11076.8200007632-200608010-00021 CrossRef

Davey NJ, Lisle RM, Loxton-Edwards B, Nowicky AV, McGregor AH (2002) Activation of back muscles during voluntary abduction of the contralateral arm in humans. Spine (Phila Pa 1976) 27:1355–1360CrossRef

D’Hooge R, Cagnie B, Crombez G, Vanderstraeten G, Dolphens M, Danneels L (2012) Increased intramuscular fatty infiltration without differences in lumbar muscle cross-sectional area during remission of unilateral recurrent low back pain. Man Ther 17:584–588. doi:10.1016/j.math.2012.06.007S1356-689X(12)00148-8 CrossRefPubMed

Dum RP, Li C, Strick PL (2002) Motor and nonmotor domains in the monkey dentate. Ann N Y Acad Sci 978:289–301CrossRefPubMed

Ferbert A, Caramia D, Priori A, Bertolasi L, Rothwell JC (1992) Cortical projection to erector spinae muscles in man as assessed by focal transcranial magnetic stimulation. Electroencephal Clin Neurophysiol Evoked Potent Sect 85:382–387CrossRef

Ferreira PH, Ferreira ML, Hodges PW (2004) Changes in recruitment of the abdominal muscles in people with low back pain: ultrasound measurement of muscle activity. Spine (Phila Pa 1976) 29:2560–2566CrossRef

Ferreira PH, Ferreira ML, Maher CG, Refshauge K, Herbert RD, Hodges PW (2010) Changes in recruitment of transversus abdominis correlate with disability in people with chronic low back pain. Br J Sports Med 44:1166–1172. doi:10.1136/bjsm.2009.061515 CrossRefPubMed

Flor H, Braun C, Elbert T, Birbaumer N (1997) Extensive reorganization of primary somatosensory cortex in chronic back pain patients. Neurosci Lett 224:5–8CrossRefPubMed

Gagné M, Schneider C (2008a) Dynamic influence of wrist flexion and extension on the intracortical inhibition of the first dorsal interosseus muscle during precision grip. Brain Res 1195:77–88CrossRefPubMed

Gagné M, Schneider C (2008b) Dynamic influence of wrist flexion and extension on the intracortical inhibition of the first dorsal interosseus muscle during precision grip. Brain Res 1195:77–88. doi:10.1016/j.brainres.2007.12.021 CrossRefPubMed

Hebert JJ, Koppenhaver SL, Parent EC, Fritz JM (2009) A systematic review of the reliability of rehabilitative ultrasound imaging for the quantitative assessment of the abdominal and lumbar trunk muscles. Spine (Phila Pa 1976) 34:E848–E856. doi:10.1097/BRS.0b013e3181ae625c00007632-200911010-00029 CrossRef

Hides J, Stanton W, Mendis MD, Sexton M (2011) The relationship of transversus abdominis and lumbar multifidus clinical muscle tests in patients with chronic low back pain. Man Ther 16:573–577. doi:10.1016/j.math.2011.05.007 CrossRefPubMed

Hodges PW (2012) Functional implications of musculoskeletal pain: Mechanisms and rehabilitation. In: 14th world congress on pain, Milano, Italia

Hodges PW, Richardson CA (1996) Inefficient muscular stabilization of the lumbar spine associated with low back pain. A motor control evaluation of transversus abdominis. Spine (Phila Pa 1976) 21:2640–2650CrossRef

Hodges PW, Tucker K (2011) Moving differently in pain: a new theory to explain the adaptation to pain. Pain 152:S90–S98. doi:10.1016/j.pain.2010.10.020 CrossRefPubMed

Hsieh JC, Hannerz J, Ingvar M (1996) Right-lateralised central processing for pain of nitroglycerin-induced cluster headache. Pain 67:59–68CrossRefPubMed

Jensen R, Hystad T, Kvale A, Baerheim A (2007) Quantitative sensory testing of patients with long lasting Patellofemoral pain syndrome. Eur J Pain 11:665–676. doi:10.1016/j.ejpain.2006.10.007 CrossRefPubMed

Kaneko T, Caria MA, Asanuma H (1994) Information processing within the motor cortex. II. Intracortical connections between neurons receiving somatosensory cortical input and motor output neurons of the cortex. J Comp Neurol 345:172–184. doi:10.1002/cne.903450203 CrossRefPubMed

Keller A (1993) Intrinsic synaptic organization of the motor cortex. Cereb Cortex 3:430–441CrossRefPubMed

Kiesel KB, Uhl TL, Underwood FB, Rodd DW, Nitz AJ (2007a) Measurement of lumbar multifidus muscle contraction with rehabilitative ultrasound imaging. Man Ther 12:161–166. doi:10.1016/j.math.2006.06.011 CrossRefPubMed

Kiesel KB, Underwood FB, Mattacola CG, Nitz AJ, Malone TR (2007b) A comparison of select trunk muscle thickness change between subjects with low back pain classified in the treatment-based classification system and asymptomatic controls. J Orthop Sports Phys Ther 37:596–607CrossRefPubMed

Kjaer P, Bendix T, Sorensen JS, Korsholm L, Leboeuf-Yde C (2007) Are MRI-defined fat infiltrations in the multifidus muscles associated with low back pain? BMC Med 5:2. doi:10.1186/1741-7015-5-2 CrossRefPubMedPubMedCentral

Kosek E, Hansson P (2002) The influence of experimental pain intensity in the local and referred pain area on somatosensory perception in the area of referred pain. Eur J Pain 6:413–425CrossRefPubMed

Kujirai T, Caramia MD, Rothwell JC et al (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519CrossRefPubMedPubMedCentral

Lefaucheur JP, Drouot X, Menard-Lefaucheur I, Keravel Y, Nguyen JP (2006) Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain. Neurology 67:1568–1574. doi:10.1212/01.wnl.0000242731.10074.3c CrossRefPubMed

Lefaucheur JP, Ayache SS, Sorel M et al (2012) Analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex in neuropathic pain: influence of theta burst stimulation priming. Eur J Pain 16:1403–1413. doi:10.1002/j.1532-2149.2012.00150.x CrossRefPubMed

Masse-Alarie H, Flamand VH, Moffet H, Schneider C (2012) Corticomotor control of deep abdominal muscles in chronic low back pain and anticipatory postural adjustments. Exp Brain Res 218:99–109. doi:10.1007/s00221-012-3008-9 CrossRefPubMed

Masse-Alarie H, Flamand VH, Moffet H, Schneider C (2013) Peripheral neurostimulation and specific motor training of deep abdominal muscles improve posturomotor control in chronic low back pain. Clin J Pain 29:814–823. doi:10.1097/AJP.0b013e318276a058 CrossRefPubMed

Masse-Alarie H, Beaulieu LD, Preuss R, Schneider C (2014) Impairment of corticomotor control of lumbar multifidus in chronic low back pain. In: 35th annual scientific meeting of the Canadian pain society, Quebec city

Mhalla A, de Andrade DC, Baudic S, Perrot S, Bouhassira D (2010) Alteration of cortical excitability in patients with fibromyalgia. Pain 149:495–500. doi:10.1016/j.pain.2010.03.009 CrossRefPubMed

Moseley GL, Hodges PW, Gandevia SC (2002) Deep and superficial fibers of the lumbar multifidus muscle are differentially active during voluntary arm movements. Spine (Phila Pa 1976) 27:E29–E36CrossRef

Nathan PW, Smith M, Deacon P (1996) Vestibulospinal, reticulospinal and descending propriospinal nerve fibres in man. Brain 119(Pt 6):1809–1833CrossRefPubMed

Nowicky AV, McGregor AH, Davey NJ (2001) Corticospinal control of human erector spinae muscles. Mot Control 5:270–280

O’Connell NE, Maskill DW, Cossar J, Nowicky AV (2007) Mapping the cortical representation of the lumbar paravertebral muscles. Clin Neurophysiol 118:2451–2455. doi:10.1016/j.clinph.2007.08.006 CrossRefPubMed

Ortu E, Deriu F, Suppa A, Tolu E, Rothwell JC (2008) Effects of volitional contraction on intracortical inhibition and facilitation in the human motor cortex. J Physiol 586:5147–5159CrossRefPubMedPubMedCentral

O’Sullivan PB, Dankaerts W, Burnett AF, Farrell GT, Jefford E, Naylor CS, O’Sullivan KJ (2006) Effect of different upright sitting postures on spinal-pelvic curvature and trunk muscle activation in a pain-free population. Spine (Phila Pa 1976) 31:E707–E712. doi:10.1097/01.brs.0000234735.98075.5000007632-200609010-00024 CrossRef

Peurala SH, Muller-Dahlhaus JF, Arai N (2008) Ziemann U (2008) Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF). Clin Neurophysiol 119:2291–2297. doi:10.1016/j.clinph.05.031S1388-2457(08)00584-1 CrossRefPubMed

Pijnenburg M, Brumagne S, Caeyenberghs K et al. (2015) Resting-state functional connectivity of the sensorimotor network in individuals with nonspecific low back pain and the association with the sit-to- stand-to-sit task. Brain Connect 5:303–311. doi:10.1089/brain.2014.0309 CrossRefPubMed

Reis J, Swayne OB, Vandermeeren Y et al (2008) Contribution of transcranial magnetic stimulation to the understanding of cortical mechanisms involved in motor control. J Physiol 586:325–351. doi:10.1113/jphysiol.2007.144824 CrossRefPubMedPubMedCentral

Reynolds C, Ashby P (1999) Inhibition in the human motor cortex is reduced just before a voluntary contraction. Neurology 53:730–735CrossRefPubMed

Richardson CA, Hides JA, Hodges PW (2004) Therapeutic exercise for lumbopelvic stabilization: a motor control approach for the treatment and prevention of low back pain. Elsevier, Edinburgh

Ridding MC, Inzelberg R, Rothwell JC (1995) Changes in excitability of motor cortical circuitry in patients with Parkinson’s disease. Ann Neurol 37:181–188. doi:10.1002/ana.410370208 CrossRefPubMed

Rossi S, Hallett M, Rossini PM, Pascual-Leone A (2009) Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research. Clin Neurophysiol 120:2008–2039. doi:10.1016/j.clinph.2009.08.016 CrossRefPubMedPubMedCentral

Schabrun SM, Christensen SW, Mrachacz-Kersting N, Graven-Nielsen T (2015) Motor cortex reorganization and impaired function in the transition to sustained muscle pain. Cereb Cortex. doi:10.1093/cercor/bhu319 PubMed

Schneider C, Lavoie BA, Barbeau H, Capaday C (2004) Timing of cortical excitability changes during the reaction time of movements superimposed on tonic motor activity. J Appl Physiol 97:2220–2227CrossRefPubMed

Schwenkreis P, Janssen F, Rommel O et al (2003) Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand. Neurology 61:515–519CrossRefPubMed

Schwenkreis P, Scherens A, Ronnau A-K, Hoffken O, Tegenthoff M, Maier C (2010) Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain. BMC Neurosci 11:73CrossRefPubMedPubMedCentral

Seminowicz DA, Wideman TH, Naso L et al. (2011) Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J Neurosci 31:7540–7550 doi:10.1523/JNEUROSCI.5280-10.2011 CrossRefPubMed

Shirota Y, Hamada M, Terao Y et al (2010) Influence of short-interval intracortical inhibition on short-interval intracortical facilitation in human primary motor cortex. J Neurophysiol 104:1382–1391. doi:10.1152/jn.00164.2010 CrossRefPubMed

Stinear CM, Byblow WD (2003) Role of intracortical inhibition in selective hand muscle activation. J Neurophysiol 89:2014–2020. doi:10.1152/jn.00925.200200925.2002 CrossRefPubMed

Stokes IA, Henry SM, Single RM (2003) Surface EMG electrodes do not accurately record from lumbar multifidus muscles. Clin Biomech 18:9–13CrossRef

Stokes M, Hides J, Elliott J, Kiesel K, Hodges P (2007) Rehabilitative ultrasound imaging of the posterior paraspinal muscles. J Orthop Sports Phys Ther 37:581–595CrossRefPubMed

Strutton PH, Catley M, McGregor AH, Davey NJ (2003) Corticospinal excitability in patients with unilateral sciatica. Neurosci Lett 353:33–36CrossRefPubMed

Strutton PH, Beith ID, Theodorou S, Catley M, McGregor AH, Davey NJ (2004) Corticospinal activation of internal oblique muscles has a strong ipsilateral component and can be lateralised in man. In: Experimental brain research, vol 158. Springer, Berlin, pp 474–479

Strutton PH, Theodorou S, Catley M, McGregor AH, Davey NJ (2005) Corticospinal excitability in patients with chronic low back pain. J Spinal Disord Tech 18:420–424CrossRefPubMed

Symonds LL, Gordon NS, Bixby JC, Mande MM (2006) Right-lateralized pain processing in the human cortex: an FMRI study. J Neurophysiol 95:3823–3830. doi:10.1152/jn.01162.2005 CrossRefPubMed

Teyhen DS, Williamson JN, Carlson NH et al (2009) Ultrasound characteristics of the deep abdominal muscles during the active straight leg raise test. Arch Phys Med Rehabil 90:761–767. doi:10.1016/j.apmr.2008.11.011S0003-9993(09)00120-8 CrossRefPubMed

Tokimura H, Ridding MC, Tokimura Y, Amassian VE, Rothwell JC (1996) Short latency facilitation between pairs of threshold magnetic stimuli applied to human motor cortex. Electroencephalogr Clin Neurophysiol 101:263–272CrossRefPubMed

Tsao H, Galea MP, Hodges PW (2008) Reorganization of the motor cortex is associated with postural control deficits in recurrent low back pain. Brain 131:2161–2171. doi:10.1093/brain/awn154 CrossRefPubMed

Tsao H, Galea MP, Hodges PW (2010) Driving plasticity in the motor cortex in recurrent low back pain. Eur J Pain 14:832–839. doi:10.1016/j.ejpain.2010.01.001 CrossRefPubMed

Tsao H, Danneels L, Hodges PW (2011a) Individual fascicles of the paraspinal muscles are activated by discrete cortical networks in humans. Clin Neurophysiol 122:1580–1587. doi:10.1016/j.clinph.2011.01.048 CrossRefPubMed

Tsao H, Danneels LA, Hodges PW (2011b) ISSLS prize winner: smudging the motor brain in young adults with recurrent low back pain. Spine (Phila Pa 1976) 36:1721–1727. doi:10.1097/BRS.0b013e31821c4267 CrossRef

van Dieen JH, Selen LP, Cholewicki J (2003) Trunk muscle activation in low-back pain patients, an analysis of the literature. J Electromyogr Kinesiol 13:333–351CrossRefPubMed

Van K, Hides JA, Richardson CA (2006) The use of real-time ultrasound imaging for biofeedback of lumbar multifidus muscle contraction in healthy subjects. J Orthop Sports Phys Ther 36:920–925CrossRefPubMed

Wagle-Shukla A, Ni Z, Gunraj CA, Bahl N, Chen R (2009) Effects of short interval intracortical inhibition and intracortical facilitation on short interval intracortical facilitation in human primary motor cortex. J Physiol 587:5665–5678. doi:10.1113/jphysiol.2009.181446 CrossRefPubMedPubMedCentral

Wallwork TL, Hides JA, Stanton WR (2007) Intrarater and interrater reliability of assessment of lumbar multifidus muscle thickness using rehabilitative ultrasound imaging. J Orthop Sports Phys Ther 37:608–612CrossRefPubMed

Wallwork TL, Stanton WR, Freke M, Hides JA (2009) The effect of chronic low back pain on size and contraction of the lumbar multifidus muscle. Man Ther 14:496–500. doi:10.1016/j.math.2008.09.006 CrossRefPubMed

Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J (1999) Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol 517(Pt 2):591–597CrossRefPubMedPubMedCentral

Whittaker JL (2007) Ultrasound imaging for rehabilitation of the lumbopelvic region: a clinical approach. Churchill Livingstone, Philadelphia

Ziemann U, Tergau F, Wassermann EM, Wischer S, Hildebrandt J, Paulus W (1998) Demonstration of facilitatory I wave interaction in the human motor cortex by paired transcranial magnetic stimulation. J Physiol 511(Pt 1):181–190CrossRefPubMedPubMedCentral

Ziemann U, Muellbacher W, Hallett M, Cohen LG (2001) Modulation of practice-dependent plasticity in human motor cortex. Brain 124:1171–1181CrossRefPubMed

Ziemann U, Reis J, Schwenkreis P, Rosanova M, Strafella A, Badawy R, Muller-Dahlhaus F (2014) TMS and drugs revisited 2014. Clin Neurophysiol. doi:10.1016/j.clinph.2014.08.028

Titel: Corticomotor control of lumbar multifidus muscles is impaired in chronic low back pain: concurrent evidence from ultrasound imaging and double-pulse transcranial magnetic stimulation
verfasst von: Hugo Massé-Alarie
Louis-David Beaulieu
Richard Preuss
Cyril Schneider
Publikationsdatum: 01.04.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Experimental Brain Research / Ausgabe 4/2016
Print ISSN: 0014-4819
Elektronische ISSN: 1432-1106
DOI: https://doi.org/10.1007/s00221-015-4528-x

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