Therapeutic use of botulinum toxin in migraine: Mechanisms of action

British Journal of Pharmacology

Volumn 171, Issue 18, 2014, Pages 4177-4192

  Ramachandran, Roshni ^a   Yaksh, Tony L ^a  

^a University of California at San Diego   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BOTULINUM TOXIN; SNARE PROTEIN;

ANIMAL; HUMAN; METABOLISM; MIGRAINE DISORDERS; PAIN; SENSORY NERVE CELL;

ANIMALS; BOTULINUM TOXINS; HUMANS; MIGRAINE DISORDERS; NEURONS, AFFERENT; PAIN; SNARE PROTEINS;

EID: 84906836383     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.12763     Document Type: Review

References (203)

1. Acquadro MA, Borodic GE, (1994). Treatment of myofascial pain with botulinum A toxin. Anesthesiology 80: 705-706.
2. Ahmad M, Polepalli JS, Goswami D, Yang X, Kaeser-Woo YJ, Sudhof TC, et al. (2012). Postsynaptic complexin controls AMPA receptor exocytosis during LTP. Neuron 73: 260-267.
3. Akaike N, Shin MC, Wakita M, Torii Y, Harakawa T, Ginnaga A, et al. (2013). Transsynaptic inhibition of spinal transmission by A2 botulinum toxin. J Physiol 591: 1031-1043.
4. Akerman S, Kaube H, Goadsby PJ, (2003). Vanilloid type 1 receptors (VR1) on trigeminal sensory nerve fibres play a minor role in neurogenic dural vasodilatation, and are involved in capsaicin-induced dural dilation. Br J Pharmacol 140: 718-724.
5. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Catterall WA, et al. (2013a). The Concise Guide to PHARMACOLOGY 2013/14: Ligand-Gated Ion Channels. Br J Pharmacol 170: 1582-1606.
6. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. (2013b). The Concise Guide to PHARMACOLOGY 2013/14: G Protein-Coupled Receptors. Br J Pharmacol 170: 1459-1581
7. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Catterall WA, et al. (2013c). The Concise Guide to PHARMACOLOGY 2013/14: Ion Channels. Br J Pharmacol 170: 1607-1651.
8. Anand KS, Prasad A, Singh MM, Sharma S, Bala K, (2006). Botulinum toxin type A in prophylactic treatment of migraine. Am J Ther 13: 183-187.
9. Angers CG, Merz AJ, (2011). New links between vesicle coats and Rab-mediated vesicle targeting. Semin Cell Dev Biol 22: 18-26.
10. Antonucci F, Rossi C, Gianfranceschi L, Rossetto O, Caleo M, (2008). Long-distance retrograde effects of botulinum neurotoxin A. J Neurosci 28: 3689-3696.
11. Aoki KR, (2003). Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache 43 (Suppl. 1): S9-S15.
12. Aoki KR, (2005). Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A. Neurotoxicology 26: 785-793.
13. Aurora SK, Dodick DW, Turkel CC, DeGryse RE, Silberstein SD, Lipton RB, et al. (2010). OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 1 trial. Cephalalgia 30: 793-803.
14. Aurora SK, Winner P, Freeman MC, Spierings EL, Heiring JO, DeGryse RE, et al. (2011). Onabotulinumtoxin A for treatment of chronic migraine: pooled analyses of the 56-week PREEMPT clinical program. Headache 51: 1358-1373.
15. Bach-Rojecky L, Lackovic Z, (2005). Antinociceptive effect of botulinum toxin type a in rat model of carrageenan and capsaicin induced pain. Croat Med J 46: 201-208.
16. Bach-Rojecky L, Lackovic Z, (2009). Central origin of the antinociceptive action of botulinum toxin type A. Pharmacol Biochem Behav 94: 234-238.
17. Bach-Rojecky L, Dominis M, Lackovic Z, (2008). Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation. Fundam Clin Pharmacol 22: 503-509.
18. Barrientos N, Chana P, (2003). Botulinum toxin type A in prophylactic treatment of migraine headaches: a preliminary study. J Headache Pain 4: 146-151.
19. Bartsch T, Goadsby PJ, (2003). The trigeminocervical complex and migraine: current concepts and synthesis. Curr Pain Headache Rep 7: 371-376.
20. Binder WJ, Blitzer A, Brin MF, (1998). Treatment of hyperfunctional lines of the face with botulinum toxin A. Dermatol Surg 24: 1198-1205.
21. Black JD, Dolly JO, (1986). Interaction of 125I-labeled botulinum neurotoxins with nerve terminals. I. Ultrastructural autoradiographic localization and quantitation of distinct membrane acceptors for types A and B on motor nerves. J Cell Biol 103: 521-534.
22. Blumenfeld AM, Schim JD, Chippendale TJ, (2008). Botulinum toxin type A and divalproex sodium for prophylactic treatment of episodic or chronic migraine. Headache 48: 210-220.
23. Borodic GE, Acquadro M, Johnson EA, (2001). Botulinum toxin therapy for pain and inflammatory disorders: mechanisms and therapeutic effects. Expert Opin Investig Drugs 10: 1531-1544.
24. Bottinger H, Reuner KH, Aktories K, (1987). Inhibition of histamine release from rat mast cells by botulinum C2 toxin. Int Arch Allergy Appl Immunol 84: 380-384.
25. Bove GM, Moskowitz MA, (1997). Primary afferent neurons innervating guinea pig dura. J Neurophysiol 77: 299-308.
26. Brain SD, Grant AD, (2004). Vascular actions of calcitonin gene-related peptide and adrenomedullin. Physiol Rev 84: 903-934.
27. Brin MF, Fahn S, Moskowitz C, Friedman A, Shale HM, Greene PE, et al. (1987). Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Mov Disord 2: 237-254.
28. Brumovsky PR, Gebhart GF, (2010). Visceral organ cross-sensitization-an integrated perspective. Auton Neurosci 153: 106-115.
29. Burstein R, Jakubowski M, (2004). Analgesic triptan action in an animal model of intracranial pain: a race against the development of central sensitization. Ann Neurol 55: 27-36.
30. Burstein R, Yamamura H, Malick A, Strassman AM, (1998). Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J Neurophysiol 79: 964-982.
31. Burstein R, Cutrer MF, Yarnitsky D, (2000a). The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain 123 (Pt 8): 1703-1709.
32. Burstein R, Cutrer MF, Yarnitsky D, (2000b). The development of cutaneous allodynia during a migraine attack clinical evidence for the sequential recruitment of spinal and supraspinal nociceptive neurons in migraine. Brain 123 (Pt 8): 1703-1709.
33. Burstein R, Collins B, Jakubowski M, (2004). Defeating migraine pain with triptans: a race against the development of cutaneous allodynia. Ann Neurol 55: 19-26.
34. Burstein R, Zhang X, Levy D, Aoki KR, Brin MF, (2014). Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: therapeutic implications for migraine and other pains. Cephalalgia. doi: 10.1177/0333102414527648.
35. Buzzi MG, Carter WB, Shimizu T, Heath H III, Moskowitz MA, (1991). Dihydroergotamine and sumatriptan attenuate levels of CGRP in plasma in rat superior sagittal sinus during electrical stimulation of the trigeminal ganglion. Neuropharmacology 30: 1193-1200.
36. clinicaltrials.gov (2014). Use of SB-705498 in the acute treatment of migraine. http://clinicaltrials.gov/ct2/show/study/NCT00269022
37. Cady RK, Schreiber CP, Porter JA, Blumenfeld AM, Farmer KU, (2011). A multi-center double-blind pilot comparison of onabotulinumtoxinA and topiramate for the prophylactic treatment of chronic migraine. Headache 51: 21-32.
38. Carmichael NM, Dostrovsky JO, Charlton MP, (2010). Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin. Pain 149: 316-324.
39. Chamberlain LH, Burgoyne RD, Gould GW, (2001). SNARE proteins are highly enriched in lipid rafts in PC12 cells: implications for the spatial control of exocytosis. Proc Natl Acad Sci U S A 98: 5619-5624.
40. Chankrachang S, Arayawichanont A, Poungvarin N, Nidhinandana S, Boonkongchuen P, Towanabut S, et al. (2011). Prophylactic botulinum type A toxin complex (Dysport®) for migraine without aura. Headache 51: 52-63.
41. Cheshire WP, Abashian SW, Mann JD, (1994). Botulinum toxin in the treatment of myofascial pain syndrome. Pain 59: 65-69.
42. Chinnapongse RB, Lew MF, Ferreira JJ, Gullo KL, Nemeth PR, Zhang Y, (2012). Immunogenicity and long-term efficacy of botulinum toxin type B in the treatment of cervical dystonia: report of 4 prospective, multicenter trials. Clin Neuropharmacol 35: 215-223.
43. Choi JI, Svensson CI, Koehrn FJ, Bhuskute A, Sorkin LS, (2010). Peripheral inflammation induces tumor necrosis factor dependent AMPA receptor trafficking and Akt phosphorylation in spinal cord in addition to pain behavior. Pain 149: 243-253.
44. Cui M, Khanijou S, Rubino J, Aoki KR, (2004). Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain 107: 125-133.
45. Diener HC, Dodick DW, Aurora SK, Turkel CC, DeGryse RE, Lipton RB, et al. (2010). OnabotulinumtoxinA for treatment of chronic migraine: results from the double-blind, randomized, placebo-controlled phase of the PREEMPT 2 trial. Cephalalgia 30: 804-814.
46. Dimitriadou V, Buzzi MG, Moskowitz MA, Theoharides TC, (1991). Trigeminal sensory fiber stimulation induces morphological changes reflecting secretion in rat dura mater mast cells. Neuroscience 44: 97-112.
47. Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, et al. (2010). OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache 50: 921-936.
48. Dolly JO, O'Connell MA, (2012). Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr Opin Pharmacol 12: 100-108.
49. Dolly JO, Lawrence GW, Meng J, Wang J, Ovsepian SV, (2009). Neuro-exocytosis: botulinum toxins as inhibitory probes and versatile therapeutics. Curr Opin Pharmacol 9: 326-335.
50. Dong M, Yeh F, Tepp WH, Dean C, Johnson EA, Janz R, et al. (2006). SV2 is the protein receptor for botulinum neurotoxin A. Science 312: 592-596.
51. Dong M, Tepp WH, Liu H, Johnson EA, Chapman ER, (2007). Mechanism of botulinum neurotoxin B and G entry into hippocampal neurons. J Cell Biol 179: 1511-1522.
52. Duggan MJ, Quinn CP, Chaddock JA, Purkiss JR, Alexander FC, Doward S, et al. (2002). Inhibition of release of neurotransmitters from rat dorsal root ganglia by a novel conjugate of a Clostridium botulinum toxin A endopeptidase fragment and Erythrina cristagalli lectin. J Biol Chem 277: 34846-34852.
53. Durham PL, Cady R, Cady R, (2004). Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: implications for migraine therapy. Headache 44: 35-42.
54. Ebersberger A, (2001). Physiology of meningeal innervation: aspects and consequences of chemosensitivity of meningeal nociceptors. Microsc Res Tech 53: 138-146.
55. Eftekhari S, Warfvinge K, Blixt FW, Edvinsson L, (2013). Differentiation of nerve fibers storing CGRP and CGRP receptors in the peripheral trigeminovascular system. J Pain 14: 1289-1303.
56. Eijkelkamp N, Kavelaars A, Elsenbruch S, Schedlowski M, Holtmann G, Heijnen CJ, (2007). Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293: G749-G757.
57. Eleopra R, Tugnoli V, Rossetto O, De GD, Montecucco C, (1998). Different time courses of recovery after poisoning with botulinum neurotoxin serotypes A and E in humans. Neurosci Lett 256: 135-138.
58. Elkind AH, O'Carroll P, Blumenfeld A, DeGryse R, Dimitrova R, (2006). A series of three sequential, randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine prophylaxis. J Pain 7: 688-696.
59. Evers S, (2008). Treatment of migraine with prophylactic drugs. Expert Opin Pharmacother 9: 2565-2573.
60. Evers S, Vollmer-Haase J, Schwaag S, Rahmann A, Husstedt IW, Frese A, (2004). Botulinum toxin A in the prophylactic treatment of migraine-a randomized, double-blind, placebo-controlled study. Cephalalgia 24: 838-843.
61. Fabregat G, De AJ, Villanueva-Perez VL, Asensio-Samper JM, (2013). Subcutaneous and perineural botulinum toxin type a for neuropathic pain: a descriptive review. Clin J Pain 29: 1006-1012.
62. Filipovic B, Matak I, Bach-Rojecky L, Lackovic Z, (2012). Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy. PLoS ONE 7: e29803.
63. Fischer A, Montal M, (2007). Single molecule detection of intermediates during botulinum neurotoxin translocation across membranes. Proc Natl Acad Sci U S A 104: 10447-10452.
64. Fischer A, Nakai Y, Eubanks LM, Clancy CM, Tepp WH, Pellett S, et al. (2009). Bimodal modulation of the botulinum neurotoxin protein-conducting channel. Proc Natl Acad Sci U S A 106: 1330-1335.
65. Flynn TC, (2010). Botulinum toxin: examining duration of effect in facial aesthetic applications. Am J Clin Dermatol 11: 183-199.
66. Foran PG, Mohammed N, Lisk GO, Nagwaney S, Lawrence GW, Johnson E, et al. (2003). Evaluation of the therapeutic usefulness of botulinum neurotoxin B, C1, E, and F compared with the long lasting type A. Basis for distinct durations of inhibition of exocytosis in central neurons. J Biol Chem 278: 1363-1371.
67. Foreman RD, (2000). Integration of viscerosomatic sensory input at the spinal level. Prog Brain Res 122: 209-221.
68. Fotinou C, Emsley P, Black I, Ando H, Ishida H, Kiso M, et al. (2001). The crystal structure of tetanus toxin Hc fragment complexed with a synthetic GT1b analogue suggests cross-linking between ganglioside receptors and the toxin. J Biol Chem 276: 32274-32281.
69. Freitag FG, Diamond S, Diamond M, Urban G, (2008). Botulinum toxin type A in the treatment of chronic migraine without medication overuse. Headache 48: 201-209.
70. Gazerani P, Staahl C, Drewes AM, Arendt-Nielsen L, (2006). The effects of botulinum toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization. Pain 122: 315-325.
71. Gazerani P, Pedersen NS, Drewes AM, Arendt-Nielsen L, (2009a). Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin. Br J Dermatol 161: 737-745.
72. Gazerani P, Pedersen NS, Staahl C, Drewes AM, Arendt-Nielsen L, (2009b). Subcutaneous botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin. Pain 141: 60-69.
73. Grazzi L, (2013). Onabotulinum toxin A for treatment of chronic migraine with medication overuse. Neurol Sci 34 (Suppl. 1): S27-S28.
74. Gupta S, Amrutkar DV, Mataji A, Salmasi H, Hay-Schmidt A, Sheykhzade M, et al. (2010). Evidence for CGRP re-uptake in rat dura mater encephali. Br J Pharmacol 161: 1885-1898.
75. Habermann E, (1974). 125I-labeled neurotoxin from Clostridium botulinum A: preparation, binding to synaptosomes and ascent to the spinal cord. Naunyn Schmiedebergs Arch Pharmacol 281: 47-56.
76. Hamdy SM, Samir H, El-Sayed M, Adel N, Hasan R, (2009). Botulinum toxin: could it be an effective treatment for chronic tension-type headache? J Headache Pain 10: 27-34.
77. He Y, Elias CL, Huang YC, Gao X, Leung YM, Kang Y, et al. (2008). Botulinum neurotoxin A and neurotoxin E cleavage products of synaptosome-associated protein of 25 kd exhibit distinct actions on pancreatic islet beta-cell Kv2.1 channel gating. Pancreas 36: 10-17.
78. Huang PP, Khan I, Suhail MS, Malkmus S, Yaksh TL, (2011). Spinal botulinum neurotoxin B: effects on afferent transmitter release and nociceptive processing. PLoS ONE 6: e19126.
79. IASP (2013). International Association for the Study of Pain. Global Year Against Headache-Migraine. IASP. Available at: http://www.iasp-pain.org/AM/ Template.cfm?Section=Fact-Sheets4&Template=/CM/ContentDisplay. cfm&ContentID=14453. (accessed 1/31/2013).
80. Ikeda Y, Zabbarova IV, Birder LA, de Groat WC, McCarthy CJ, Hanna-Mitchell AT, et al. (2012). Botulinum neurotoxin serotype A suppresses neurotransmitter release from afferent as well as efferent nerves in the urinary bladder. Eur Urol 62: 1157-1164.
81. Jackson JL, Kuriyama A, Hayashino Y, (2012). Botulinum toxin A for prophylactic treatment of migraine and tension headaches in adults: a meta-analysis. JAMA 307: 1736-1745.
82. Jakubowski M, Levy D, Goor-Aryeh I, Collins B, Bajwa Z, Burstein R, (2005). Terminating migraine with allodynia and ongoing central sensitization using parenteral administration of COX1/COX2 inhibitors. Headache 45: 850-861.
83. Jakubowski M, McAllister PJ, Bajwa ZH, Ward TN, Smith P, Burstein R, (2006). Exploding vs. imploding headache in migraine prophylaxis with botulinum toxin A. Pain 125: 286-295.
84. Jansen I, Uddman R, Ekman R, Olesen J, Ottosson A, Edvinsson L, (1992). Distribution and effects of neuropeptide Y, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide in human middle meningeal arteries: comparison with cerebral and temporal arteries. Peptides 13: 527-536.
85. Juliano RL, Carver K, Cao C, Ming X, (2013). Receptors, endocytosis, and trafficking: the biological basis of targeted delivery of antisense and siRNA oligonucleotides. J Drug Target 21: 27-43.
86. Jurasinski CV, Lieth E, Dang Do AN, Schengrund CL, (2001). Correlation of cleavage of SNAP-25 with muscle function in a rat model of botulinum neurotoxin type A induced paralysis. Toxicon 39: 1309-1315.
87. Kakegawa W, Yuzaki M, (2005). A mechanism underlying AMPA receptor trafficking during cerebellar long-term potentiation. Proc Natl Acad Sci U S A 102: 17846-17851.
88. Kauffman JA, Way JF Jr, Siegel LS, Sellin LC, (1985). Comparison of the action of types A and F botulinum toxin at the rat neuromuscular junction. Toxicol Appl Pharmacol 79: 211-217.
89. Keller JE, Neale EA, Oyler G, Adler M, (1999). Persistence of botulinum neurotoxin action in cultured spinal cord cells. FEBS Lett 456: 137-142.
90. Keller JE, Cai F, Neale EA, (2004). Uptake of botulinum neurotoxin into cultured neurons. Biochemistry 43: 526-532.
91. Kowalski ML, Sliwinska-Kowalska M, Kaliner MA, (1990). Neurogenic inflammation, vascular permeability, and mast cells. II. Additional evidence indicating that mast cells are not involved in neurogenic inflammation. J Immunol 145: 1214-1221.
92. Kramer HH, Angerer C, Erbguth F, Schmelz M, Birklein F, (2003). Botulinum toxin a reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin. J Neurol 250: 188-193.
93. Laird JM, Martinez-Caro L, Garcia-Nicas E, Cervero F, (2001). A new model of visceral pain and referred hyperalgesia in the mouse. Pain 92: 335-342.
94. Lalli G, Bohnert S, Deinhardt K, Verastegui C, Schiavo G, (2003). The journey of tetanus and botulinum neurotoxins in neurons. Trends Microbiol 11: 431-437.
95. Lang T, (2007). SNARE proteins and 'membrane rafts. J Physiol 585: 693-698.
96. Lau CG, Takayasu Y, Rodenas-Ruano A, Paternain AV, Lerma J, Bennett MV, et al. (2010). SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking. J Neurosci 30: 242-254.
97. Lawrence GW, Foran P, Oliver DJ, (2002). Insights into a basis for incomplete inhibition by botulinum toxin A of Ca2+-evoked exocytosis from permeabilised chromaffin cells. Toxicology 181-182: 249-253.
98. Lawrence GW, Ovsepian SV, Wang J, Aoki KR, Dolly JO, (2012). Extravesicular intraneuronal migration of internalized botulinum neurotoxins without detectable inhibition of distal neurotransmission. Biochem J 441: 443-452.
99. Leggett J, Harper E, Waite E, Marks P, Martinez A, Lightman S, (2013). GHRH receptor-targeted botulinum neurotoxin selectively inhibits pulsatile GH secretion in male rats. Endocrinology 154: 3305-3318.
100. Levy D, Strassman AM, (2002). Mechanical response properties of A and C primary afferent neurons innervating the rat intracranial dura. J Neurophysiol 88: 3021-3031.
101. Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM, (2007). Mast cell degranulation activates a pain pathway underlying migraine headache. Pain 130: 166-176.
102. Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF, (2007). Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 68: 343-349.
103. Lipton RB, Varon SF, Grosberg B, McAllister PJ, Freitag F, Aurora SK, et al. (2011). OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine. Neurology 77: 1465-1472.
104. Littlewood NK, Todd AJ, Spike RC, Watt C, Shehab SA, (1995). The types of neuron in spinal dorsal horn which possess neurokinin-1 receptors. Neuroscience 66: 597-608.
105. Liu HT, Tsai SK, Kao MC, Hu JS, (2006). Botulinum toxin A relieved neuropathic pain in a case of post-herpetic neuralgia. Pain Med 7: 89-91.
106. Lucioni A, Bales GT, Lotan TL, McGehee DS, Cook SP, Rapp DE, (2008). Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int 101: 366-370.
107. Ludlow CL, Hallett M, Rhew K, Cole R, Shimizu T, Sakaguchi G, et al. (1992). Therapeutic use of type F botulinum toxin. N Engl J Med 326: 349-350.
108. Luvisetto S, Marinelli S, Cobianchi S, Pavone F, (2007). Anti-allodynic efficacy of botulinum neurotoxin A in a model of neuropathic pain. Neuroscience 145: 1-4.
109. Ma L, Nagai J, Sekino Y, Goto Y, Nakahira S, Ueda H, (2012). Single application of A2 NTX, a botulinum toxin A2 subunit, prevents chronic pain over long periods in both diabetic and spinal cord injury-induced neuropathic pain models. J Pharmacol Sci 119: 282-286.
110. Magalhaes E, Menezes C, Cardeal M, Melo A, (2010). Botulinum toxin type A versus amitriptyline for the treatment of chronic daily migraine. Clin Neurol Neurosurg 112: 463-466.
111. Mahant N, Clouston PD, Lorentz IT, (2000). The current use of botulinum toxin. J Clin Neurosci 7: 389-394.
112. Marchand-Pauvert V, Aymard C, Giboin LS, Dominici F, Rossi A, Mazzocchio R, (2013). Beyond muscular effects: depression of spinal recurrent inhibition after botulinum neurotoxin A. J Physiol 591: 1017-1029.
113. Marinelli S, Vacca V, Ricordy R, Uggenti C, Tata AM, Luvisetto S, et al. (2012). The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin A involves Schwann cells and astrocytes. PLoS ONE 7: e47977.
114. Marino MJ, Terashima T, Steinauer JJ, Eddinger KA, Yaksh TL, Xu Q, (2014). Botulinum toxin B in the sensory afferent: transmitter release, spinal activation, and pain behavior. Pain 155: 674-684.
115. Markowitz S, Saito K, Moskowitz MA, (1988). Neurogenically mediated plasma extravasation in dura mater: effect of ergot alkaloids. A possible mechanism of action in vascular headache. Cephalalgia 8: 83-91.
116. Matak I, Bach-Rojecky L, Filipovic B, Lackovic Z, (2011). Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience 186: 201-207.
117. Matak I, Riederer P, Lackovic Z, (2012). Botulinum toxin's axonal transport from periphery to the spinal cord. Neurochem Int 61: 236-239.
118. Matak I, Stracenski I, Lackovic Z, (2013). Comparison of analgesic effects of single versus repeated injection of botulinum toxin in orofacial formalin test in rats. J Neural Transm 120: 141-144.
119. Mathew NT, Jaffri SF, (2009). A double-blind comparison of onabotulinumtoxina (BOTOX) and topiramate (TOPAMAX) for the prophylactic treatment of chronic migraine: a pilot study. Headache 49: 1466-1478.
120. Mathew NT, Frishberg BM, Gawel M, Dimitrova R, Gibson J, Turkel C, (2005). Botulinum toxin type A (BOTOX) for the prophylactic treatment of chronic daily headache: a randomized, double-blind, placebo-controlled trial. Headache 45: 293-307.
121. McNaughton FL, Feindel WH, (1977). Innervation of intracranial structures: a reappraisal. In:, Rose FC, (ed.). Physiological Aspects of Clinical Neurology. Blackwell Scientific Publications: Oxford, pp. 279-293.
122. Meng J, Wang J, Lawrence G, Dolly JO, (2007). Synaptobrevin I mediates exocytosis of CGRP from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential. J Cell Sci 120: 2864-2874.
123. Meng J, Ovsepian SV, Wang J, Pickering M, Sasse A, Aoki KR, et al. (2009). Activation of TRPV1 mediates calcitonin gene-related peptide release, which excites trigeminal sensory neurons and is attenuated by a retargeted botulinum toxin with anti-nociceptive potential. J Neurosci 29: 4981-4992.
124. Molgo J, Comella JX, Angaut-Petit D, Pecot-Dechavassine M, Tabti N, Faille L, et al. (1990). Presynaptic actions of botulinal neurotoxins at vertebrate neuromuscular junctions. J Physiol (Paris) 84: 152-166.
125. Montal M, (2010). Botulinum neurotoxin: a marvel of protein design. Annu Rev Biochem 79: 591-617.
126. Montecucco C, Schiavo G, (1994). Mechanism of action of tetanus and botulinum neurotoxins. Mol Microbiol 13: 1-8.
127. Montell C, (2004). Exciting trips for TRPs. Nat Cell Biol 6: 690-692.
128. Morch CD, Hu JW, Arendt-Nielsen L, Sessle BJ, (2007). Convergence of cutaneous, musculoskeletal, dural and visceral afferents onto nociceptive neurons in the first cervical dorsal horn. Eur J Neurosci 26: 142-154.
129. Nilsson F, Nilsson T, Edvinsson L, Bjorkman S, Nordstrom CH, (1997). Effects of dihydroergotamine and sumatriptan on isolated human cerebral and peripheral arteries and veins. Acta Anaesthesiol Scand 41: 1257-1262.
130. Noma N, Tsuboi Y, Kondo M, Matsumoto M, Sessle BJ, Kitagawa J, et al. (2008). Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis and upper cervical cord following capsaicin injection into oral and craniofacial regions in rats. J Comp Neurol 507: 1428-1440.
131. Olesen J, (2013). ICHD-3 beta is published. Use it immediately. Cephalalgia 33: 627-628.
132. Olesen J, Ashina M, (2011). Emerging migraine treatments and drug targets. Trends Pharmacol Sci 32: 352-359.
133. Olesen J, Burstein R, Ashina M, Tfelt-Hansen P, (2009). Origin of pain in migraine: evidence for peripheral sensitisation. Lancet Neurol 8: 679-690.
134. Oshinsky ML, Gomonchareonsiri S, (2007). Episodic dural stimulation in awake rats: a model for recurrent headache. Headache 47: 1026-1036.
135. de Paiva A, Meunier FA, Molgo J, Aoki KR, Dolly JO, (1999). Functional repair of motor endplates after botulinum neurotoxin type A poisoning: biphasic switch of synaptic activity between nerve sprouts and their parent terminals. Proc Natl Acad Sci U S A 96: 3200-3205.
136. Park HJ, Lee Y, Lee J, Park C, Moon DE, (2006). The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain. Can J Anaesth 53: 470-477.
137. Park TH, (2013). The effects of botulinum toxin A on mast cell activity: preliminary results. Burns 39: 816-817.
138. Pawson, AJ, Sharman, JL, Benson, HE, Faccenda, E, Alexander, SP, Buneman, OP, et al. (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledge base of drug targets and their ligands. Nucleic Acids Research 42 (Database Issue): D1098-1106.
139. Peck MW, (2009). Biology and genomic analysis of Clostridium botulinum. Adv Microb Physiol 55: 183-265. 320.
140. Pellett S, (2012). Learning from the past: historical aspects of bacterial toxins as pharmaceuticals. Curr Opin Microbiol 15: 292-299.
141. Peroutka SJ, (2005). Neurogenic inflammation and migraine: implications for the therapeutics. Mol Interv 5: 304-311.
142. Petri S, Tolle T, Straube A, Pfaffenrath V, Stefenelli U, Ceballos-Baumann A, (2009). Botulinum toxin as preventive treatment for migraine: a randomized double-blind study. Eur Neurol 62: 204-211.
143. Piovesan EJ, Kowacs PA, Tatsui CE, Lange MC, Ribas LC, Werneck LC, (2001). Referred pain after painful stimulation of the greater occipital nerve in humans: evidence of convergence of cervical afferences on trigeminal nuclei. Cephalalgia 21: 107-109.
144. Piovesan EJ, Teive HG, Kowacs PA, Della Coletta MV, Werneck LC, Silberstein SD, (2005). An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 65: 1306-1308.
145. Porta M, (2000). A comparative trial of botulinum toxin type A and methylprednisolone for the treatment of tension-type headache. Curr Rev Pain 4: 31-35.
146. Ramachandran R, Bhatt DK, Ploug KB, Olesen J, Jansen-Olesen I, Hay-Schmidt A, et al. (2012). A naturalistic glyceryl trinitrate infusion migraine model in the rat. Cephalalgia 32: 73-84.
147. Ramachandran R, Bhatt DK, Ploug KB, Gupta S, Hay-Schmidt A, Jansen-Olesen I, et al. (2014). Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN induced neuronal activation. Cephalalgia 34: 136-147.
148. Ranoux D, Attal N, Morain F, Bouhassira D, (2008). Botulinum toxin type A induces direct analgesic effects in chronic neuropathic pain. Ann Neurol 64: 274-283.
149. Rapp DE, Turk KW, Bales GT, Cook SP, (2006). Botulinum toxin type a inhibits calcitonin gene-related peptide release from isolated rat bladder. J Urol 175: 1138-1142.
150. Ray BS, Wolff HG, (1940). Experimental studies on headache; pain-sensitive structures of the head and their significance in headache. Arch Surg 41: 813-856.
151. Relja M, Poole AC, Schoenen J, Pascual J, Lei X, Thompson C, (2007). A multicentre, double-blind, randomized, placebo-controlled, parallel group study of multiple treatments of botulinum toxin type A (BoNTA) for the prophylaxis of episodic migraine headaches. Cephalalgia 27: 492-503.
152. Restani L, Antonucci F, Gianfranceschi L, Rossi C, Rossetto O, Caleo M, (2011). Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A). J Neurosci 31: 15650-15659.
153. Restani L, Giribaldi F, Manich M, Bercsenyi K, Menendez G, Rossetto O, et al. (2012). Botulinum neurotoxins A and E undergo retrograde axonal transport in primary motor neurons. PLoS Pathog 8: e1003087.
154. Robinson DR, Gebhart GF, (2008). Inside information: the unique features of visceral sensation. Mol Interv 8: 242-253.
155. Roch M, Messlinger K, Kulchitsky V, Tichonovich O, Azev O, Koulchitsky S, (2007). Ongoing activity in trigeminal wide-dynamic range neurons is driven from the periphery. Neuroscience 150: 681-691.
156. Rossetto O, Montecucco C, (2008). Presynaptic neurotoxins with enzymatic activities. Handb Exp Pharmacol 184: 129-170.
157. Rothman JE, (1994). Mechanisms of intracellular transport. Nature 372: 55-63.
158. Ruiz HC, Bermejo P, (2008). [Botulinum toxin type A in the treatment of neuropathic pain in a case of postherpetic neuralgia]. Neurologia 23: 259-262.
159. Rummel A, (2013). Double receptor anchorage of botulinum neurotoxins accounts for their exquisite neurospecificity. Curr Top Microbiol Immunol 364: 61-90.
160. Rummel A, Eichner T, Weil T, Karnath T, Gutcaits A, Mahrhold S, et al. (2007). Identification of the protein receptor binding site of botulinum neurotoxins B and G proves the double-receptor concept. Proc Natl Acad Sci U S A 104: 359-364.
161. Russell MB, Rasmussen BK, Thorvaldsen P, Olesen J, (1995). Prevalence and sex-ratio of the subtypes of migraine. Int J Epidemiol 24: 612-618.
162. Samton J, Mauskop A, (2006). Treatment of headaches with botulinum toxin. Expert Rev Neurother 6: 313-322.
163. Sandrini G, Perrotta A, Tassorelli C, Torelli P, Brighina F, Sances G, et al. (2011). Botulinum toxin type-A in the prophylactic treatment of medication-overuse headache: a multicenter, double-blind, randomized, placebo-controlled, parallel group study. J Headache Pain 12: 427-433.
164. Saper JR, Mathew NT, Loder EW, DeGryse R, Vandenburgh AM, (2007). A double-blind, randomized, placebo-controlled comparison of botulinum toxin type a injection sites and doses in the prevention of episodic migraine. Pain Med 8: 478-485.
165. Schenk U, Verderio C, Benfenati F, Matteoli M, (2003). Regulated delivery of AMPA receptor subunits to the presynaptic membrane. EMBO J 22: 558-568.
166. Schiavo G, Shone CC, Bennett MK, Scheller RH, Montecucco C, (1995). Botulinum neurotoxin type C cleaves a single Lys-Ala bond within the carboxyl-terminal region of syntaxins. J Biol Chem 270: 10566-10570.
167. Schiavo G, Matteoli M, Montecucco C, (2000). Neurotoxins affecting neuroexocytosis. Physiol Rev 80: 717-766.
168. Schueler M, Messlinger K, Dux M, Neuhuber WL, De CR, (2013). Extracranial projections of meningeal afferents and their impact on meningeal nociception and headache. Pain 154: 1622-1631.
169. Serrano D, Manack AN, Reed ML, Buse DC, Varon SF, Lipton RB, (2013). Cost and predictors of lost productive time in chronic migraine and episodic migraine: results from the American Migraine Prevalence and Prevention (AMPP) Study. Value Health 16: 31-38.
170. Shan XF, Xu H, Cai ZG, Wu LL, Yu GY, (2013). Botulinum toxin A inhibits salivary secretion of rabbit submandibular gland. Int J Oral Sci 5: 217-223.
171. Shimizu T, Shibata M, Toriumi H, Iwashita T, Funakubo M, Sato H, et al. (2012). Reduction of TRPV1 expression in the trigeminal system by botulinum neurotoxin type-A. Neurobiol Dis 48: 367-378.
172. Silberstein S, Mathew N, Saper J, Jenkins S, (2000). Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine Clinical Research Group. Headache 40: 445-450.
173. Silberstein SD, Blumenfeld AM, Cady RK, Turner IM, Lipton RB, Diener HC, et al. (2013). OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline. J Neurol Sci 331: 48-56.
174. Simpson L, (2013). The life history of a botulinum toxin molecule. Toxicon 68: 40-59.
175. Sloop RR, Cole BA, Escutin RO, (1997). Human response to botulinum toxin injection: type B compared with type A. Neurology 49: 189-194.
176. Smyth LM, Breen LT, Mutafova-Yambolieva VN, (2006). Nicotinamide adenine dinucleotide is released from sympathetic nerve terminals via a botulinum neurotoxin A-mediated mechanism in canine mesenteric artery. Am J Physiol Heart Circ Physiol 290: H1818-H1825.
177. Steiger HJ, Meakin CJ, (1984). The meningeal representation in the trigeminal ganglion-an experimental study in the cat. Headache 24: 305-309.
178. Steinberg JP, Huganir RL, Linden DJ, (2004). N-ethylmaleimide-sensitive factor is required for the synaptic incorporation and removal of AMPA receptors during cerebellar long-term depression. Proc Natl Acad Sci U S A 101: 18212-18216.
179. Stenmark P, Dupuy J, Imamura A, Kiso M, Stevens RC, (2008). Crystal structure of botulinum neurotoxin type A in complex with the cell surface co-receptor GT1b-insight into the toxin-neuron interaction. PLoS Pathog 4: e1000129.
180. Strassman A, Mason P, Moskowitz M, Maciewicz R, (1986). Response of brainstem trigeminal neurons to electrical stimulation of the dura. Brain Res 379: 242-250.
181. Strassman AM, Levy D, (2006). Response properties of dural nociceptors in relation to headache. J Neurophysiol 95: 1298-1306.
182. Strassman AM, Mineta Y, Vos BP, (1994). Distribution of fos-like immunoreactivity in the medullary and upper cervical dorsal horn produced by stimulation of dural blood vessels in the rat. J Neurosci 14: 3725-3735.
183. Strassman AM, Raymond SA, Burstein R, (1996). Sensitization of meningeal sensory neurons and the origin of headaches. Nature 384: 560-564.
184. Strecker T, Messlinger K, (2003). [Neuropeptide release in the dura mater encephali in response to nitric oxide-relevance for the development of vascular headaches?]. Schmerz 17: 179-184.
185. Tao YX, (2012). AMPA receptor trafficking in inflammation-induced dorsal horn central sensitization. Neurosci Bull 28: 111-120.
186. Torii Y, Akaike N, Harakawa T, Kato K, Sugimoto N, Goto Y, et al. (2011). Type A1 but not type A2 botulinum toxin decreases the grip strength of the contralateral foreleg through axonal transport from the toxin-treated foreleg of rats. J Pharmacol Sci 117: 275-285.
187. Tugnoli V, Capone JG, Eleopra R, Quatrale R, Sensi M, Gastaldo E, et al. (2007). Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin. Pain 130: 76-83.
188. Uddman R, Edvinsson L, Ekman R, Kingman T, McCulloch J, (1985). Innervation of the feline cerebral vasculature by nerve fibers containing calcitonin gene-related peptide: trigeminal origin and co-existence with substance P. Neurosci Lett 62: 131-136.
189. Uddman R, Tajti J, Hou M, Sundler F, Edvinsson L, (2002). Neuropeptide expression in the human trigeminal nucleus caudalis and in the cervical spinal cord C1 and C2. Cephalalgia 22: 112-116.
190. Vo AH, Satori R, Jabbari B, Green J, Killgore WD, Labutta R, et al. (2007). Botulinum toxin type-a in the prevention of migraine: a double-blind controlled trial. Aviat Space Environ Med 78: B113-B118.
191. Voller B, Sycha T, Gustorff B, Schmetterer L, Lehr S, Eichler HG, et al. (2003). A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin A. Neurology 61: 940-944.
192. Wang D, Zhang Z, Dong M, Sun S, Chapman ER, Jackson MB, (2011). Syntaxin requirement for Ca2+-triggered exocytosis in neurons and endocrine cells demonstrated with an engineered neurotoxin. Biochemistry 50: 2711-2713.
193. Wheeler AH, (1998). Botulinum toxin A, adjunctive therapy for refractory headaches associated with pericranial muscle tension. Headache 38: 468-471.
194. Wiegand H, Erdmann G, Wellhoner HH, (1976). 125I-labelled botulinum A neurotoxin: pharmacokinetics in cats after intramuscular injection. Naunyn Schmiedebergs Arch Pharmacol 292: 161-165.
195. Xiao L, Mackey S, Hui H, Xong D, Zhang Q, Zhang D, (2010). Subcutaneous injection of botulinum toxin a is beneficial in postherpetic neuralgia. Pain Med 11: 1827-1833.
196. Yaksh TL, Provencher JC, Rathbun ML, Kohn FR, (1999). Pharmacokinetics and efficacy of epidurally delivered sustained-release encapsulated morphine in dogs. Anesthesiology 90: 1402-1412.
197. Yamamoto H, Ida T, Tsutsuki H, Mori M, Matsumoto T, Kohda T, et al. (2012). Specificity of botulinum protease for human VAMP family proteins. Microbiol Immunol 56: 245-253.
198. Yuan RY, Sheu JJ, Yu JM, Chen WT, Tseng IJ, Chang HH, et al. (2009). Botulinum toxin for diabetic neuropathic pain: a randomized double-blind crossover trial. Neurology 72: 1473-1478.
199. Zanner R, Gratzl M, Prinz C, (2002). Circle of life of secretory vesicles in gastric enterochromaffin-like cells. Ann N Y Acad Sci 971: 389-396.
200. Zhang X, Kainz V, Zhao J, Strassman AM, Levy D, (2013). Vascular ERK mediates migraine-related sensitization of meningeal nociceptors. Ann Neurol 73: 741-750.
201. Zhang XC, Strassman AM, Burstein R, Levy D, (2007). Sensitization and activation of intracranial meningeal nociceptors by mast cell mediators. J Pharmacol Exp Ther 322: 806-812.
202. Zhang XC, Kainz V, Burstein R, Levy D, (2011). Tumor necrosis factor-alpha induces sensitization of meningeal nociceptors mediated via local COX and p38 MAP kinase actions. Pain 152: 140-149.
203. Zwetsloot CP, Caekebeke JF, Jansen JC, Odink J, Ferrari MD, (1991). Blood flow velocity changes in migraine attacks-a transcranial Doppler study. Cephalalgia 11: 103-107.