Dolor neuropático posterior a lesión de la médula espinal: el impacto de la actividad sensoriomotora.
Publicado originalmante en PAIN 158 (2017) 371–376.
DOI:
https://doi.org/10.47924/neurotarget2018132Palabras clave:
Dolor neuropático, lesión medular, actividad sensoriomotoraResumen
La lesión medular (LM) resulta en una severa disfunción motora, sensorial y autonómica seguida frecuentemente por espasticidad y dolor neuropático (DN). El DN puede surgir como resultado directo del daño sobre el sistema nervioso sensoriomotor periférico o central. Un estudio prospectivo que aplicó la nueva clasificación del dolor por lesión medular reportó dolor en el 80% de los pacientes con LM traumática. La evidencia emergente apoya la actividad sensoriomotora como un enfoque beneficioso para la modulación del DN tanto en animales como en humanos.
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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;54:973–79.
Ataoglu E, Tiftik T, Kara M, Tunc H, Ersoz M, Akkus S. Effects of chronic pain on quality of life and depression in patients with spinal cord injury. Spinal Cord 2013;51:23–6.
Baastrup C, Finnerup NB. Pharmacological management of neuropathic pain following spinal cord injury. CNS Drugs 2008;22:455–75.
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009;139:267–84.
Basbaum AI, Fields HL. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 1984;7:309–38.
Bavencoffe A, Li Y,Wu Z, Yang Q, Herrera J, Kennedy EJ, Walters ET. Persistent electrical activity in primary nociceptors after spinal cord injury is maintained by Scaffolded Adenylyl Cyclase and Protein Kinase A and is associated with altered Adenylyl Cyclase regulation. J Neurosci 2016;36:1660–8.
Beaumont E, Kaloustian S, Rousseau G, Cormery B. Training improves the electrophysiological properties of lumbar neurons and locomotion after thoracic spinal cord injury in rats. Neurosci Res 2008;62:147–54.
Boroujerdi A, Zeng J, Sharp K, Kim D, Steward O, Luo ZD. Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states. PAIN 2011;152:649–55.
Boyce VS, Mendell LM. Neurotrophins and spinal circuit function. Front Neural Circuits 2014;8:59.
Brown A, Ricci MJ, Weaver LC. NGF message and protein distribution in the injured rat spinal cord. Exp Neurol 2004;188:115–27.
Bryce TN, Biering-Sorensen F, Finnerup NB, Cardenas DD, Defrin R, Lundeberg T,Norrbrink C, Richards JS, Siddall P, Stripling T, Treede RD, Waxman SG, Widerstrom-Noga E, Yezierski RP, Dijkers M. International spinal cord injury pain classification: part I. Background and description. March 6–7, 2009. Spinal Cord 2012;50:413–17.
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.
Carlton SM, Du J, Tan HY, Nesic O, Hargett GL, Bopp AC, Yamani A, Lin Q, Willis WD, Hulsebosch CE. Peripheral and central sensitization in remote spinal cord regions contribute to central neuropathic pain after spinal cord injury. PAIN 2009;147:265–76.
Chen YW, Hsieh PL, Chen YC, Hung CH, Cheng JT. Physical exercise induces excess hsp72 expression and delays the development of hyperalgesia and allodynia in painful diabetic neuropathy rats. Anesth Analg 2013;116:482–90.
Chen YW, Lin MF, Chen YC, Hung CH, Tzeng JI, Wang JJ. Exercise training attenuates postoperative pain and expression of cytokines and N-methyl-D-aspartate receptor subunit 1 in rats. Reg Anesth Pain Med 2013;38:282–8.
Chopek JW, MacDonell CW, Gardiner K, Gardiner PF. Daily passive cycling attenuates the hyperexcitability and restores the responsiveness of the extensor monosynaptic reflex to quipazine in the chronic spinally transected rat. J Neurotrauma 2014;31:1083–7.
Cobianchi S, Casals-Diaz L, Jaramillo J, Navarro X. Differential effects of activity dependent treatments on axonal regeneration and neuropathic pain after peripheral nerve injury. Exp Neurol 2013;240:157–67.
Cobianchi S,Marinelli S, Florenzano F, Pavone F, Luvisetto S. Short- but not long-lasting treadmill running reduces allodynia and improves functional recovery after peripheral nerve injury. Neuroscience 2010;168:273–87.
Costigan M, Moss A, Latremoliere A, Johnston C, Verma-Gandhu M, Herbert TA, Barrett L, Brenner GJ, Vardeh D, Woolf CJ, Fitzgerald M. T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J Neurosci 2009; 29:14415–22.
Cote MP, Azzam GA, Lemay MA, Zhukareva V, Houle JD. Activitydependent increase in neurotrophic factors is associated with an enhanced modulation of spinal reflexes after spinal cord injury. J Neurotrauma 2011;28:299–309.
Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 2005;438: 1017–21.
Coull JA, Boudreau D, Bachand K, Prescott SA, Nault F, Sik A, De Koninck P, De Koninck Y. Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 2003;424:938–42.
Cruciger O, Schildhauer TA,Meindl RC, Tegenthoff M, Schwenkreis P, Citak M, Aach M. Impact of locomotion training with a neurologic controlled hybrid assistive limb (HAL) exoskeleton on neuropathic pain and health related quality of life (HRQoL) in chronic SCI: a case study. Disabil Rehabil Assist Technol 2014:1–6.
Detloff MR, Fisher LC, McGaughy V, Longbrake EE, Popovich PG, Basso DM. Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats. Exp Neurol 2008;212:337–47.
Detloff MR, Quiros-Molina D, Javia AS,Daggubati L, Nehlsen AD, Naqvi A, Ninan V, Vannix KN, McMullen MK, Amin S, Ganzer PD, Houle JD. Delayed exercise is ineffective at reversing aberrant nociceptive afferent plasticity or neuropathic pain after spinal cord injury in rats. Neurorehabil Neural Repair 2016;30:685–700.
Detloff MR, Smith EJ, Quiros Molina D, Ganzer PD, Houle JD. Acute exercise prevents the development of neuropathic pain and the sprouting of non-peptidergic (GDNF- and artemin-responsive) c-fibers after spinal cord injury. Exp Neurol 2014;255:38–48.
Ditor DS, Latimer AE, Ginis KA, Arbour KP, McCartney N, Hicks AL. Maintenance of exercise participation in individuals with spinal cord injury: effects on quality of life, stress and pain. Spinal Cord 2003;41:446–50.
Dobson JL, McMillan J, Li L. Benefits of exercise intervention in reducing neuropathic pain. Front Cell Neurosci 2014;8:102.
Dolbow DR, Gorgey AS, Ketchum JM, Gater DR. Homebased functional electrical stimulation cycling enhances quality of life in individuals with spinal cord injury. Top Spinal Cord Inj Rehabil 2013;19: 324–9.
Drew GM, Siddall PJ, Duggan AW. Responses of spinal neurones to cutaneous and dorsal root stimuli in rats with mechanical allodynia after contusive spinal cord injury. Brain Res 2001;893:59–69.
Drew GM, Siddall PJ, Duggan AW. Mechanical allodynia following contusion injury of the rat spinal cord is associated with loss of GABAergic inhibition in the dorsal horn. PAIN 2004;109:379–88.
Dugan EA, Sagen J. An intensive locomotor training paradigm improves neuropathic pain following spinal cord compression injury in rats. J Neurotrauma 2015;32:622–32.
Eaton MJ, Wolfe SQ, Martinez M, Hernandez M, Furst C, Huang J, Frydel BR, Gomez-Marin O. Subarachnoid transplant of a human neuronal cell line attenuates chronic allodynia and hyperalgesia after excitotoxic spinal cord injury in the rat. J Pain 2007;8:33–50.
Endo T, Ajiki T, Inoue H, Kikuchi M, Yashiro T, Nakama S, Hoshino Y, Murakami T, Kobayashi E. Early exercise in spinal cord injured rats induces allodynia through TrkB signaling. Biochem Biophys Res Commun 2009;381:339–44.
Finnerup NB. Pain in patients with spinal cord injury. PAIN 2013;154 (suppl 1):S71–76.
Finnerup NB,Gyldensted C, Fuglsang-Frederiksen A,Bach FW, Jensen TS. Sensory perception in complete spinal cord injury. Acta Neurol Scand 2004;109:194–9.
Finnerup NB, Jensen MP, Norrbrink C, Trok K, Johannesen IL, Jensen TS, Werhagen L. A prospective study of pain and psychological functioning following traumatic spinal cord injury. Spinal Cord 2016;54:816–21.
Finnerup NB, Norrbrink C, Trok K, Piehl F, Johannesen IL, Sorensen JC, Jensen TS,Werhagen L. Phenotypes and predictors of pain following traumatic spinal cord injury: a prospective study. J Pain 2014;15: 40–8.
Gomez-Pinilla F, Ying Z, Roy RR, Molteni R, Edgerton VR. Voluntary exercise induces a BDNF-mediated mechanism that promotes neuroplasticity. J Neurophysiol 2002;88:2187–95.
Griffin L, Decker MJ, Hwang JY, Wang B, Kitchen K, Ding Z, Ivy JL. Functional electrical stimulation cycling improves body composition, metabolic and neural factors in persons with spinal cord injury. J Electromyogr Kinesiol 2009;19:614–22.
Gwak YS, Hulsebosch CE. Upregulation of Group I metabotropic glutamate receptors in neurons and astrocytes in the dorsal horn following spinal cord injury. Exp Neurol 2005;195:236–43.
Gwak YS, Hulsebosch CE. Remote astrocytic and microglial activation modulates neuronal hyperexcitability and below-level neuropathic pain after spinal injury in rat. Neuroscience 2009;161:895–903.
Gwak YS, Kang J, Leem JW, Hulsebosch CE. Spinal AMPA receptor inhibition attenuates mechanical allodynia and neuronal hyperexcitability following spinal cord injury in rats. J Neurosci Res 2007;85:2352–9.
Gwak YS, Tan HY, Nam TS, Paik KS, Hulsebosch CE, Leem JW. Activation of spinal GABA receptors attenuates chronic central neuropathic pain after spinal cord injury. J Neurotrauma 2006;23: 1111–24.
Hagg T. Collateral sprouting as a target for improved function after spinal cord injury. J Neurotrauma 2006;23:281–94.
Hains BC, Klein JP, Saab CY, Craner MJ, Black JA, Waxman SG. Upregulation of sodium channel Nav1.3 and functional involvement in neuronal hyperexcitability associated with central neuropathic pain after spinal cord injury. J Neurosci 2003;23:8881–92.
Hains BC, Saab CY, Waxman SG. Changes in electrophysiological properties and sodium channel Nav1.3 expression in thalamic neurons after spinal cord injury. Brain 2005;128(Pt 10):2359–71.
Hains BC, Waxman SG. Activated microglia contribute to the maintenance of chronic pain after spinal cord injury. J Neurosci 2006; 26:4308–17.
Hains BC, Willis WD, Hulsebosch CE. Serotonin receptors 5-HT1A and 5-HT3 reduce hyperexcitability of dorsal horn neurons after chronic spinal cord hemisection injury in rat. Exp Brain Res 2003;149:174–86.
Hansen CN, Fisher LC, Deibert RJ, Jakeman LB, Zhang H, Noble- Haeusslein L, White S, Basso DM. Elevated MMP-9 in the lumbar cord early after thoracic spinal cord injury motor relearning in mice. J Neurosci 2013;33:13101–11.
Heinricher MM, Tavares I, Leith JL, Lumb BM. Descending control of nociception: specificity, recruitment and plasticity. Brain Res Rev 2009; 60:214–25.
Hicks AL, Martin KA, Ditor DS, Latimer AE, Craven C, Bugaresti J, McCartney N. Long-term exercise training in persons with spinal cord injury: effects on strength, arm ergometry performance and psychological well-being. Spinal Cord 2003;41:34–43.
Houle JD, Cote MP. Axon regeneration and exercise-dependent plasticity after spinal cord injury. Ann N Y Acad Sci 2013;1279:154–63.
Hutchinson KJ, Gomez-Pinilla F, Crowe MJ, Ying Z, Basso DM. Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. Brain 2004;127(Pt 6):1403–14.
Jung SY, Kim DY, Yune TY, Shin DH, Baek SB, Kim CJ. Treadmill exercise reduces spinal cord injury-induced apoptosis by activating the PI3K/Akt pathway in rats. Exp Ther Med 2014;7:587–93.
Kakulas BA. A review of the neuropathology of human spinal cord injury with emphasis on special features. J Spinal Cord Med 1999;22:119–24.
Kerr BJ, David S. Pain behaviors after spinal cord contusion injury in two commonly used mouse strains. Exp Neurol 2007;206:240–7.
Krenz NR, Weaver LC. Sprouting of primary afferent fibers after spinal cord transection in the rat. Neuroscience 1998;85:443–58.
Kressler J, Thomas CK, Field-Fote EC, Sanchez J, WiderstromNoga E, Cilien DC, Gant K, Ginnety K, Gonzalez H, Martinez A, Anderson KD, Nash MS. Understanding therapeutic benefits of overground bionic ambulation: exploratory case series in persons with chronic, complete spinal cord injury. Arch Phys Med Rehabil 2014;95:1878–87.e1874.
Liu D, Thangnipon W, McAdoo DJ. Excitatory amino acids rise to toxic levels upon impact injury to the rat spinal cord. Brain Res 1991;547:344–8.
Lu Y, Zheng J, Xiong L, Zimmermann M, Yang J. Spinal cord injuryinduced attenuation of GABAergic inhibition in spinal dorsal horn circuits is associated with down-regulation of the chloride transporter KCC2 in rat. J Physiol 2008;586(Pt 23):5701–15.
Lundbye-Jensen J, Nielsen JB. Immobilization induces changes in presynaptic control of group Ia afferents in healthy humans. J Physiol 2008;586(Pt 17):4121–35.
Meisner JG, Marsh AD, Marsh DR. Loss of GABAergic interneurons in laminae I-III of the spinal cord dorsal horn contributes to reduced GABAergic tone and neuropathic pain after spinal cord injury. J Neurotrauma 2010;27:729–37.
Molteni R, Zheng JQ, Ying Z, Gomez-Pinilla F, Twiss JL. Voluntary exercise increases axonal regeneration from sensory neurons. Proc Natl Acad Sci U S A 2004;101:8473–8.
Neefkes-Zonneveld CR, Bakkum AJ, Bishop NC, van Tulder MW, Janssen TW. Effect of long-term physical activity and acute exercise on markers of systemic inflammation in persons with chronic spinal cord injury: a systematic review. Arch Phys Med Rehabil 2015;96:30–42.
Nees TA, Tappe-Theodor A, Sliwinski C, Motsch M, Rupp R, Kuner R, Weidner N, Blesch A. Early-onset treadmill training reduces mechanical allodynia and modulates calcitonin gene-related peptide fiber density in lamina III/IV in a mouse model of spinal cord contusion injury.PAIN 2016;157:687–97.
Norrbrink C, Lindberg T, Wahman K, Bjerkefors A. Effects of an exercise programme on musculoskeletal and neuropathic pain after spinal cord injury–results from a seated double-poling ergometer study. Spinal Cord 2012;50:457–61.
Norrbrink C, Lundeberg T. Tramadol in neuropathic pain after spinal cord injury: a randomized, double-blind, placebo-controlled trial. Clin J Pain 2009;25:177–84.
O’Donnell J, Zeppenfeld D, McConnell E, Pena S, Nedergaard M. Norepinephrine: a neuromodulator that boosts the function of multiple cell types to optimize CNS performance. Neurochem Res 2012;37:2496–512.
Ondarza AB, Ye Z, Hulsebosch CE. Direct evidence of primary afferent sprouting in distant segments following spinal cord injury in the rat: colocalization of GAP-43 and CGRP. Exp Neurol 2003;184:373–80.
Putzke JD, Richards JS, Hicken BL, DeVivo MJ. Interference due to pain following spinal cord injury: important predictors and impact on quality of life. PAIN 2002;100:231–42.
Ramer MS, Priestley JV, McMahon SB. Functional regeneration of sensory axons into the adult spinal cord. Nature 2000;403:312–16.
Reese NB, Skinner RD, Mitchell D, Yates C, Barnes CN, Kiser TS, Garcia-Rill E. Restoration of frequency-dependent depression of the Hreflex by passive exercise in spinal rats. Spinal Cord 2006;44:28–34.
Rintala DH, Holmes SA, Courtade D, Fiess RN, Tastard LV, Loubser PG. Comparison of the effectiveness of amitriptyline and gabapentin on chronic neuropathic pain in persons with spinal cord injury. Arch Phys Med Rehabil 2007;88:1547–60.
Rupp R, Schließmann D, Plewa H, Schuld C, Gerner HJ, Weidner N, Hofer EP, Knestel M. Safety and efficacy of at-home robotic locomotion therapy in individuals with chronic incomplete spinal cord injury: a prospective, pre-post intervention study. PLoS One 2015;10:e0119167.
Sandrow-Feinberg HR, Izzi J, Shumsky JS, Zhukareva V, Houle JD. Forced exercise as a rehabilitation strategy after unilateral cervical spinal cord contusion injury. J Neurotrauma 2009;26:721–31.
Schmitt AB, Buss A, Breuer S, Brook GA, Pech K, Martin D, Schoenen J, Noth J, Love S, Schroder JM, Kreutzberg GW, Nacimiento W. Major histocompatibility complex class II expression by activated microglia caudal to lesions of descending tracts in the human spinal cord is not associated with a T cell response. Acta Neuropathol 2000;100:528–36.
Shin HY, Kim H, Kwon MJ, Hwang DH, Lee K, Kim BG. Molecular and cellular changes in the lumbar spinal cord following thoracic injury: regulation by treadmill locomotor training. PLoS One 2014;9:e88215.
Siddall PJ. Management of neuropathic pain following spinal cord injury: now and in the future. Spinal Cord 2009;47:352–9.
Siddall PJ, Cousins MJ, Otte A, Griesing T, Chambers R, Murphy TK. Pregabalin in central neuropathic pain associated with spinal cord injury: a placebo-controlled trial. Neurology 2006;67:1792–800.
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;103:249–57.
Stagg NJ,Mata HP, Ibrahim MM, Henriksen EJ, Porreca F, Vanderah TW, Philip Malan T Jr. Regular exercise reverses sensory hypersensitivity in a rat neuropathic pain model: role of endogenous opioids. Anesthesiology 2011; 114:940–8.
Terkelsen AJ, Bach FW, Jensen TS. Experimental forearm immobilization in humans induces cold and mechanical hyperalgesia. Anesthesiology 2008;109:297–307.
Trierweiler J, Gottert DN, Gehlen G. Evaluation of mechanical allodynia in an animal immobilization model using the von frey method. J Manipulative Physiol Ther 2012;35:18–25.
Turiel M, Sitia S, Cicala S, Magagnin V, Bo I, Porta A, Caiani E, Ricci C, Licari V, De Gennaro Colonna V, Tomasoni L. Robotic treadmill training improves cardiovascular function in spinal cord injury patients. Int J Cardiol 2011;149:3239.
Vaynman S, Gomez-Pinilla F. License to run: exercise impacts functional plasticity in the intact and injured central nervous system by using neurotrophins. Neurorehabil Neural Repair 2005;19:283–95.
Walters ET. Neuroinflammatory contributions to pain after SCI: roles for central glial mechanisms and nociceptor-mediated host defense. Exp Neurol 2014;258:48–61.
Ward PJ, Herrity AN, Smith RR, Willhite A, Harrison BJ, Petruska JC, Harkema SJ, Hubscher CH. Novel multi-system functional gains via task specific training in spinal cord injured male rats. J Neurotrauma 2014;31: 819–33.
Weaver LC, Verghese P, Bruce JC, Fehlings MG, Krenz NR, Marsh DR. Autonomic dysreflexia and primary afferent sprouting after clipcompression injury of the rat spinal cord. J Neurotrauma 2001;18:1107–19.
Weishaupt N, Blesch A, Fouad K. BDNF: the career of a multifaceted neurotrophin in spinal cord injury. Exp Neurol 2012;238:254–64.
Werhagen L, Budh CN, Hultling C, Molander C. Neuropathic pain after traumatic spinal cord injury–relations to gender, spinal level, completeness, and age at the time of injury. Spinal Cord 2004;42:665–73.
Widerstrom-Noga EG, Felipe-Cuervo E, Yezierski RP. Chronic pain after spinal injury: interference with sleep and daily activities. Arch Phys Med Rehabil 2001;82:1571–7.
Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. PAIN 2011;152(suppl 3):S2–15.
Wu Z, Yang Q, Crook RJ, O’Neil RG, Walters ET. TRPV1 channels make major contributions to behavioral hypersensitivity and spontaneous activity in nociceptors after spinal cord injury. PAIN 2013;154:2130–41.
Yang Q, Wu Z, Hadden JK, Odem MA, Zuo Y, Crook RJ, Frost JA, Walters ET. Persistent pain after spinal cord injury is maintained by primary afferent activity. J Neurosci 2014;34:10765–9.
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(Pt 2):418–30.
Zhao P, Waxman SG, Hains BC. Extracellular signal-regulated kinaseregulated microglia-neuron signaling by prostaglandin E2 contributes to pain after spinal cord injury. J Neurosci 2007;27:2357–68.
Zinck ND, Rafuse VF, Downie JW. Sprouting of CGRP primary afferents in lumbosacral spinal cord precedes emergence of bladder activity after spinal injury. Exp Neurol 2007;204:777–90.
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Derechos de autor 2018 Timo A. Nees, Nanna B.Finnerup, Armin Blesch, Norbert Weidner
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