Abstract
Study design:
The 2016 International Spinal Cord Society Sir Ludwig Guttmann Lecture.
Objectives:
The aim of this review is to identify different symptoms and signs of neuropathic pain and spasticity after spinal cord injury (SCI) and to present different methods of assessing them. The objective is to discuss how a careful characterization of different symptoms and signs, and a better translation of preclinical findings may improve our understanding of the complex and entangled mechanisms of neuropathic pain and spasticity.
Methods:
A MEDLINE search was performed using the following terms: ‘pain’, ‘neuropathic’, ‘spasticity’, ‘spasms’ and ‘spinal cord injury’.
Results:
This review identified different domains of neuropathic pain and spasticity after SCI and methods to assess them in preclinical and clinical research. Different factors important for pain description include location, onset, pain descriptors and somatosensory function, while muscle tone, spasms, reflexes and clonus are important aspects of spasticity. Similarities and differences between neuropathic pain and spasticity are discussed.
Conclusions:
Understanding that neuropathic pain and spasticity are multidimensional consequences of SCI, and a careful examination and characterization of the symptoms and signs, are a prerequisite for understanding the relationship between neuropathic pain and spasticity and the intricate underlying mechanisms.
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References
Brown A, Weaver LC . The dark side of neuroplasticity. Exp Neurol 2012; 235: 133–141.
Widerstrom-Noga EG, Felipe-Cuervo E, Yezierski RP . Chronic pain after spinal injury: Interference with sleep and daily activities. Arch Phys Med Rehabil 2001; 82: 1571–1577.
Westerkam D, Saunders LL, Krause JS . Association of spasticity and life satisfaction after spinal cord injury. Spinal Cord 2011; 49: 990–994.
Lundstrom U, Wahman K, Seiger A, Gray DB, Isaksson G, Lilja M . Participation in activities and secondary health complications among persons aging with traumatic spinal cord injury. Spinal Cord 2016; 55: 367–372.
Andresen SR, Biering-Sorensen F, Hagen EM, Nielsen JF, Bach FW, Finnerup NB . Pain, spasticity and quality of life in individuals with traumatic spinal cord injury in Denmark. Spinal Cord 2016; 54: 973–979.
Adriaansen JJ, Ruijs LE, van Koppenhagen CF, van Asbeck FW, Snoek GJ, van KD et al. Secondary health conditions and quality of life in persons living with spinal cord injury for at least ten years. J Rehabil Med 2016; 48: 853–860.
Rubinelli S, Glassel A, Brach M . From the person's perspective: Perceived problems in functioning among individuals with spinal cord injury in Switzerland. J Rehabil Med 2016; 48: 235–243.
Siddall PJ, McClelland JM, Rutkowski SB, Cousins MJ . A longitudinal study of the prevalence and characteristics of pain in the first 5 years following spinal cord injury. Pain 2003; 103: 249–257.
Holtz KA, Lipson R, Noonan VK, Kwon BK, Mills PB . The prevalence and effect of problematic spasticity following traumatic spinal cord injury. Arch Phys Med Rehabil 2016; 98: 1132–1138.
Finnerup NB, Jensen MP, Norrbrink C, Trok K, Johannesen IL, Jensen TS et al. A prospective study of pain and psychological functioning following traumatic spinal cord injury. Spinal Cord 2016; 51: 816–821.
Burke D, Fullen BM, Stokes D, Lennon O . Neuropathic pain prevalence following spinal cord injury: A systematic review and meta-analysis. Eur J Pain 2017; 21: 29–44.
Jensen TS, Baron R, Haanpaa M, Kalso E, Loeser JD, Rice AS et al. A new definition of neuropathic pain. Pain 2011; 152: 2204–2205.
Finnerup NB, Haroutounian S, Kamerman P, Baron R, Bennett DL, Bouhassira D et al. Neuropathic pain: an updated grading system for research and clinical practice. Pain 2016; 157: 1599–1606.
Bryce TN, Biering-Sorensen F, Finnerup NB, Cardenas DD, Defrin R, Lundeberg T et al. International spinal cord injury pain (ISCIP) classification: part I. background and description. Spinal Cord 2012; 50: 413–417.
Pandyan AD, Gregoric M, Barnes MP, Wood D, Van WF, Burridge J et al. Spasticity: clinical perceptions, neurological realities and meaningful measurement. Disabil Rehabil 2005; 27: 2–6.
Biering-Sorensen F, Burns AS, Curt A, Harvey LA, Jane MM, Nance PW et al. International spinal cord injury musculoskeletal basic data set. Spinal Cord 2012; 50: 797–802.
Lance WL "Symposium Synopsis,"in. Spasticity: Disorderd Motor Control Feldman RG, Young RR, Koella WP eds. Symposia Specialists INC. MEdical books: Chicago, IL, USA. 1980, 485–494.
Nielsen JB, Crone C, Hultborn H . The spinal pathophysiology of spasticity—from a basic science point of view. Acta Physiol 2007; 189: 171–180.
Sjolund BH . Pain and rehabilitation after spinal cord injury: the case of sensory spasticity? Brain Res Brain Res Rev 2002; 40: 250–256.
Mueller ME, Gruenthal M, Olson WL, Olson WH . Gabapentin for relief of upper motor neuron symptoms in multiple sclerosis. Arch Phys Med Rehabil 1997; 78: 521–524.
Braid JJ, Kirker SG, Baguley IJ . Spasticity increases during pregabalin withdrawal. Brain Inj 2013; 27: 120–124.
Canavero S, Bonicalzi V . Intravenous subhypnotic propofol in central pain: a double-blind, placebo-controlled, crossover study. Clin Neuropharmacol 2004; 27: 182–186.
Besson M, Matthey A, Daali Y, Poncet A, Vuilleumier P, Curatolo M et al. GABAergic modulation in central sensitization in humans: a randomized placebo-controlled pharmacokinetic-pharmacodynamic study comparing clobazam with clonazepam in healthy volunteers. Pain 2015; 156: 397–404.
Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 162–173.
Cardenas DD, Warms CA, Turner JA, Marshall H, Brooke MM, Loeser JD . Efficacy of amitriptyline for relief of pain in spinal cord injury: results of a randomized controlled trial. Pain 2002; 96: 365–373.
Shaikh A, Phadke CP, Ismail F, Boulias C . Relationship between botulinum toxin, spasticity, and pain: a survey of patient perception. Can J Neurol Sci 2016; 43: 311–315.
Priebe MM, Sherwood AM, Thornby JI, Kharas NF, Markowski J . Clinical assessment of spasticity in spinal cord injury: a multidimensional problem. Arch Phys Med Rehabil 1996; 77: 713–716.
Biering-Sorensen F, Nielsen JB, Klinge K . Spasticity-assessment: a review. Spinal Cord 2006; 44: 708–722.
Attal N, Bouhassira D, Baron R, Dostrovsky J, Dworkin RH, Finnerup N et al. Assessing symptom profiles in neuropathic pain clinical trials: Can it improve outcome? Eur J Pain 2011; 15: 441–443.
von Hehn CA, Baron R, Woolf CJ . Deconstructing the neuropathic pain phenotype to reveal neural mechanisms. Neuron 2012; 73: 638–652.
Finnerup NB, Norrbrink C, Trok K, Piehl F, Johannesen IL, Sorensen JC et al. Phenotypes and predictors of pain following traumatic spinal cord injury: a prospective study. J Pain 2014; 15: 40–48.
Zeilig G, Enosh S, Rubin-Asher D, Lehr B, Defrin R . The nature and course of sensory changes following spinal cord injury: predictive properties and implications on the mechanism of central pain. Brain 2012; 135: 418–430.
Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E et al. Development and validation of the Neuropathic Pain Symptom Inventory. Pain 2004; 108: 248–257.
Baron R, Maier C, Attal N, Binder A, Bouhassira D, Cruccu G et al. Peripheral Neuropathic Pain: A mechanism-related organizing principle based on sensory profiles. Pain 2017; 158: 261–272.
Widerstrom-Noga EG, Finnerup NB, Siddall PJ . Biopsychosocial perspective on a mechanisms-based approach to assessment and treatment of pain following spinal cord injury. J Rehabil Res Dev 2009; 46: 1–12.
Widerstrom-Noga E, Felix ER, Adcock JP, Escalona M, Tibbett J . Multidimensional neuropathic pain phenotypes after spinal cord injury. J Neurotrauma 2016; 33: 482–492.
Helfert SM, Reimer M, Hoper J, Baron R . Individualized pharmacological treatment of neuropathic pain. Clin Pharmacol Ther 2015; 97: 135–142.
Finnerup NB, Sindrup SH, Bach FW, Johannesen IL, Jensen TS . Lamotrigine in spinal cord injury pain: a randomized controlled trial. Pain 2002; 96: 375–383.
Demant DT, Lund K, Vollert J, Maier C, Segerdahl M, Finnerup NB et al. The effect of oxcarbazepine in peripheral neuropathic pain depends on pain phenotype: a randomised, double-blind, placebo-controlled phenotype-stratified study. Pain 2014; 155: 2263–2273.
Widerstrom-Noga E, Biering-Sorensen F, Bryce TN, Cardenas DD, Finnerup NB, Jensen MP et al. The International Spinal Cord Injury Pain Extended Data Set (Version 1.0). Spinal Cord 2016; 54: 1036–1046.
Kramer JL, Minhas NK, Jutzeler CR, Erskine EL, Liu LJ, Ramer MS . Neuropathic pain following traumatic spinal cord injury: Models, measurement, and mechanisms. J Neurosci Res 2016.
Percie, du SN, Rice AS . Improving the translation of analgesic drugs to the clinic: animal models of neuropathic pain. Br J Pharmacol 2014; 171: 2951–2963.
Davoody L, Quiton RL, Lucas JM, Ji Y, Keller A, Masri R . Conditioned place preference reveals tonic pain in an animal model of central pain. J Pain 2011; 12: 868–874.
Wodarski R, Delaney A, Ultenius C, Morland R, Andrews N, Baastrup C et al. Cross-centre replication of suppressed burrowing behaviour as an ethologically relevant pain outcome measure in the rat: a prospective multicentre study. Pain 2016; 157: 2350–2365.
Galan-Arriero I, Avila-Martin G, Ferrer-Donato A, Gomez-Soriano J, Bravo-Esteban E, Taylor J . Oral administration of the p38alpha MAPK inhibitor, UR13870, inhibits affective pain behavior after spinal cord injury. Pain 2014; 155: 2188–2198.
Baastrup C, Maersk-Moller CC, Nyengaard JR, Jensen TS, Finnerup NB . Spinal-, brainstem- and cerebrally mediated responses at- and below-level of a spinal cord contusion in rats: evaluation of pain-like behavior. Pain 2010; 151: 670–679.
Vierck CJ, Yezierski RP . Comparison of operant escape and reflex tests of nociceptive sensitivity. Neurosci Biobehav Rev 2015; 51: 223–242.
Vierck CJ, Light AR . in Spinal Cord Injury Pain: Assessment, Mechanisms, Management. Progress in Pain Research and Management. Yezierski RP, Burchiel KJ (eds) IASP Press: Seattle, WA, USA. 2002, 137–154.
Yezierski RP, Vierck CJ . Reflex and pain behaviors are not equivalent: lessons from spinal cord injury. Pain 2010; 151: 569–570.
van GS, Deumens R, Leerink M, Nguyen S, Joosten EA, Marsala M . Translation of the rat thoracic contusion model; part 1-supraspinally versus spinally mediated pain-like responses and spasticity. Spinal Cord 2014; 52: 524–528.
Hsieh JT, Wolfe DL, Miller WC, Curt A . Spasticity outcome measures in spinal cord injury: psychometric properties and clinical utility. Spinal Cord 2008; 46: 86–95.
Vierck CJ, Cannon RL, Stevens KA, Acosta-Rua AJ, Wirth ED . in Spinal Cord Injury Pain: Assessment, Mechanisms, Management. Progress in Pain Research and Management. Yezierski RP, Burchiel KJ (eds) IASP Press: Seattle, WA, USA. 2002, 155–173.
Ashworth B . Preliminary trial of carisoprodol in multiple sclerosis. Practitioner 1964; 192: 540–542.
Bohannon RW, Smith MB . Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther 1987; 67: 206–207.
Tardieu G, Shentoub S, Delarue R . [Research on a technic for measurement of spasticity]. Rev Neurol 1954; 91: 143–144.
Penn RD, Savoy SM, Corcos D, Latash M, Gottlieb G, Parke B et al. Intrathecal baclofen for severe spinal spasticity. N Engl J Med 1989; 320: 1517–1521.
Benz EN, Hornby TG, Bode RK, Scheidt RA, Schmit BD . A physiologically based clinical measure for spastic reflexes in spinal cord injury. Arch Phys Med Rehabil 2005; 86: 52–59.
Hiersemenzel LP, Curt A, Dietz V . From spinal shock to spasticity: neuronal adaptations to a spinal cord injury. Neurology 2000; 54: 1574–1582.
Eaton M . Common animal models for spasticity and pain. J Rehabil Res Dev 2003; 40: 41–54.
Corleto JA, Bravo-Hernandez M, Kamizato K, Kakinohana O, Santucci C, Navarro MR et al. Thoracic 9 spinal transection-induced model of muscle spasticity in the rat: a systematic electrophysiological and histopathological characterization. PLoS ONE 2015; 10: e0144642.
Tashiro S, Shinozaki M, Mukaino M, Renault-Mihara F, Toyama Y, Liu M et al. BDNF Induced by Treadmill training contributes to the suppression of spasticity and allodynia after spinal cord injury via upregulation of KCC2. Neurorehabil Neural Repair 2015; 29: 677–689.
Marsala M, Hefferan MP, Kakinohana O, Nakamura S, Marsala J, Tomori Z . Measurement of peripheral muscle resistance in rats with chronic ischemia-induced paraplegia or morphine-induced rigidity using a semi-automated computer-controlled muscle resistance meter. J Neurotrauma 2005; 22: 1348–1361.
Bennett DJ, Gorassini M, Fouad K, Sanelli L, Han Y, Cheng J . Spasticity in rats with sacral spinal cord injury. J Neurotrauma 1999; 16: 69–84.
Gonzenbach RR, Gasser P, Zorner B, Hochreutener E, Dietz V, Schwab ME . Nogo-A antibodies and training reduce muscle spasms in spinal cord-injured rats. Ann Neurol 2010; 68: 48–57.
Kathe C, Hutson TH, McMahon SB, Moon LD . Intramuscular Neurotrophin-3 normalizes low threshold spinal reflexes, reduces spasms and improves mobility after bilateral corticospinal tract injury in rats. Elife 2016; 5: e18146.
Dietz V, Sinkjaer T . Spasticity. Handb Clin Neurol 2012; 109: 197–211.
Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D et al. Neuropathic pain. Nat Rev Dis Primers 2017; 3: 17002.
Vierck CJ, Light AR . Allodynia and hyperalgesia within dermatomes caudal to a spinal cord injury in primates and rodents. Prog Brain Res 2000; 129: 411–428.
Vierck CJJ, Light AR . Effects of combined hemotoxic and anterolateral spinal lesions on nociceptive sensitivity. Pain 1999; 83: 447–457.
Finnerup NB, Johannesen IL, Fuglsang-Frederiksen A, Bach FW, Jensen TS . Sensory function in spinal cord injury patients with and without central pain. Brain 2003; 126: 57–70.
Finnerup NB, Sorensen L, Biering-Sorensen F, Johannesen IL, Jensen TS . Segmental hypersensitivity and spinothalamic function in spinal cord injury pain. Exp Neurol 2007; 207: 139–149.
Levitan Y, Zeilig G, Bondi M, Ringler E, Defrin R . Predicting the Risk for central pain using the sensory components of the international standards for neurological classification of spinal cord injury. J Neurotrauma 2015; 32: 1684–1692.
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NBF has received honoraria or travel support from Pfizer, Grünenthal, Astellas, Teva Pharmaceuticals, and Novartis Pharma and grants from IMI Europain (EU/EFPIA) outside the submitted work.
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This is a review in relation to The 2016 Sir Ludwig Guttmann Lecture at the 55th ISCoS Annual Scientific Meeting, Vienna, Austria.
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Finnerup, N. Neuropathic pain and spasticity: intricate consequences of spinal cord injury. Spinal Cord 55, 1046–1050 (2017). https://doi.org/10.1038/sc.2017.70
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DOI: https://doi.org/10.1038/sc.2017.70
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