Riluzole effects on behavioral sensitivity and the development of axonal damage and spinal modifications that occur after painful nerve root compression: Laboratory investigation

Journal of Neurosurgery: Spine

Volumn 20, Issue 6, 2014, Pages 751-762

  Nicholson, Kristen J ^a   Zhang, Sijia ^a   Gilliland, Taylor M ^a   Winkelstein, Beth A ^a,b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

GLT 1; Injury; Nerve root; Neuronal hyperexcitability; Pain; Radiculopathy; Riluzole; Spinal cord injury

Indexed keywords

CALCITONIN GENE RELATED PEPTIDE; ISOLECTIN B4; NEUROFILAMENT 200; NEUROFILAMENT PROTEIN; RILUZOLE; UNCLASSIFIED DRUG; VESICULAR GLUTAMATE TRANSPORTER 1;

ALLODYNIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINOCICEPTION; ARTICLE; AXONAL INJURY; CONTROLLED STUDY; DORSAL ROOT; DRUG EFFECT; ELECTROPHYSIOLOGICAL PROCEDURES; EVALUATION STUDY; EVOKED RESPONSE; EXCITABILITY; FOREFOOT; HYPERALGESIA; IMMUNOHISTOCHEMISTRY; LATENT PERIOD; MALE; MORPHOLOGY; MYELINATED NERVE; NERVE FIBER; NERVE FIBER DEGENERATION; NERVE FIBER TRANSPORT; NERVE ROOT; NERVE ROOT COMPRESSION; NEUROPROTECTION; NONHUMAN; PEPTIDERGIC NERVOUS SYSTEM; PROTEIN EXPRESSION; RAT; SINGLE DRUG DOSE; SPINAL CORD DORSAL HORN; SPINAL CORD TRANSSECTION;

CGRP = CALCITONIN GENE-RELATED PEPTIDE; GLT-1; HSD = HONESTLY SIGNIFICANT DIFFERENCE; IB4 = ISOLECTIN-B4; INJURY; LTM = LOW-THRESHOLD MECHANORECEPTIVE; NERVE ROOT; NEURONAL HYPEREXCITABILITY; NF200 = NEUROFILAMENT-200; PAIN; RADICULOPATHY; RILUZOLE; ROI = REGION OF INTEREST; SPINAL CORD INJURY; WDR = WIDE DYNAMIC RANGE;

ANIMALS; AXONS; HYPERALGESIA; IMMUNOHISTOCHEMISTRY; MALE; NECK INJURIES; NECK PAIN; NERVE COMPRESSION SYNDROMES; NEUROPROTECTIVE AGENTS; RADICULOPATHY; RATS; RATS, SPRAGUE-DAWLEY; RILUZOLE; SPINAL NERVE ROOTS;

EID: 84901783658     PISSN: 15475654     EISSN: 15475646     Source Type: Journal    
DOI: 10.3171/2014.2.SPINE13672     Document Type: Article

References (78)

1. Abbadie C, Brown JL, Mantyh PW, Basbaum AI: Spinal cord substance P receptor immunoreactivity increases in both inflammatory and nerve injury models of persistent pain. Neuroscience 70:201-209, 1996 (Pubitemid 126755236)
2. Abbed KM, Coumans JV: Cervical radiculopathy: pathophysiology, presentation, and clinical evaluation. Neurosurgery 60 (1 Supp1 1):S28-S34, 2007
3. Azbill RD, Mu X, Springer JE: Riluzole increases high-affinity glutamate uptake in rat spinal cord synaptosomes. Brain Res 871:175-180, 2000 (Pubitemid 30433869)
4. Basbaum AI, Bautista DM, Scherrer G, Julius D: Cellular and molecular mechanisms of pain. Cell 139:267-284, 2009
5. Bellingham MC: A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? CNS Neurosci Ther 17:4-31, 2011
6. Benediktsson AM, Marrs GS, Tu JC, Worley PF, Rothstein JD, Bergles DE, et al: Neuronal activity regulates glutamate transporter dynamics in developing astrocytes. Glia 60:175-188, 2012
7. Bennett AD, Chastain KM, Hulsebosch CE: Alleviation of mechanical and thermal allodynia by CGRP(8-37) in a rodent model of chronic central pain. Pain 86:163-175, 2000 (Pubitemid 30211715)
8. Carbone M, Duty S, Rattray M: Riluzole elevates GLT-1 activity and levels in striatal astrocytes. Neurochem Int 60:31-38, 2012
9. Carbone M, Duty S, Rattray M: Riluzole neuroprotection in a Parkinson's disease model involves suppression of reactive astrocytosis but not GLT-1 regulation. BMC Neurosci 13:38, 2012
10. Carette S, Fehlings MG: Clinical practice. Cervical radiculopathy. N Engl J Med 353:392-399, 2005
11. Cata JP, Weng HR, Chen JH, Dougherty PM: Altered discharges of spinal wide dynamic range neurons and down-regulation of glutamate transporter expression in rats with paclitaxel-induced hyperalgesia. Neuroscience 138:329-338, 2006 (Pubitemid 43222091)
12. Chang YW, Winkelstein BA: Schwann cell proliferation and macrophage infiltration are evident at day 14 after painful cervical nerve root compression in the rat. J Neurotrauma 28:2429-2438, 2011
13. Chao T, Pham K, Steward O, Gupta R: Chronic nerve compression injury induces a phenotypic switch of neurons within the dorsal root ganglia. J Comp Neurol 506:180-193, 2008
14. Christensen MD, Hulsebosch CE: Spinal cord injury and anti-NGF treatment results in changes in CGRP density and distribution in the dorsal horn in the rat. Exp Neurol 147:463-475, 1997 (Pubitemid 27497307)
15. Coderre TJ, Kumar N, Lefebvre CD, Yu JSC: A comparison of the glutamate release inhibition and anti-allodynic effects of gabapentin, lamotrigine, and riluzole in a model of neuropathic pain. J Neurochem 100:1289-1299, 2007
16. Colburn RW, Rickman AJ, DeLeo JA: The effect of site and type of nerve injury on spinal glial activation and neuropathic pain behavior. Exp Neurol 157:289-304, 1999 (Pubitemid 29260737)
17. Costa HJZR, da Silva CF, Costa MP, Lazarini PR: Evaluation of the systemic use of riluzole in post-traumatic facial nerve regeneration: experimental study in rabbits. Acta Otolaryngol 127:1222-1225, 2007 (Pubitemid 47610575)
18. Côté P, Cassidy JD, Carroll LJ, Kristman V: The annual incidence and course of neck pain in the general population: a population-based cohort study. Pain 112:267-273, 2004 (Pubitemid 39550726)
19. Crosby ND, Weisshaar CL, Winkelstein BA: Spinal neuronal plasticity is evident within 1 day after a painful cervical facet joint injury. Neurosci Lett 542:102-106, 2013
20. Dirig DM, Salami A, Rathbun ML, Ozaki GT, Yaksh TL: Characterization of variables defining hindpaw withdrawal latency evoked by radiant thermal stimuli. J Neurosci Methods 76:183-191, 1997 (Pubitemid 27428253)
21. Doble A: The pharmacology and mechanism of action of riluzole. Neurology 47 (6 Suppl 4):S233-S241, 1996
22. Fumagalli E, Funicello M, Rauen T, Gobbi M, Mennini T: Riluzole enhances the activity of glutamate transporters GLAST, GLT1 and EAAC1. Eur J Pharmacol 578:171-176, 2008 (Pubitemid 350309596)
23. Ghosh M, Yang Y, Rothstein JD, Robinson MB: Nuclear factor-κB contributes to neuron-dependent induction of glutamate transporter-1 expression in astrocytes. J Neurosci 31:9159-9169, 2011
24. Grossman RG, Fehlings MG, Frankowski RF, Burau KD, Chow DSL, Tator C, et al: A prospective, multicenter, phase I matched-comparison group trial of safety, pharmacokinetics, and preliminary efficacy of riluzole in patients with traumatic spinal cord injury. J Neurotrauma 31:239-255, 2014
25. Hains BC, Johnson KM, Eaton MJ, Willis WD, Hulsebosch CE: Serotonergic neural precursor cell grafts attenuate bilateral hyperexcitability of dorsal horn neurons after spinal hemisection in rat. Neuroscience 116:1097-1110, 2003 (Pubitemid 36262968)
26. Hama A, Sagen J: Antinociceptive effect of riluzole in rats with neuropathic spinal cord injury pain. J Neurotrauma 28:127-134, 2011
27. Hammer NA, Lillesø J, Pedersen JL, Kehlet H: Effect of riluzole on acute pain and hyperalgesia in humans. Br J Anaesth 82:718-722, 1999 (Pubitemid 29199746)
28. Hao JX, Xu XJ, Yu YX, Seiger A, Wiesenfeld-Hallin Z: Transient spinal cord ischemia induces temporary hypersensitivity of dorsal horn wide dynamic range neurons to myelinated, but not unmyelinated, fiber input. J Neurophysiol 68:384-391, 1992
29. Hargreaves K, Dubner R, Brown F, Flores C, Joris J: A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 32:77-88, 1988
30. Hogg-Johnson S, van der Velde G, Carroll LJ, Holm LW, Cassidy JD, Guzman J, et al: The burden and determinants of neck pain in the general population: results of the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders. Spine (Phila Pa 1976) 33 (4 Suppl):S39-S51, 2008
31. Hubbard RD, Chen Z, Winkelstein BA: Transient cervical nerve root compression modulates pain: load thresholds for allodynia and sustained changes in spinal neuropeptide expression. J Biomech 41:677-685, 2008 (Pubitemid 351179700)
32. Hubbard RD, Quinn KP, Martínez JJ, Winkelstein BA: The role of graded nerve root compression on axonal damage, neuropeptide changes, and pain-related behaviors. Stapp Car Crash J 52:33-58, 2008
33. Hubbard RD, Winkelstein BA: Dorsal root compression produces myelinated axonal degeneration near the biomechanical thresholds for mechanical behavioral hypersensitivity. Exp Neurol 212:482-489, 2008
34. Hubbard RD, Winkelstein BA: Transient cervical nerve root compression in the rat induces bilateral forepaw allodynia and spinal glial activation: mechanical factors in painful neck injuries. Spine (Phila Pa 1976) 30:1924-1932, 2005
35. Inquimbert P, Bartels K, Babaniyi OB, Barrett LB, Tegeder I, Scholz J: Peripheral nerve injury produces a sustained shift in the balance between glutamate release and uptake in the dorsal horn of the spinal cord. Pain 153:2422-2431, 2012
36. Jehle T, Bauer J, Blauth E, Hummel A, Darstein M, Freiman TM, et al: Effects of riluzole on electrically evoked neurotransmitter release. Br J Pharmacol 130:1227-1234, 2000 (Pubitemid 30488583)
37. Jensen TS, Gottrup H, Sindrup SH, Bach FW: The clinical picture of neuropathic pain. Eur J Pharmacol 429:1-11, 2001 (Pubitemid 33043977)
38. Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, et al: Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci 10:331-339, 2007
39. Kerr BJ, David S: Pain behaviors after spinal cord contusion injury in two commonly used mouse strains. Exp Neurol 206:240-247, 2007 (Pubitemid 47094766)
40. Kobayashi S, Kokubo Y, Uchida K, Yayama T, Takeno K, Negoro K, et al: Effect of lumbar nerve root compression on primary sensory neurons and their central branches: changes in the nociceptive neuropeptides substance P and somatostatin. Spine (Phila Pa 1976) 30:276-282, 2005
41. Kobayashi S, Uchida K, Kokubo Y, Takeno K, Yayama T, Miyazaki T, et al: Synapse involvement of the dorsal horn in experimental lumbar nerve root compression: a light and electron microscopic study. Spine (Phila Pa 1976) 33:716-723, 2008
42. Krenz NR, Weaver LC: Sprouting of primary afferent fibers after spinal cord transection in the rat. Neuroscience 85:443-458, 1998 (Pubitemid 28218665)
43. Krivickas LS, Wilbourn AJ: Peripheral nerve injuries in athletes: a case series of over 200 injuries. Semin Neurol 20:225-232, 2000 (Pubitemid 30483034)
44. Kwon BK, Okon E, Hillyer J, Mann C, Baptiste D, Weaver LC, et al: A systematic review of non-invasive pharmacologic neuroprotective treatments for acute spinal cord injury. J Neurotrauma 28:1545-1588, 2011
45. Laird JMA, Bennett GJ: An electrophysiological study of dorsal horn neurons in the spinal cord of rats with an experimental peripheral neuropathy. J Neurophysiol 69:2072-2085, 1993 (Pubitemid 23195673)
46. Le Liboux A, Cachia JP, Kirkesseli S, Gautier JY, Guimart C, Montay G, et al: A comparison of the pharmacokinetics and tolerability of riluzole after repeat dose administration in healthy elderly and young volunteers. J Clin Pharmacol 39:480-486, 1999 (Pubitemid 29356468)
47. Leinster VHL, Robson LG, Shortland PJ: Differential effects of riluzole on subpopulations of adult rat dorsal root ganglion neurons in vitro. Neuroscience 166:942-951, 2010
48. Liu FY, Qu XX, Cai J, Wang FT, Xing GG, Wan Y: Electrophysiological properties of spinal wide dynamic range neurons in neuropathic pain rats following spinal nerve ligation. Neurosci Bull 27:1-8, 2011
49. Mantz J, Chéramy A, Thierry AM, Glowinski J, Desmonts JM: Anesthetic properties of riluzole (54274 RP), a new inhibitor of glutamate neurotransmission. Anesthesiology 76:844-848, 1992
50. McMahon SB, Kett-White R: Sprouting of peripherally regenerating primary sensory neurones in the adult central nervous system. J Comp Neurol 304:307-315, 1991
51. Neugebauer V, Rümenapp P, Schaible HG: Calcitonin gene-related peptide is involved in the spinal processing of mechanosensory input from the rat's knee joint and in the generation and maintenance of hyperexcitability of dorsal horn-neurons during development of acute inflammation. Neuroscience 71:1095-1109, 1996
52. Nicholson KJ, Quindlen JC, Winkelstein BA: Development of a duration threshold for modulating evoked neuronal responses after nerve root compression injury. Stapp Car Crash J 55:1-24, 2011
53. Pedowitz RA, Garfin SR, Massie JB, Hargens AR, Swenson MR, Myers RR, et al: Effects of magnitude and duration of compression on spinal nerve root conduction. Spine (Phila Pa 1976) 17:194-199, 1992
54. Pintér S, Gloviczki B, Szabó A, Márton G, Nógrádi A: Increased survival and reinnervation of cervical motoneurons by riluzole after avulsion of the C7 ventral root. J Neurotrauma 27:2273-2282, 2010
55. Pitcher MH, Ribeiro-da-Silva A, Coderre TJ: Effects of inflammation on the ultrastructural localization of spinal cord dorsal horn group I metabotropic glutamate receptors. J Comp Neurol 505:412-423, 2007 (Pubitemid 350134062)
56. Quinn KP, Dong L, Golder FJ, Winkelstein BA: Neuronal hyperexcitability in the dorsal horn after painful facet joint injury. Pain 151:414-421, 2010
57. Ramer MS, Priestley JV, McMahon SB: Functional regeneration of sensory axons into the adult spinal cord. Nature 403:312-316, 2000 (Pubitemid 30062387)
58. Romero-Sandoval A, Chai N, Nutile-McMenemy N, Deleo JA: A comparison of spinal Iba1 and GFAP expression in rodent models of acute and chronic pain. Brain Res 1219:116-126, 2008
59. Rothman SM, Kreider RA, Winkelstein BA: Spinal neuropeptide responses in persistent and transient pain following cervical nerve root injury. Spine (Phila Pa 1976) 30:2491-2496, 2005
60. Rothman SM, Nicholson KJ, Winkelstein BA: Time-dependent mechanics and measures of glial activation and behavioral sensitivity in a rodent model of radiculopathy. J Neurotrauma 27:803-814, 2010
61. Saito K, Hitomi S, Suzuki I, Masuda Y, Kitagawa J, Tsuboi Y, et al: Modulation of trigeminal spinal subnucleus caudalis neuronal activity following regeneration of transected inferior alveolar nerve in rats. J Neurophysiol 99:2251-2263, 2008
62. Schwartz G, Fehlings MG: Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole. J Neurosurg 94 (2 Suppl):245-256, 2001 (Pubitemid 32786052)
63. Serbest G, Burkhardt MF, Siman R, Raghupathi R, Saatman KE: Temporal profiles of cytoskeletal protein loss following traumatic axonal injury in mice. Neurochem Res 32:2006-2014, 2007 (Pubitemid 350059844)
64. Shim B, Kim DW, Kim BH, Nam TS, Leem JW, Chung JM: Mechanical and heat sensitization of cutaneous nociceptors in rats with experimental peripheral neuropathy. Neuroscience 132:193-201, 2005 (Pubitemid 40380726)
65. Shortland PJ, Leinster VHL, White W, Robson LG: Riluzole promotes cell survival and neurite outgrowth in rat sensory neurones in vitro. Eur J Neurosci 24:3343-3353, 2006 (Pubitemid 44952600)
66. Singh A, Lu Y, Chen C, Kallakuri S, Cavanaugh JM: A new model of traumatic axonal injury to determine the effects of strain and displacement rates. Stapp Car Crash J 50:601-623, 2006
67. Siniscalchi A, Bonci A, Mercuri NB, Bernardi G: Effects of riluzole on rat cortical neurones: an in vitro electrophysiological study. Br J Pharmacol 120:225-230, 1997 (Pubitemid 27039271)
68. Stutzmann JM, Pratt J, Boraud T, Gross C: The effect of riluzole on post-traumatic spinal cord injury in the rat. Neuroreport 7:387-392, 1996 (Pubitemid 26105006)
69. Sung B, Lim G, Mao J: Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J Neurosci 23:2899-2910, 2003 (Pubitemid 36418626)
70. Tao YX, Gu J, Stephens RL Jr: Role of spinal cord glutamate transporter during normal sensory transmission and pathological pain states. Mol Pain 1:30, 2005
71. Terashima Y, Kawamata M, Takebayashi T, Tanaka S, Tanimoto K, Yamashita T: Changes in synaptic transmission of substantia gelatinosa neurons in a rat model of lumbar radicular pain revealed by in vivo patch-clamp recording. Pain 152:1024-1032, 2011
72. Urch CE, Dickenson AH: In vivo extracellular recordings from spinal cord neurons of rats. Brain Res Brain Res Protoc 12:26-34, 2003 (Pubitemid 36962991)
73. Vorwerk CK, Zurakowski D, McDermott LM, Mawrin C, Dreyer EB: Effects of axonal injury on ganglion cell survival and glutamate homeostasis. Brain Res Bull 62:485-490, 2004 (Pubitemid 38253033)
74. Wainner RS, Gill H: Diagnosis and nonoperative management of cervical radiculopathy. J Orthop Sports Phys Ther 30:728-744, 2000 (Pubitemid 32011872)
75. Woolf CJ, Fitzgerald M: The properties of neurones recorded in the superficial dorsal horn of the rat spinal cord. J Comp Neurol 221:313-328, 1983 (Pubitemid 14216763)
76. Wu Y, Satkunendrarajah K, Teng Y, Chow DSL, Buttigieg J, Fehlings MG: Delayed post-injury administration of riluzole is neuroprotective in a preclinical rodent model of cervical spinal cord injury. J Neurotrauma 30:441-452, 2013
77. Yang Y, Gozen O, Watkins A, Lorenzini I, Lepore A, Gao Y, et al: Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron 61:880-894, 2009
78. Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16:109-110, 1983