Mechanisms of the gabapentinoids and α2δ-1 calcium channel subunit in neuropathic pain

Pharmacology Research and Perspectives

Volumn 4, Issue 2, 2016, Pages

  Patel, Ryan ^a   Dickenson, Anthony H ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

Author keywords

Alpha 2 delta 1; calcium channel subunit; gabapentin; neuropathic pain; pregabalin

Indexed keywords

ALPHA2 DELTA1 CALCIUM CHANNEL SUBUNIT; ANALGESIC AGENT; CALCIUM CHANNEL; GABAPENTIN; GABAPENTINOID; PREGABALIN; UNCLASSIFIED DRUG;

ANALGESIC ACTIVITY; CALCIUM SIGNALING; HUMAN; HYPERALGESIA; INFLAMMATION; NEUROPATHIC PAIN; NEUROTRANSMISSION; NOCICEPTIVE STIMULATION; NONHUMAN; PAIN THRESHOLD; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; ROSTRAL VENTROMEDIAL MEDULLA; SYNAPSE; TEMPORAL SUMMATION;

EID: 84995532799     PISSN: None     EISSN: 20521707     Source Type: Journal    
DOI: 10.1002/prp2.205     Document Type: Review

References (107)

1. Arendt-Nielsen L, Frokjaer JB, Staahl C, Graven-Nielsen T, Huggins JP, Smart TS, et al. (2007). Effects of gabapentin on experimental somatic pain and temporal summation. Reg Anesth Pain Med 32: 382–388.
2. Arikkath J, Campbell KP (2003). Auxiliary subunits: essential components of the voltage-gated calcium channel complex. Curr Opin Neurobiol 13: 298–307.
3. Attal N, Brasseur L, Parker F, Chauvin M, Bouhassira D (1998). Effects of gabapentin on the different components of peripheral and central neuropathic pain syndromes: a pilot study. Eur Neurol 40: 191–200.
4. Bannister JP, Adebiyi A, Zhao G, Narayanan D, Thomas CM, Feng JY, et al. (2009). Smooth muscle cell alpha2delta-1 subunits are essential for vasoregulation by CaV1.2 channels. Circ Res 105: 948–955.
5. Bannister K, Sikandar S, Bauer CS, Dolphin AC, Porreca F, Dickenson AH (2011). Pregabalin suppresses spinal neuronal hyperexcitability and visceral hypersensitivity in the absence of peripheral pathophysiology. Anesthesiology 115: 144–152.
6. Bannister K, Patel R, Goncalves L, Townson L, Dickenson AH (2015). Diffuse noxious inhibitory controls and nerve injury: restoring an imbalance between descending monoamine inhibitions and facilitations. Pain 156: 1803–1811.
7. Bauer CS, Nieto-Rostro M, Rahman W, Tran-Van-Minh A, Ferron L, Douglas L, et al. (2009). The increased trafficking of the calcium channel subunit alpha2delta-1 to presynaptic terminals in neuropathic pain is inhibited by the alpha2delta ligand pregabalin. J Neurosci 29: 4076–4088.
8. Bee LA, Dickenson AH (2008). Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin. Pain 140: 209–223.
9. Bernstein GM, Jones OT (2007). Kinetics of internalization and degradation of N-type voltage-gated calcium channels: role of the alpha2/delta subunit. Cell Calcium 41: 27–40.
10. Berry JD, Petersen KL (2005). A single dose of gabapentin reduces acute pain and allodynia in patients with herpes zoster. Neurology 65: 444–447.
11. Boroujerdi A, Kim HK, Lyu YS, Kim DS, Figueroa KW, Chung JM, et al. (2008). Injury discharges regulate calcium channel alpha-2-delta-1 subunit upregulation in the dorsal horn that contributes to initiation of neuropathic pain. Pain 139: 358–366.
12. Brown JT, Randall A (2005). Gabapentin fails to alter P/Q-type Ca2+ channel-mediated synaptic transmission in the hippocampus in vitro. Synapse (New York, N.Y.), 55: 262–269.
13. Canti C, Nieto-Rostro M, Foucault I, Heblich F, Wratten J, Richards MW, et al. (2005). The metal-ion-dependent adhesion site in the Von Willebrand factor-A domain of alpha2delta subunits is key to trafficking voltage-gated Ca2 + channels. Proc Natl Acad Sci USA 102: 11230–11235.
14. Cassidy JS, Ferron L, Kadurin I, Pratt WS, Dolphin AC (2014). Functional exofacially tagged N-type calcium channels elucidate the interaction with auxiliary α2δ-1 subunits. Proc Natl Acad Sci USA 111: 8979–8984.
15. Chang EY, Chen X, Sandhu A, Li CY, Luo ZD (2013). Spinal 5-HT3 receptors facilitate behavioural hypersensitivity induced by elevated calcium channel alpha-2-delta-1 protein. Euro J Pain (London, England), 17, 505–513.
16. Chang E, Chen X, Kim M, Gong N, Bhatia S, Luo ZD (2015) Differential effects of voltage-gated calcium channel blockers on calcium channel alpha-2-delta-1 subunit protein-mediated nociception. Euro J Pain (London, England) 19: 639–648.
17. Chizh BA, Gohring M, Troster A, Quartey GK, Schmelz M, Koppert W (2007). Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers. Br J Anaesth 98: 246–254.
18. Cole RL, Lechner SM, Williams ME, Prodanovich P, Bleicher L, Varney MA, et al. (2005). Differential distribution of voltage-gated calcium channel alpha-2 delta (alpha2delta) subunit mRNA-containing cells in the rat central nervous system and the dorsal root ganglia. J Comp Neurol 491: 246–269.
19. Costigan M, Befort K, Karchewski L, Griffin RS, D'Urso D, Allchorne A, et al. (2002). Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neurosci 3: 16.
20. D'Arco M, Margas W, Cassidy JS, Dolphin AC (2015). The upregulation of alpha2delta-1 subunit modulates activity-dependent Ca2+ signals in sensory neurons. J Neurosci 35: 5891–5903.
21. Davies A, Douglas L, Hendrich J, Wratten J, Tran Van Minh A, Foucault I, et al. (2006). The calcium channel alpha2delta-2 subunit partitions with CaV2.1 into lipid rafts in cerebellum: implications for localization and function. J Neurosci 26: 8748–8757.
22. Davies A, Kadurin I, Alvarez-Laviada A, Douglas L, Nieto-Rostro M, Bauer CS, et al. (2010). The alpha2delta subunits of voltage-gated calcium channels form GPI-anchored proteins, a posttranslational modification essential for function. Proc Natl Acad Sci USA 107: 1654–1659.
23. De Jongh KS, Warner C, Catterall WA (1990). Subunits of purified calcium channels. Alpha 2 and delta are encoded by the same gene. J Biol Chem 265: 14738–14741.
24. De Waard M, Campbell KP (1995). Subunit regulation of the neuronal alpha 1A Ca2+ channel expressed in Xenopus oocytes. J Physiol 485: 619–634.
25. Dirks J, Petersen KL, Rowbotham MC, Dahl JB (2002). Gabapentin suppresses cutaneous hyperalgesia following heat-capsaicin sensitization. Anesthesiology 97: 102–107.
26. Dolphin AC (2013). The alpha2delta subunits of voltage-gated calcium channels. Biochim Biophys Acta 1828: 1541–1549.
27. Donovan-Rodriguez T, Dickenson AH, Urch CE (2005). Gabapentin normalizes spinal neuronal responses that correlate with behavior in a rat model of cancer-induced bone pain. Anesthesiology 102: 132–140.
28. Dworkin RH, Corbin AE, Young JP Jr, Sharma U, LaMoreaux L, Bockbrader H, et al. (2003). Pregabalin for the treatment of postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 60: 1274–1283.
29. Eroglu C, Allen NJ, Susman MW, O'Rourke NA, Park CY, Ozkan E, et al. (2009). Gabapentin receptor alpha2delta-1 is a neuronal thrombospondin receptor responsible for excitatory CNS synaptogenesis. Cell 139: 380–392.
30. Fehrenbacher JC, Taylor CP, Vasko MR (2003). Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain 105: 133–141.
31. Felix R, Gurnett CA, De Waard M, Campbell KP (1997). Dissection of functional domains of the voltage-dependent Ca2+ channel alpha2delta subunit. J Neurosci 17: 6884–6891.
32. Feltner DE, Crockatt JG, Dubovsky SJ, Cohn CK, Shrivastava RK, Targum SD, et al. (2003). A randomized, double-blind, placebo-controlled, fixed-dose, multicenter study of pregabalin in patients with generalized anxiety disorder. J Clin Psychopharmacol 23: 240–249.
33. Field MJ, Oles RJ, Lewis AS, McCleary S, Hughes J, Singh L (1997). Gabapentin (neurontin) and S-(+)-3-isobutylgaba represent a novel class of selective antihyperalgesic agents. Br J Pharmacol 121: 1513–1522.
34. Field MJ, Cox PJ, Stott E, Melrose H, Offord J, Su T-Z, et al. (2006). Identification of the α2-δ-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci USA 103: 17537–17542.
35. Fink K, Meder W, Dooley DJ, Gothert M (2000). Inhibition of neuronal Ca(2+) influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices. Br J Pharmacol 130: 900–906.
36. Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. (2015). Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14: 162–173.
37. Freeman R, Baron R, Bouhassira D, Cabrera J, Emir B (2014). Sensory profiles of patients with neuropathic pain based on the neuropathic pain symptoms and signs. Pain 155: 367–376.
38. Fuller-Bicer GA, Varadi G, Koch SE, Ishii M, Bodi I, Kadeer N, et al. (2009). Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit. Am J Physiol Heart Circ Physiol 297: H117–H124.
39. Gach MP, Cherednichenko G, Haarmann C, Lopez JR, Beam KG, Pessah IN, et al. (2008). Alpha2delta1 dihydropyridine receptor subunit is a critical element for excitation-coupled calcium entry but not for formation of tetrads in skeletal myotubes. Biophys J 94: 3023–3034.
40. Garcia K, Nabhani T, Garcia J (2008). The calcium channel alpha2/delta1 subunit is involved in extracellular signalling. J Physiol 586: 727–738.
41. Gee NS, Brown JP, Dissanayake VU, Offord J, Thurlow R, Woodruff GN (1996). The novel anticonvulsant drug, gabapentin (Neurontin), binds to the alpha2delta subunit of a calcium channel. J Biol Chem 271: 5768–5776.
42. Goncalves L, Dickenson AH (2012). Asymmetric time-dependent activation of right central amygdala neurones in rats with peripheral neuropathy and pregabalin modulation. Eur J Neuorsci 36: 3204–3213.
43. Gottrup H, Juhl G, Kristensen AD, Lai R, Chizh BA, Brown J, et al. (2004). Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgesia. Anesthesiology 101: 1400–1408.
44. Griggs RB, Bardo MT, Taylor BK (2015). Gabapentin alleviates affective pain after traumatic nerve injury. NeuroReport 26: 522–527.
45. Hara K, Sata T (2007). Inhibitory effect of gabapentin on N-methyl-D-aspartate receptors expressed in Xenopus oocytes. Acta Anaesthesiol Scand 51: 122–128.
46. Hayashida K, DeGoes S, Curry R, Eisenach JC (2007). Gabapentin activates spinal noradrenergic activity in rats and humans and reduces hypersensitivity after surgery. Anesthesiology 106: 557–562.
47. Hendrich J, Van Minh AT, Heblich F, Nieto-Rostro M, Watschinger K, Striessnig J, et al. (2008). Pharmacological disruption of calcium channel trafficking by the alpha2delta ligand gabapentin. Proc Natl Acad Sci USA 105: 3628–3633.
48. Hobom M, Dai S, Marais E, Lacinova L, Hofmann F, Klugbauer N (2000). Neuronal distribution and functional characterization of the calcium channel alpha2delta-2 subunit. Eur J Neuorsci 12: 1217–1226.
49. Hoppa MB, Lana B, Margas W, Dolphin AC, Ryan TA (2012). α2δ expression sets presynaptic calcium channel abundance and release probability. Nature 486: 122–125.
50. Hua XY, Chen P, Yaksh TL (1999). Inhibition of spinal protein kinase C reduces nerve injury-induced tactile allodynia in neuropathic rats. Neurosci Lett 276: 99–102.
51. Hunter JC, Gogas KR, Hedley LR, Jacobson LO, Kassotakis L, Thompson J, et al. (1997). The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol 324: 153–160.
52. Iannetti GD, Zambreanu L, Wise RG, Buchanan TJ, Huggins JP, Smart TS, et al. (2005). Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans. Proc Natl Acad Sci USA 102: 18195–18200.
53. Jensen AA, Mosbacher J, Elg S, Lingenhoehl K, Lohmann T, Johansen TN, et al. (2002). The anticonvulsant gabapentin (Neurontin) does not act through γ-aminobutyric acid-B receptors. Mol Pharmacol 61: 1377–1384.
54. Kim JS, Bashford G, Murphy TK, Martin A, Dror V, Cheung R (2011). Safety and efficacy of pregabalin in patients with central post-stroke pain. Pain 152: 1018–1023.
55. Kim YS, Chu Y, Han L, Li M, Li Z, Lavinka PC, et al. (2014). Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain. Neuron 81: 873–887.
56. Klugbauer N, Lacinova L, Marais E, Hobom M, Hofmann F (1999). Molecular diversity of the calcium channel alpha2delta subunit. J Neurosci 19: 684–691.
57. Koppert W, Dern SK, Sittl R, Albrecht S, Schuttler J, Schmelz M (2001). A new model of electrically evoked pain and hyperalgesia in human skin: the effects of intravenous alfentanil, S(+)-ketamine, and lidocaine. Anesthesiology 95: 395–402.
58. Kusunose N, Koyanagi S, Hamamura K, Matsunaga N, Yoshida M, Uchida T, et al. (2010). Molecular basis for the dosing time-dependency of anti-allodynic effects of gabapentin in a mouse model of neuropathic pain. Mol Pain 6: 83.
59. Lana B, Schlick B, Martin S, Pratt WS, Page KM, Goncalves L, et al. (2014). Differential upregulation in DRG neurons of an alpha2delta-1 splice variant with a lower affinity for gabapentin after peripheral sensory nerve injury. Pain 155: 522–533.
60. Lanneau C, Green A, Hirst WD, Wise A, Brown JT, Donnier E, et al. (2001). Gabapentin is not a GABA B receptor agonist. Neuropharmacology 41: 965–975.
61. Li CY, Song YH, Higuera ES, Luo ZD (2004). Spinal dorsal horn calcium channel alpha2delta-1 subunit upregulation contributes to peripheral nerve injury-induced tactile allodynia. J Neurosci 24: 8494–8499.
62. Li CY, Zhang XL, Matthews EA, Li KW, Kurwa A, Boroujerdi A, et al. (2006). Calcium channel alpha2delta1 subunit mediates spinal hyperexcitability in pain modulation. Pain 125: 20–34.
63. Lotarski SM, Donevan S, El-Kattan A, Osgood S, Poe J, Taylor CP, et al. (2011). Anxiolytic-like activity of pregabalin in the Vogel conflict test in alpha2delta-1 (R217A) and alpha2delta-2 (R279A) mouse mutants. J Pharmacol Exp Therapeut 338: 615–621.
64. Luo ZD, Chaplan SR, Higuera ES, Sorkin LS, Stauderman KA, Williams ME, et al. (2001). Upregulation of dorsal root ganglion α2δ calcium channel subunit and its correlation with allodynia in spinal nerve-injured rats. J Neurosci 21: 1868–1875.
65. Maneuf YP, McKnight AT (2001). Block by gabapentin of the facilitation of glutamate release from rat trigeminal nucleus following activation of protein kinase C or adenylyl cyclase. Br J Pharmacol 134: 237–240.
66. Marais E, Klugbauer N, Hofmann F (2001). Calcium channel alpha(2)delta subunits-structure and Gabapentin binding. Mol Pharmacol 59: 1243–1248.
67. Mellick GA, Mellicy LB, Mellick LB (1995). Gabapentin in the management of reflex sympathetic dystrophy. J Pain Symptom Manage 10: 265–266.
68. Mich PM, Horne WA (2008). Alternative splicing of the Ca2 + channel beta4 subunit confers specificity for gabapentin inhibition of Cav2.1 trafficking. Mol Pharmacol 74: 904–912.
69. Miyazaki R, Yamamoto T (2012). The efficacy of morphine, pregabalin, gabapentin, and duloxetine on mechanical allodynia is different from that on neuroma pain in the rat neuropathic pain model. Anest Analg 115: 182–188.
70. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ (2009) Pregabalin for acute and chronic pain in adults. Cochrane Database Syst Rev, Cd007076.
71. Moore RA, Wiffen PJ, Derry S, Toelle T, Rice AS (2014). Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database Syst Rev 4, Cd007938.
72. Nasca C, Orlando R, Marchiafava M, Boldrini P, Battaglia G, Scaccianoce S, et al. (2013). Exposure to predator odor and resulting anxiety enhances the expression of the alpha2 delta subunit of voltage-sensitive calcium channels in the amygdala. J Neurochem 125: 649–656.
73. Nguyen D, Deng P, Matthews EA, Kim DS, Feng G, Dickenson AH, et al. (2009). Enhanced pre-synaptic glutamate release in deep-dorsal horn contributes to calcium channel alpha-2-delta-1 protein-mediated spinal sensitization and behavioral hypersensitivity. Mol Pain 5: 6.
74. Niesters M, Proto PL, Aarts L, Sarton EY, Drewes AM, Dahan A (2014). Tapentadol potentiates descending pain inhibition in chronic pain patients with diabetic polyneuropathy. Br J Anaesth 113: 148–156.
75. Ohtori S, Inoue G, Orita S, Takaso M, Eguchi Y, Ochiai N, et al. (2013). Efficacy of combination of meloxicam and pregabalin for pain in knee osteoarthritis. Yonsei Med J 54: 1253–1258.
76. Olesen SS, Graversen C, Bouwense SA, van Goor H, Wilder-Smith OH, Drewes AM (2013). Quantitative sensory testing predicts pregabalin efficacy in painful chronic pancreatitis. PLoS One 8: e57963.
77. O'Neill J, Brock C, Olesen AE, Andresen T, Nilsson M, Dickenson AH (2012). Unravelling the mystery of capsaicin: a tool to understand and treat pain. Pharmacol Rev 64: 939–971.
78. Patel R, Bauer CS, Nieto-Rostro M, Margas W, Ferron L, Chaggar K, et al. (2013). α2δ-1 Gene deletion affects somatosensory neuron function and delays mechanical hypersensitivity in response to peripheral nerve damage. J Neurosci 33: 16412–16426.
79. Quintero JE, Dooley DJ, Pomerleau F, Huettl P, Gerhardt GA (2011). Amperometric measurement of glutamate release modulation by gabapentin and pregabalin in rat neocortical slices: role of voltage-sensitive Ca2 + alpha2delta-1 subunit. J Pharmacol Exp Therap 338: 240–245.
80. Rahman W, Bauer CS, Bannister K, Vonsy JL, Dolphin AC, Dickenson AH (2009). Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain. Mol Pain 5: 45.
81. Schmidt PC, Ruchelli G, Mackey SC, Carroll IR (2013). Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain. Anesthesiology 119: 1215–1221.
82. Segerdahl M (2006). Multiple dose gabapentin attenuates cutaneous pain and central sensitisation but not muscle pain in healthy volunteers. Pain 125: 158–164.
83. van Seventer R, Bach FW, Toth CC, Serpell M, Temple J, Murphy TK, et al. (2010). Pregabalin in the treatment of post-traumatic peripheral neuropathic pain: a randomized double-blind trial. Eur J Neurol 17: 1082–1089.
84. Shimoyama N, Shimoyama M, Davis AM, Inturrisi CE, Elliott KJ (1997). Spinal gabapentin is antinociceptive in the rat formalin test. Neurosci Lett 222: 65–67.
85. Sikandar S, Dickenson AH (2011). Pregabalin modulation of spinal and brainstem visceral nociceptive processing. Pain 152: 2312–2322.
86. Sikandar S, Bannister K, Dickenson AH (2012). Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats. Neurosci Lett 519: 31–36.
87. Simpson DM, Schifitto G, Clifford DB, Murphy TK, Durso-De Cruz E, Glue P, et al. (2010). Pregabalin for painful HIV neuropathy: a randomized, double-blind, placebo-controlled trial. Neurology 74: 413–420.
88. Stanfa LC, Singh L, Williams RG, Dickenson AH (1997). Gabapentin, ineffective in normal rats, markedly reduces C-fibre evoked responses after inflammation. NeuroReport 8: 587–590.
89. Stefani A, Spadoni F, Bernardi G (1998). Gabapentin inhibits calcium currents in isolated rat brain neurons. Neuropharmacology 37: 83–91.
90. Sutton KG, Martin DJ, Pinnock RD, Lee K, Scott RH (2002). Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol 135: 257–265.
91. Suzuki R, Dickenson AH (2006). Differential pharmacological modulation of the spontaneous stimulus-independent activity in the rat spinal cord following peripheral nerve injury. Exp Neurol 198: 72–80.
92. Suzuki R, Rahman W, Hunt SP, Dickenson AH (2004). Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury. Brain Res 1019: 68–76.
93. Suzuki R, Rahman W, Rygh LJ, Webber M, Hunt SP, Dickenson AH (2005). Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. Pain 117: 292–303.
94. Takasu K, Ono H, Tanabe M (2008). Gabapentin produces PKA-dependent pre-synaptic inhibition of GABAergic synaptic transmission in LC neurons following partial nerve injury in mice. J Neurochem 105: 933–942.
95. Takeuchi Y, Takasu K, Ono H, Tanabe M (2007). Pregabalin, S-(+)-3-isobutylgaba, activates the descending noradrenergic system to alleviate neuropathic pain in the mouse partial sciatic nerve ligation model. Neuropharmacology 53: 842–853.
96. Tanabe M, Takasu K, Kasuya N, Shimizu S, Honda M, Ono H (2005). Role of descending noradrenergic system and spinal alpha2-adrenergic receptors in the effects of gabapentin on thermal and mechanical nociception after partial nerve injury in the mouse. Br J Pharmacol 144: 703–714.
97. Taylor CP, Garrido R (2008). Immunostaining of rat brain, spinal cord, sensory neurons and skeletal muscle for calcium channel alpha2-delta (alpha2-delta) type 1 protein. Neuroscience 155: 510–521.
98. Thakur M, Rahman W, Hobbs C, Dickenson AH, Bennett DL (2012). Characterization of a peripheral neuropathic component of the rat monoiodoacetate model of osteoarthritis. PLoS One 7: e33730.
99. Thakur M, Dickenson AH, Baron R (2014). Osteoarthritis pain: nociceptive or neuropathic?. Nat Rev Rheumatol 10: 374–380.
100. Tran-Van-Minh A, Dolphin AC (2010). The alpha2delta ligand gabapentin inhibits the Rab11-dependent recycling of the calcium channel subunit alpha2delta-2. J Neurosci 30: 12856–12867.
101. Wang H, Sun H, Della Penna K, Benz R, Xu J, Gerhold D, et al. (2002). Chronic neuropathic pain is accompanied by global changes in gene expression and shares pathobiology with neurodegenerative diseases. Neuroscience 114: 529–546.
102. Werner MU, Perkins FM, Holte K, Pedersen JL, Kehlet H (2001). Effects of gabapentin in acute inflammatory pain in humans. Reg Anesth Pain Med 26: 322–328.
103. Wiffen PJ, Derry S, Moore RA, Aldington D, Cole P, Rice AS, et al. (2013). Antiepileptic drugs for neuropathic pain and fibromyalgia – an overview of Cochrane reviews. Cochrane Database Syst Rev, 11, Cd010567.
104. Xiao HS, Huang QH, Zhang FX, Bao L, Lu YJ, Guo C, et al. (2002). Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proc Natl Acad Sci USA 99: 8360–8365.
105. Yang RH, Wang WT, Chen JY, Xie RG, Hu SJ (2009). Gabapentin selectively reduces persistent sodium current in injured type-A dorsal root ganglion neurons. Pain 143: 48–55.
106. Yarnitsky D, Granot M, Nahman-Averbuch H, Khamaisi M, Granovsky Y (2012). Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain 153: 1193–1198.
107. Zhou C, Luo ZD (2014). Electrophysiological characterization of spinal neuron sensitization by elevated calcium channel alpha-2-delta-1 subunit protein. Europ J Pain (London, England) 18: 649–658.