Current status and future directions of botulinum neurotoxins for targeting pain processing

Toxins

Volumn 7, Issue 11, 2015, Pages 4519-4563

  Pellett, Sabine ^a   Yaksh, Tony L ^b   Ramachandran, Roshni ^b  

^a UNIVERSITY OF WISCONSIN MADISON   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

BoNT; Botulinum neurotoxin; Glia; Neurotransmitter; Pain; Primary afferent; SNAREs; Spinal cord

Indexed keywords

BOTULINUM NEUROTOXIN A1; BOTULINUM NEUROTOXIN B1; BOTULINUM TOXIN; CAPSAICIN; SNARE PROTEIN; UNCLASSIFIED DRUG; NEUROTOXIN;

CLOSTRIDIUM BOTULINUM; CLOSTRIDIUM BUTYRICUM; CLOSTRIDIUM SPOROGENES; DRUG ADMINISTRATION ROUTE; DRUG RESEARCH; DRUG TARGETING; ENZYME ACTIVITY; GLIA CELL; INFLAMMATION; LIGHT CHAIN; MIGRAINE; NEUROPATHIC PAIN; NOCICEPTION; NOCICEPTIVE PAIN; PERIPHERAL NERVE INJURY; PROTEIN CLEAVAGE; PROTEIN POLYMORPHISM; REVIEW; SENSORY NERVE; SEROTYPE; SPECIES DIFFERENCE; SYNAPTIC TRANSMISSION; TISSUE INJURY; ANIMAL; CHEMISTRY; COMPLICATION; HUMAN; MOLECULAR MODEL; PAIN; PATHOPHYSIOLOGY; PERIPHERAL NERVOUS SYSTEM DISEASES;

ANIMALS; BOTULINUM TOXINS; HUMANS; INFLAMMATION; MODELS, MOLECULAR; NEUROTOXINS; PAIN; PERIPHERAL NERVOUS SYSTEM DISEASES;

EID: 84946854526     PISSN: None     EISSN: 20726651     Source Type: Journal    
DOI: 10.3390/toxins7114519     Document Type: Review

References (321)

1. Johnson, E.A.; Montecucco, C. BOTULISM. In Handbook of Clinical Neurology ; Andrew, G.E., Ed.; Elsevier: Amsterdam, The Netherlands, 2008; Volume 91, pp. 333-368.
2. Drachman, D.B. Botulinum toxin as a tool for research on the nervous system. In Neuropoisons. Their Physiological Actions ; Simpson, L.L., Ed.; Plenum: New York, NY, USA, 1971; Volume 1, pp. 325-347.
3. Scott, A.B.; Rosenbaum, A.; Collins, C.C. Pharmacologic weakening of extraocular muscles. Investig. Ophthalmol. 1973, 12, 924-927.
4. Scott, A.B. Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J. Pediatr. Ophthalmol. Strabismus 1980, 17, 21-25.
5. Schantz, E.J.; Kautter, D.A. Standardized assay for clostridium botulinum toxins. J. AOAC. 1978, 61, 96-99.
6. Dressler, D. Clinical applications of botulinum toxin. Curr. Opin. Microbiol. 2012, 15, 325-336.
7. Truong, D.D.; Stenner, A.; Reichel, G. Current clinical applications of botulinum toxin. Curr. Pharm. Des. 2009, 15, 3671-3680.
8. Pantano, S.; Montecucco, C. The blockade of the neurotransmitter release apparatus by botulinum neurotoxins. Cell Mol. Life Sci. 2014, 71, 793-811.
9. Brin, M.F.; Fahn, S.; Moskowitz, C.; Friedman, A.; Shale, H.M.; Greene, P.E.; Blitzer, A.; List, T.; Lange, D.; Lovelace, R.E.; et al. Localized injections of botulinum toxin for the treatment of focal dystonia and hemifacial spasm. Mov. Disord. 1987, 2, 237-254.
10. Whitcup, S.M.; Turkel, C.C.; DeGryse, R.E.; Brin, M.F. Development of onabotulinumtoxina for chronic migraine. Ann. N. Y. Acad. Sci. 2014, 1329, 67-80.
11. Robertson, C.E.; Garza, I. Critical analysis of the use of onabotulinumtoxina (botulinum toxin type A) in migraine. Neuropsychiatr. Dis. Treat. 2012, 8, 35-48.
12. Frampton, J.E. OnabotulinumtoxinA (BOTOX®): A review of its use in the prophylaxis of headaches in adults with chronic migraine. Drugs 2012, 72, 825-845.
13. Dodick, D.W.; Turkel, C.C.; DeGryse, R.E.; Aurora, S.K.; Silberstein, S.D.; Lipton, R.B.; Diener, H.C.; Brin, M.F. Onabotulinumtoxina for treatment of chronic migraine: Pooled results from the double-blind, randomized, placebo-controlled phases of the preempt clinical program. Headache 2010, 50, 921-936.
14. Diener, H.C.; Dodick, D.W.; Aurora, S.K.; Turkel, C.C.; DeGryse, R.E.; Lipton, R.B.; Silberstein, S.D.; Brin, M.F. Onabotulinumtoxina for treatment of chronic migraine: Results from the double-blind, randomized, placebo-controlled phase of the preempt 2 trial. Cephalalgia Int. J. Headache 2010, 30, 804-814.
15. Barrientos, N.; Chana, P. Botulinum toxin type A in prophylactic treatment of migraine headaches: A preliminary study. J. Headache Pain 2003, 4, 146-151.
16. Silberstein, S.; Mathew, N.; Saper, J.; Jenkins, S. Botulinum toxin type A as a migraine preventive treatment. For the BoTOX migraine clinical research group. Headache 2000, 40, 445-450.
17. Anand, K.S.; Prasad, A.; Singh, M.M.; Sharma, S.; Bala, K. Botulinum toxin type A in prophylactic treatment of migraine. Am. J. Therapeutics 2006, 13, 183-187.
18. Aurora, S.K.; Winner, P.; Freeman, M.C.; Spierings, E.L.; Heiring, J.O.; DeGryse, R.E.; VanDenburgh, A.M.; Nolan, M.E.; Turkel, C.C. Onabotulinumtoxina for treatment of chronic migraine: Pooled analyses of the 56-week preempt clinical program. Headache 2011, 51, 1358-1373.
19. Fadeyi, M.O.; Adams, Q.M. Use of botulinum toxin type B for migraine and tension headaches. Am. J. Health-Syst. Pharm. 2002, 59, 1860-1862.
20. Grogan, P.M.; Alvarez, M.V.; Jones, L. Headache direction and aura predict migraine responsiveness to rimabotulinumtoxin B. Headache 2013, 53, 126-136.
21. Lipton, R.B.; Varon, S.F.; Grosberg, B.; McAllister, P.J.; Freitag, F.; Aurora, S.K.; Dodick, D.W.; Silberstein, S.D.; Diener, H.C.; DeGryse, R.E.; et al. Onabotulinumtoxina improves quality of life and reduces impact of chronic migraine. Neurology 2011, 77, 1465-1472.
22. Hollanda, L.; Monteiro, L.; Melo, A. Botulinum toxin type A for cephalic cutaneous allodynia in chronic migraine: A randomized, double-blinded, placebo-controlled trial. Neurol. Int. 2014, 6, 5133.
23. Elkind, A.H.; O'Carroll, P.; Blumenfeld, A.; DeGryse, R.; Dimitrova, R. A series of three sequential, randomized, controlled studies of repeated treatments with botulinum toxin type A for migraine prophylaxis. J. Pain 2006, 7, 688-696.
24. Relja, M.; Poole, A.C.; Schoenen, J.; Pascual, J.; Lei, X.; Thompson, C. 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 Int. J. Headache 2007, 27, 492-503.
25. Gady, J.; Ferneini, E.M. Botulinum toxin A and headache treatment. Conn. Med. 2013, 77, 165-166.
26. Peck, M.W. Biology and genomic analysis of clostridium botulinum. Adv. Microb. Physiol. 2009, 55, 183-265.
27. Stringer, S.C.; Carter, A.T.; Webb, M.D.; Wachnicka, E.; Crossman, L.C.; Sebaihia, M.; Peck, M.W. Genomic and physiological variability within group II (non-proteolytic) clostridium botulinum. BMC genomics 2013, 14, 333.
28. Hill, K.K.; Smith, T.J. Genetic diversity within clostridium botulinum serotypes, botulinum neurotoxin gene clusters and toxin subtypes. Curr. Top. Microbiol. Immunol. 2013, 364, 1-20.
29. Gimenez, D.F.; Gimenez, J.A. The typing of botulinal neurotoxins. Int. J. Food Microbiol. 1995, 27, 1-9.
30. Montal, M. Botulinum neurotoxin: A marvel of protein design. Ann. Rev. Biochem. 2010, 79, 591-617.
31. Fischer, A.; Montal, M. Single molecule detection of intermediates during botulinum neurotoxin translocation across membranes. Proc. Natl. Acad. Sci. USA 2007, 104, 10447-10452.
32. Fischer, A.; Nakai, Y.; Eubanks, L.M.; Clancy, C.M.; Tepp, W.H.; Pellett, S.; Dickerson, T.J.; Johnson, E.A.; Janda, K.D.; Montal, M. Bimodal modulation of the botulinum neurotoxin protein-conducting channel. Proc. Natl. Acad. Sci. USA 2009, 106, 1330-1335.
33. Pirazzini, M.; Azarnia Tehran, D.; Zanetti, G.; Megighian, A.; Scorzeto, M.; Fillo, S.; Shone, C.C.; Binz, T.; Rossetto, O.; Lista, F.; et al. Thioredoxin and its reductase are present on synaptic vesicles, and their inhibition prevents the paralysis induced by botulinum neurotoxins. Cell Rep. 2014, 8, 1870-1878.
34. Montecucco, C.; Schiavo, G. Mechanism of action of tetanus and botulinum neurotoxins. Mol. Microbiol. 1994, 13, 1-8.
35. Whitemarsh, R.C.; Tepp, W.H.; Johnson, E.A.; Pellett, S. Persistence of botulinum neurotoxin a subtypes 1-5 in primary rat spinal cord cells. PLoS ONE 2014, 9, e90252.
36. Lacy, D.B.; Tepp, W.; Cohen, A.C.; DasGupta, B.R.; Stevens, R.C. Crystal structure of botulinum neurotoxin type A and implications for toxicity. Nat. Struct. Biol. 1998, 5, 898-902.
37. Mahowald, M.L.; Singh, J.A.; Dykstra, D. Long term effects of intra-articular botulinum toxin A for refractory joint pain. Neurotox. Res. 2006, 9, 179-188.
38. Castiglione, A.; Bagnato, S.; Boccagni, C.; Romano, M.C.; Galardi, G. Efficacy of intra-articular injection of botulinum toxin type A in refractory hemiplegic shoulder pain. Arch. Phys. Med. Rehabil. 2011, 92, 1034-1037.
39. Singh, J.A.; Fitzgerald, P.M. Botulinum toxin for shoulder pain: A cochrane systematic review. J. Rheumatol. 2011, 38, 409-418.
40. Boon, A.J.; Smith, J.; Dahm, D.L.; Sorenson, E.J.; Larson, D.R.; Fitz-Gibbon, P.D.; Dykstra, D.D.; Singh, J.A. Efficacy of intra-articular botulinum toxin type A in painful knee osteoarthritis: A pilot study. PM & R J. Injury Funct. Rehabil. 2010, 2, 268-276.
41. Ranoux, D.; Attal, N.; Morain, F.; Bouhassira, D. Botulinum toxin type a induces direct analgesic effects in chronic neuropathic pain. Ann. Neurol. 2008, 64, 274-283.
42. Fabregat, G.; Asensio-Samper, J.M.; Palmisani, S.; Villanueva-Perez, V.L.; de Andres, J. Subcutaneous botulinum toxin for chronic post-thoracotomy pain. Pain Pract. 2013, 13, 231-234.
43. Kitamura, Y.; Matsuka, Y.; Spigelman, I.; Ishihara, Y.; Yamamoto, Y.; Sonoyama, W.; Kamioka, H.; Yamashiro, T.; Kuboki, T.; Oguma, K. Botulinum toxin type A (150 kda) decreases exaggerated neurotransmitter release from trigeminal ganglion neurons and relieves neuropathy behaviors induced by infraorbital nerve constriction. Neuroscience 2009, 159, 1422-1429.
44. Piovesan, E.J.; Teive, H.G.; Kowacs, P.A.; Della Coletta, M.V.; Werneck, L.C.; Silberstein, S.D. An open study of botulinum-A toxin treatment of trigeminal neuralgia. Neurology 2005, 65, 1306-1308.
45. Zuniga, C.; Diaz, S.; Piedimonte, F.; Micheli, F. Beneficial effects of botulinum toxin type A in trigeminal neuralgia. Arquivos Neuro-Psiquiatria 2008, 66, 500-503.
46. Turk, U.; Ilhan, S.; Alp, R.; Sur, H. Botulinum toxin and intractable trigeminal neuralgia. Clin. Neuropharmacol. 2005, 28, 161-162.
47. Wu, C.J.; Lian, Y.J.; Zheng, Y.K.; Zhang, H.F.; Chen, Y.; Xie, N.C.; Wang, L.J. Botulinum toxin type A for the treatment of trigeminal neuralgia: Results from a randomized, double-blind, placebo-controlled trial. Cephalalgia Int. J. Headache 2012, 32, 443-450.
48. Guardiani, E.; Sadoughi, B.; Blitzer, A.; Sirois, D. A new treatment paradigm for trigeminal neuralgia using botulinum toxin type A. Laryngoscope 2014, 124, 413-417.
49. Liu, H.T.; Tsai, S.K.; Kao, M.C.; Hu, J.S. Botulinum toxin A relieved neuropathic pain in a case of post-herpetic neuralgia. Pain Med. 2006, 7, 89-91.
50. Ruiz Huete, C.; Bermejo, P. Botulinum toxin type A in the treatment of neuropathic pain in a case of postherpetic neuralgia. Neurologia 2008, 23, 259-262.
51. Xiao, L.; Mackey, S.; Hui, H.; Xong, D.; Zhang, Q.; Zhang, D. Subcutaneous injection of botulinum toxin A is beneficial in postherpetic neuralgia. Pain Med. 2010, 11, 1827-1833.
52. Yuan, R.Y.; Sheu, J.J.; Yu, J.M.; Chen, W.T.; Tseng, I.J.; Chang, H.H.; Hu, C.J. Botulinum toxin for diabetic neuropathic pain: A randomized double-blind crossover trial. Neurology 2009, 72, 1473-1478.
53. Jabbari, B. Evidence based medicine in the use of botulinum toxin for back pain. J. Neural Transm. 2008, 115, 637-640.
54. Jabbari, B. Treatment of chronic low back pain with botulinum neurotoxins. Curr. Pain Headache Rep. 2007, 11, 352-358.
55. Cheshire, W.P.; Abashian, S.W.; Mann, J.D. Botulinum toxin in the treatment of myofascial pain syndrome. Pain 1994, 59, 65-69.
56. Wheeler, A.H.; Goolkasian, P.; Gretz, S.S. A randomized, double-blind, prospective pilot study of botulinum toxin injection for refractory, unilateral, cervicothoracic, paraspinal, myofascial pain syndrome. Spine 1998, 23, 1662-1666.
57. Gazerani, P.; Pedersen, N.S.; Staahl, C.; Drewes, A.M.; Arendt-Nielsen, L. Subcutaneous botulinum toxin type A reduces capsaicin-induced trigeminal pain and vasomotor reactions in human skin. Pain 2009, 141, 60-69.
58. Gazerani, P.; Staahl, C.; Drewes, A.M.; Arendt-Nielsen, L. The effects of botulinum toxin type A on capsaicin-evoked pain, flare, and secondary hyperalgesia in an experimental human model of trigeminal sensitization. Pain 2006, 122, 315-325.
59. Carmichael, N.M.; Dostrovsky, J.O.; Charlton, M.P. Peptide-mediated transdermal delivery of botulinum neurotoxin type A reduces neurogenic inflammation in the skin. Pain 2010, 149, 316-324.
60. Tugnoli, V.; Capone, J.G.; Eleopra, R.; Quatrale, R.; Sensi, M.; Gastaldo, E.; Tola, M.R.; Geppetti, P. Botulinum toxin type A reduces capsaicin-evoked pain and neurogenic vasodilatation in human skin. Pain 2007, 130, 76-83.
61. Schulte-Mattler, W.J.; Opatz, O.; Blersch, W.; May, A.; Bigalke, H.; Wohlfahrt, K. Botulinum toxin A does not alter capsaicin-induced pain perception in human skin. J. Neurol. Sci. 2007, 260, 38-42.
62. Blersch, W.; Schulte-Mattler, W.J.; Przywara, S.; May, A.; Bigalke, H.; Wohlfarth, K. Botulinum toxin A and the cutaneous nociception in humans: A prospective, double-blind, placebo-controlled, randomized study. J. Neurol. Sci. 2002, 205, 59-63.
63. Voller, B.; Sycha, T.; Gustorff, B.; Schmetterer, L.; Lehr, S.; Eichler, H.G.; Auff, E.; Schnider, P. A randomized, double-blind, placebo controlled study on analgesic effects of botulinum toxin A. Neurology 2003, 61, 940-944.
64. Da Silva, L.B.; Kulas, D.; Karshenas, A.; Cairns, B.E.; Bach, F.W.; Arendt-Nielsen, L.; Gazerani, P. Time course analysis of the effects of botulinum neurotoxin type A on pain and vasomotor responses evoked by glutamate injection into human temporalis muscles. Toxins 2014, 6, 592-607.
65. Sycha, T.; Samal, D.; Chizh, B.; Lehr, S.; Gustorff, B.; Schnider, P.; Auff, E. A lack of antinociceptive or antiinflammatory effect of botulinum toxin A in an inflammatory human pain model. Anesth. Analg. 2006, 102, 509-516.
66. Cui, M.; Khanijou, S.; Rubino, J.; Aoki, K.R. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain 2004, 107, 125-133.
67. Marino, M.J.; Terashima, T.; Steinauer, J.J.; Eddinger, K.A.; Yaksh, T.L.; Xu, Q. Botulinum toxin B in the sensory afferent: Transmitter release, spinal activation, and pain behavior. Pain 2014, 155, 674-684.
68. Marinelli, S.; Luvisetto, S.; Cobianchi, S.; Makuch, W.; Obara, I.; Mezzaroma, E.; Caruso, M.; Straface, E.; Przewlocka, B.; Pavone, F. Botulinum neurotoxin type A counteracts neuropathic pain and facilitates functional recovery after peripheral nerve injury in animal models. Neuroscience 2010, 171, 316-328.
69. Ma, L.; Nagai, J.; Sekino, Y.; Goto, Y.; Nakahira, S.; Ueda, H. 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. 2012, 119, 282-286.
70. Matak, I.; Lackovic, Z. Botulinum toxin A, brain and pain. Prog. Neurobiol. 2014, 119-120, 39-59.
71. Matak, I.; Bach-Rojecky, L.; Filipovic, B.; Lackovic, Z. Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin A. Neuroscience 2011, 186, 201-207.
72. Vacca, V.; Marinelli, S.; Eleuteri, C.; Luvisetto, S.; Pavone, F. Botulinum neurotoxin A enhances the analgesic effects on inflammatory pain and antagonizes tolerance induced by morphine in mice. Brain Behav. Immun. 2012, 26, 489-499.
73. Luvisetto, S.; Marinelli, S.; Lucchetti, F.; Marchi, F.; Cobianchi, S.; Rossetto, O.; Montecucco, C.; Pavone, F. Botulinum neurotoxins and formalin-induced pain: Central vs. Peripheral effects in mice. Brain Res. 2006, 1082, 124-131.
74. Filipovic, B.; Matak, I.; Bach-Rojecky, L.; Lackovic, Z. Central action of peripherally applied botulinum toxin type A on pain and dural protein extravasation in rat model of trigeminal neuropathy. PLoS ONE 2012, 7, e29803.
75. Ramachandran, R.; Lam, C.; Yaksh, T.L. Botulinum toxin in migraine: Role of transport in trigemino-somatic and trigemino-vascular afferents. Neurobiol. Dis. 2015, 79, 111-122.
76. Bach-Rojecky, L.; Lackovic, Z. Antinociceptive effect of botulinum toxin type A in rat model of carrageenan and capsaicin induced pain. Croat. Med. J. 2005, 46, 201-208.
77. Bach-Rojecky, L.; Dominis, M.; Lackovic, Z. Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation. Fundam. Clin. Pharmacol. 2008, 22, 503-509.
78. Favre-Guilmard, C.; Auguet, M.; Chabrier, P.E. Different antinociceptive effects of botulinum toxin type A in inflammatory and peripheral polyneuropathic rat models. Eur. J. Pharmacol. 2009, 617, 48-53.
79. Shin, M.C.; Yukihira, T.; Ito, Y.; Akaike, N. Antinociceptive effects of A1 and A2 type botulinum toxins on carrageenan-induced hyperalgesia in rat. Toxicon 2013, 64, 12-19.
80. Krug, H.E.; Frizelle, S.; McGarraugh, P.; Mahowald, M.L. Pain behavior measures to quantitate joint pain and response to neurotoxin treatment in murine models of arthritis. Pain Med. 2009, 10, 1218-1228.
81. Heikkila, H.M.; Hielm-Bjorkman, A.K.; Morelius, M.; Larsen, S.; Honkavaara, J.; Innes, J.F.; Laitinen-Vapaavuori, O.M. Intra-articular botulinum toxin A for the treatment of osteoarthritic joint pain in dogs: A randomized, double-blinded, placebo-controlled clinical trial. Vet. J. 2014, 200, 162-169.
82. Hadley, H.S.; Wheeler, J.L.; Petersen, S.W. Effects of intra-articular botulinum toxin type A (Botox®) in dogs with chronic osteoarthritis. Vet. Comp. Orthop. Traumatol. 2010, 23, 254-258.
83. Rialland, P.; Authier, S.; Guillot, M.; del Castillo, J.R.; Veilleux-Lemieux, D.; Frank, D.; Gauvin, D.; Troncy, E. Validation of orthopedic postoperative pain assessment methods for dogs: A prospective, blinded, randomized, placebo-controlled study. PLoS ONE 2012, 7, e49480.
84. Park, H.J.; Marino, M.J.; Rondon, E.S.; Xu, Q.; Yaksh, T.L. The effects of intraplantar and intrathecal botulinum toxin type B on tactile allodynia in mono and polyneuropathy in the mouse. Anesth. Analg. 2015, 121, 229-238.
85. Park, H.J.; Lee, Y.; Lee, J.; Park, C.; Moon, D.E. The effects of botulinum toxin A on mechanical and cold allodynia in a rat model of neuropathic pain. Can. J. Anaesth. 2006, 53, 470-477.
86. Xiao, L.; Cheng, J.; Dai, J.; Zhang, D. Botulinum toxin decreases hyperalgesia and inhibits P2X3 receptor over-expression in sensory neurons induced by ventral root transection in rats. Pain Med. 2011, 12, 1385-1394.
87. Xiao, L.; Cheng, J.; Zhuang, Y.; Qu, W.; Muir, J.; Liang, H.; Zhang, D. Botulinum toxin type A reduces hyperalgesia and trpv1 expression in rats with neuropathic pain. Pain Med. 2013, 14, 276-286.
88. Bach-Rojecky, L.; Salkovic-Petrisic, M.; Lackovic, Z. Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: Bilateral effect after unilateral injection. Eur. J. Pharmacol. 2010, 633, 10-14.
89. Bach-Rojecky, L.; Lackovic, Z. Central origin of the antinociceptive action of botulinum toxin type A. Pharmacol. Biochem. Behav. 2009, 94, 234-238.
90. Shimizu, T.; Shibata, M.; Toriumi, H.; Iwashita, T.; Funakubo, M.; Sato, H.; Kuroi, T.; Ebine, T.; Koizumi, K.; Suzuki, N. Reduction of trpv1 expression in the trigeminal system by botulinum neurotoxin type-A. Neurobiol. Dis. 2012, 48, 367-378.
91. Gazerani, P.; Au, S.; Dong, X.; Kumar, U.; Arendt-Nielsen, L.; Cairns, B.E. Botulinum neurotoxin type A (BoNTA) decreases the mechanical sensitivity of nociceptors and inhibits neurogenic vasodilation in a craniofacial muscle targeted for migraine prophylaxis. Pain 2010, 151, 606-616.
92. Meng, J.; Wang, J.; Lawrence, G.; Dolly, J.O. Synaptobrevin i mediates exocytosis of cgrp from sensory neurons and inhibition by botulinum toxins reflects their anti-nociceptive potential. J. Cell Sci. 2007, 120, 2864-2874.
93. Dolly, J.O.; O'Connell, M.A. Neurotherapeutics to inhibit exocytosis from sensory neurons for the control of chronic pain. Curr. Opin. Pharmacol. 2012, 12, 100-108.
94. Durham, P.L.; Cady, R. Regulation of calcitonin gene-related peptide secretion from trigeminal nerve cells by botulinum toxin type A: Implications for migraine therapy. Headache 2004, 44, 35-42; discussion 42-43.
95. Edvinsson, J.; Warfvinge, K.; Edvinsson, L. Modulation of inflammatory mediators in the trigeminal ganglion by botulinum neurotoxin type A: An organ culture study. J. Headache Pain 2015, 16, 555.
96. Silva, L.B.; Poulsen, J.N.; Arendt-Nielsen, L.; Gazerani, P. Botulinum neurotoxin type a modulates vesicular release of glutamate from satellite glial cells. J. Cell Mol. Med. 2015, 19, 1900-1909.
97. Willis, W.D., Jr. The somatosensory system, with emphasis on structures important for pain. Brain Res. Rev. 2007, 55, 297-313.
98. Bach-Rojecky, L.; Relja, M.; Lackovic, Z. Botulinum toxin type A in experimental neuropathic pain. J. Neural Transm. 2005, 112, 215-219.
99. Hoffman, R.O.; Helveston, E.M. Botulinum in the treatment of adult motility disorders. Int. Ophthalmol. Clin. 1986, 26, 241-250.
100. Ji, R.R.; Xu, Z.Z.; Gao, Y.J. Emerging targets in neuroinflammation-driven chronic pain. Nat. Rev. Drug Discov. 2014, 13, 533-548.
101. Yaksh, T.; Woller, S.; Ramachandran, R.; Sorkin, L. The search for novel analgesics: Targets and mechanisms. F1000 Biol. Rep. 2015, in press.
102. Smith, J.A.; Davis, C.L.; Burgess, G.M. Prostaglandin E2-induced sensitization of bradykinin-evoked responses in rat dorsal root ganglion neurons is mediated by cAMP-dependent protein kinase A. Eur. J. Neurosci. 2000, 12, 3250-3258.
103. Ma, W.; Quirion, R. Inflammatory mediators modulating the transient receptor potential vanilloid 1 receptor: Therapeutic targets to treat inflammatory and neuropathic pain. Expert Opin. Ther. Targets 2007, 11, 307-320.
104. Chahine, M.; O'Leary, M.E. Regulation/modulation of sensory neuron sodium channels. Handb. Exp. Pharmacol. 2014, 221, 111-135.
105. Gold, M.S.; Levine, J.D.; Correa, A.M. Modulation of TTX-R ina by PKC and PKA and their role in PGE2-induced sensitization of rat sensory neurons in vitro. J. Neurosci. Off. J. Soc. Neurosci. 1998, 18, 10345-10355.
106. Aley, K.O.; Levine, J.D. Role of protein kinase A in the maintenance of inflammatory pain. J. Neurosci. 1999, 19, 2181-2186.
107. Waxman, S.G.; Cummins, T.R.; Dib-Hajj, S.D.; Black, J.A. Voltage-gated sodium channels and the molecular pathogenesis of pain: A review. J. Rehabil. Res. Dev. 2000, 37, 517-528.
108. Suzuki, R.; Dickenson, A. Spinal and supraspinal contributions to central sensitization in peripheral neuropathy. Neuro-Signals 2005, 14, 175-181.
109. Ji, R.R.; Kawasaki, Y.; Zhuang, Z.Y.; Wen, Y.R.; Zhang, Y.Q. Protein kinases as potential targets for the treatment of pathological pain. Handb. Exp. Pharmacol. 2007, 177, 359-389.
110. Crown, E.D. The role of mitogen activated protein kinase signaling in microglia and neurons in the initiation and maintenance of chronic pain. Exp. Neurol. 2012, 234, 330-339.
111. Edelmayer, R.M.; Brederson, J.D.; Jarvis, M.F.; Bitner, R.S. Biochemical and pharmacological assessment of map-kinase signaling along pain pathways in experimental rodent models: A potential tool for the discovery of novel antinociceptive therapeutics. Biochem. Pharmacol. 2014, 87, 390-398.
112. Choi, J.I.; Svensson, C.I.; Koehrn, F.J.; Bhuskute, A.; Sorkin, L.S. Peripheral inflammation induces tumor necrosis factor dependent ampa receptor trafficking and akt phosphorylation in spinal cord in addition to pain behavior. Pain 2010, 149, 243-253.
113. Ma, W.; Quirion, R. Targeting cell surface trafficking of pain-facilitating receptors to treat chronic pain conditions. Expert Opin. Ther. Targets 2014, 18, 459-472.
114. Kopach, O.; Krotov, V.; Belan, P.; Voitenko, N. Inflammatory-induced changes in synaptic drive and postsynaptic ampars in lamina ii dorsal horn neurons are cell-type specific. Pain 2015, 156, 428-438.
115. Taves, S.; Berta, T.; Chen, G.; Ji, R.R. Microglia and spinal cord synaptic plasticity in persistent pain. Neural Plast. 2013, 2013, 753656.
116. Sofroniew, M.V. Multiple roles for astrocytes as effectors of cytokines and inflammatory mediators. Neurosci. Rev. J. Bringing Neurobiol. Neurol. Psychiatry 2014, 20, 160-172.
117. Ramachandran, R.; Yaksh, T.L. Therapeutic use of botulinum toxin in migraine: Mechanisms of action. Br. J. Pharmacol. 2014, 171, 4177-4192.
118. Christianson, C.A.; Corr, M.; Firestein, G.S.; Mobargha, A.; Yaksh, T.L.; Svensson, C.I. Characterization of the acute and persistent pain state present in K/BxN serum transfer arthritis. Pain 2010, 151, 394-403.
119. Bas, D.B.; Su, J.; Sandor, K.; Agalave, N.M.; Lundberg, J.; Codeluppi, S.; Baharpoor, A.; Nandakumar, K.S.; Holmdahl, R.; Svensson, C.I. Collagen antibody-induced arthritis evokes persistent pain with spinal glial involvement and transient prostaglandin dependency. Arthritis Rheum. 2012, 64, 3886-3896.
120. Jimenez-Andrade, J.M.; Mantyh, P.W. Sensory and sympathetic nerve fibers undergo sprouting and neuroma formation in the painful arthritic joint of geriatric mice. Arthritis Res. Therapy 2012, 14, R101.
121. Xu, Q.; Yaksh, T.L. A brief comparison of the pathophysiology of inflammatory versus neuropathic pain. Curr. Opin. Anaesthesiol. 2011, 24, 400-407.
122. Taylor, P.; Manger, B.; Alvaro-Gracia, J.; Johnstone, R.; Gomez-Reino, J.; Eberhardt, E.; Wolfe, F.; Schwartzman, S.; Furfaro, N.; Kavanaugh, A. Patient perceptions concerning pain management in the treatment of rheumatoid arthritis. J. Int. Med. Res. 2010, 38, 1213-1224.
123. Wolfe, F.; Michaud, K. Assessment of pain in rheumatoid arthritis: Minimal clinically significant difference, predictors, and the effect of anti-tumor necrosis factor therapy. J. Rheumatol. 2007, 34, 1674-1683.
124. DePuy, T.; Howard, R.; Keegan, K.; Wilson, D.; Kramer, J.; Cook, J.L.; Childers, M.K. Effects of intra-articular botulinum toxin type A in an equine model of acute synovitis: A pilot study. Am. J. Phys. Med. Rehabil./Assoc. Acad. Physiatr. 2007, 86, 777-783.
125. Akaike, N.; Shin, M.C.; Wakita, M.; Torii, Y.; Harakawa, T.; Ginnaga, A.; Kato, K.; Kaji, R.; Kozaki, S. Transsynaptic inhibition of spinal transmission by A2 botulinum toxin. J. Physiol. 2013, 591, 1031-1043.
126. Mazzocchio, R.; Caleo, M. More than at the neuromuscular synapse: Actions of botulinum neurotoxin A in the central nervous system. Neurosci. Rev. J. Bringing Neurobiol. Neurol. Psychiatry 2015, 21, 44-61.
127. Gerwin, R. Botulinum toxin treatment of myofascial pain: A critical review of the literature. Curr. Pain Headache Rep. 2012, 16, 413-422.
128. Avendano-Coy, J.; Gomez-Soriano, J.; Valencia, M.; Estrada, J.; Leal, F.; Ruiz-Campa, R. Botulinum toxin type A and myofascial pain syndrome: A retrospective study of 301 patients. J. Back Musculoskelet. Rehabil. 2014, 27, 485-492.
129. Zhou, J.Y.; Wang, D. An update on botulinum toxin A injections of trigger points for myofascial pain. Curr. Pain Headache Rep. 2014, 18, 386.
130. Desai, M.J.; Shkolnikova, T.; Nava, A.; Inwald, D. A critical appraisal of the evidence for botulinum toxin type A in the treatment for cervico-thoracic myofascial pain syndrome. Pain Pract. Off. J. World Inst. Pain 2014, 14, 185-195.
131. Singh, J.A.; Mahowald, M.L.; Kushnaryov, A.; Goelz, E.; Dykstra, D. Repeat injections of intra-articular botulinum toxin A for the treatment of chronic arthritis joint pain. J. Clin. Rheumatol. Pract. Rep. Rheum. Musculoskelet. Dis. 2009, 15, 35-38.
132. Kramer, H.H.; Angerer, C.; Erbguth, F.; Schmelz, M.; Birklein, F. Botulinum toxin A reduces neurogenic flare but has almost no effect on pain and hyperalgesia in human skin. J. Neurol. 2003, 250, 188-193.
133. Sorkin, L.S.; Yaksh, T.L. Behavioral models of pain states evoked by physical injury to the peripheral nerve. NeuroTherapeutics 2009, 6, 609-619.
134. Challa, S.R. Surgical animal models of neuropathic pain: Pros and Cons. Int. J. Neurosci. 2015, 125, 170-174.
135. Siau, C.; Xiao, W.; Bennett, G.J. Paclitaxel-and vincristine-evoked painful peripheral neuropathies: Loss of epidermal innervation and activation of langerhans cells. Exp. Neurol. 2006, 201, 507-514.
136. Tesch, G.H.; Allen, T.J. Rodent models of streptozotocin-induced diabetic nephropathy. Nephrology 2007, 12, 261-266.
137. Devor, M. Sodium channels and mechanisms of neuropathic pain. J. Pain. 2006, 7, S3-S12.
138. Amir, R.; Devor, M. Extra spike formation in sensory neurons and the disruption of afferent spike patterning. Biophys. J. 2003, 84, 2700-2708.
139. Tsujino, H.; Kondo, E.; Fukuoka, T.; Dai, Y.; Tokunaga, A.; Miki, K.; Yonenobu, K.; Ochi, T.; Noguchi, K. Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury. Mol. Cell. Neurosci. 2000, 15, 170-182.
140. Strickland, I.T.; Martindale, J.C.; Woodhams, P.L.; Reeve, A.J.; Chessell, I.P.; McQueen, D.S. Changes in the expression of NaV1.7, NaV1.8 and NaV1.9 in a distinct population of dorsal root ganglia innervating the rat knee joint in a model of chronic inflammatory joint pain. Eur. J. Pain 2008, 12, 564-572.
141. Chien, L.Y.; Cheng, J.K.; Chu, D.; Cheng, C.F.; Tsaur, M.L. Reduced expression of a-type potassium channels in primary sensory neurons induces mechanical hypersensitivity. J. Neurosci. 2007, 27, 9855-9865.
142. Burnstock, G.; Krugel, U.; Abbracchio, M.P.; Illes, P. Purinergic signalling: From normal behaviour to pathological brain function. Prog. Neurobiol. 2011, 95, 229-274.
143. Chang, Y.W.; Winkelstein, B.A. Schwann cell proliferation and macrophage infiltration are evident at day 14 after painful cervical nerve root compression in the rat. J. Neurotrauma 2011, 28, 2429-2438.
144. Abbadie, C.; Lindia, J.A.; Cumiskey, A.M.; Peterson, L.B.; Mudgett, J.S.; Bayne, E.K.; DeMartino, J.A.; MacIntyre, D.E.; Forrest, M.J. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc. Natl. Acad Sci. USA 2003, 100, 7947-7952.
145. Tofaris, G.K.; Patterson, P.H.; Jessen, K.R.; Mirsky, R. Denervated schwann cells attract macrophages by secretion of leukemia inhibitory factor (LIF) and monocyte chemoattractant protein-1 in a process regulated by interleukin-6 and LIF. J. Neurosci. 2002, 22, 6696-6703.
146. McLachlan, E.M.; Hu, P. Inflammation in dorsal root ganglia after peripheral nerve injury: Effects of the sympathetic innervation. Auton. Neurosci. Basic Clin. 2014, 182, 108-117.
147. Blum, E.; Procacci, P.; Conte, V.; Hanani, M. Systemic inflammation alters satellite glial cell function and structure. A possible contribution to pain. Neuroscience 2014, 274, 209-217.
148. Ma, C.; Shu, Y.; Zheng, Z.; Chen, Y.; Yao, H.; Greenquist, K.W.; White, F.A.; LaMotte, R.H. Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons. J. Neurophysiol. 2003, 89, 1588-1602.
149. Huang, L.Y.; Gu, Y.; Chen, Y. Communication between neuronal somata and satellite glial cells in sensory ganglia. Glia 2013, 61, 1571-1581.
150. Sukhotinsky, I.; Ben-Dor, E.; Raber, P.; Devor, M. Key role of the dorsal root ganglion in neuropathic tactile hypersensibility. Eur. J. Pain 2004, 8, 135-143.
151. Ellis, A.; Bennett, D.L. Neuroinflammation and the generation of neuropathic pain. Br. J. Anaesth. 2013, 111, 26-37.
152. Ji, R.R.; Berta, T.; Nedergaard, M. Glia and pain: Is chronic pain a gliopathy? Pain 2013, 154 (Suppl. 1), S10-S28.
153. Gobel, H.; Heinze, A.; Heinze-Kuhn, K.; Jost, W.H. Evidence-based medicine: Botulinum toxin A in migraine and tension-type headache. J. Neurol. 2001, 248 (Suppl. 1), 34-38.
154. Wheeler, A.; Smith, H.S. Botulinum toxins: Mechanisms of action, antinociception and clinical applications. Toxicology 2013, 306, 124-146.
155. Quick, M.W. The role of snare proteins in trafficking and function of neurotransmitter transporters. Handb. Exp. Pharmacol. 2006, 181-196.
156. Schrattenholz, A.; Soskic, V. Nmda receptors are not alone: Dynamic regulation of nmda receptor structure and function by neuregulins and transient cholesterol-rich membrane domains leads to disease-specific nuances of glutamate-signalling. Curr. Top. Med. Chem. 2006, 6, 663-686.
157. Hou, Q.; Huang, Y.; Amato, S.; Snyder, S.H.; Huganir, R.L.; Man, H.Y. Regulation of ampa receptor localization in lipid rafts. Mol. Cell. Neurosci. 2008, 38, 213-223.
158. Patel, H.H.; Murray, F.; Insel, P.A. G-protein-coupled receptor-signaling components in membrane raft and caveolae microdomains. Handb. Exp. Pharmacol. 2008, 167-184.
159. Delint-Ramirez, I.; Fernandez, E.; Bayes, A.; Kicsi, E.; Komiyama, N.H.; Grant, S.G. In vivo composition of nmda receptor signaling complexes differs between membrane subdomains and is modulated by PSD-95 and PSD-93. J. Neurosci. 2010, 30, 8162-8170.
160. Fessler, M.B.; Parks, J.S. Intracellular lipid flux and membrane microdomains as organizing principles in inflammatory cell signaling. J. Immunol. 2011, 187, 1529-1535.
161. Kakegawa, W.; Yuzaki, M. A mechanism underlying ampa receptor trafficking during cerebellar long-term potentiation. Proc. Natl. Acad. Sci. USA 2005, 102, 17846-17851.
162. Verderio, C.; Pozzi, D.; Pravettoni, E.; Inverardi, F.; Schenk, U.; Coco, S.; Proux-Gillardeaux, V.; Galli, T.; Rossetto, O.; Frassoni, C.; et al. Snap-25 modulation of calcium dynamics underlies differences in gabaergic and glutamatergic responsiveness to depolarization. Neuron 2004, 41, 599-610.
163. Pozzi, D.; Condliffe, S.; Bozzi, Y.; Chikhladze, M.; Grumelli, C.; Proux-Gillardeaux, V.; Takahashi, M.; Franceschetti, S.; Verderio, C.; Matteoli, M. Activity-dependent phosphorylation of SER187 is required for snap-25-negative modulation of neuronal voltage-gated calcium channels. Proc. Natl. Acad. Sci. USA 2008, 105, 323-328.
164. Gerachshenko, T.; Blackmer, T.; Yoon, E.J.; Bartleson, C.; Hamm, H.E.; Alford, S. Gbetagamma acts at the C terminus of SNAP-25 to mediate presynaptic inhibition. Nat. Neurosci. 2005, 8, 597-605.
165. Morenilla-Palao, C.; Planells-Cases, R.; García-Sanz, N.; Ferrer-Montiel, A. Regulated exocytosis contributes to protein kinase C potentiation of vanilloid receptor activity. J. Biol. Chem. 2004, 279, 25665-25672.
166. Pellett, S. Progress in cell based assays for botulinum neurotoxin detection. Curr. Top. Microbiol. Immunol. 2013, 364, 257-285.
167. Richardson, J.D.; Vasko, M.R. Cellular mechanisms of neurogenic inflammation. J. Pharmacol. Exp. Ther. 2002, 302, 839-845.
168. Woolf, C.J.; Ma, Q. Nociceptors-noxious stimulus detectors. Neuron 2007, 55, 353-364.
169. Hucho, T.; Levine, J.D. Signaling pathways in sensitization: Toward a nociceptor cell biology. Neuron 2007, 55, 365-376.
170. Ernst, J.D. Bacterial inhibition of phagocytosis. Cell. Microbiol. 2000, 2, 379-386.
171. Mollinedo, F.; Calafat, J.; Janssen, H.; Martin-Martin, B.; Canchado, J.; Nabokina, S.M.; Gajate, C. Combinatorial snare complexes modulate the secretion of cytoplasmic granules in human neutrophils. J. Immunol. 2006, 177, 2831-2841.
172. Murray, R.Z.; Stow, J.L. Cytokine secretion in macrophages: Snares, rabs, and membrane trafficking. Front. Immunol. 2014, 5, 538.
173. Tecchio, C.; Micheletti, A.; Cassatella, M.A. Neutrophil-derived cytokines: Facts beyond expression. Front. Immunol. 2014, 5, 508.
174. Sheshachalam, A.; Srivastava, N.; Mitchell, T.; Lacy, P.; Eitzen, G. Granule protein processing and regulated secretion in neutrophils. Front. Immunol. 2014, 5, 448.
175. Moon, T.C.; Befus, A.D.; Kulka, M. Mast cell mediators: Their differential release and the secretory pathways involved. Front. Immunol. 2014, 5, 569.
176. Logan, M.R.; Odemuyiwa, S.O.; Moqbel, R. Understanding exocytosis in immune and inflammatory cells: The molecular basis of mediator secretion. J. Allergyd Clin. Immunol. 2003, 111, 923-932; quiz 933.
177. Lorentz, A.; Baumann, A.; Vitte, J.; Blank, U. The snare machinery in mast cell secretion. Front. Immunol. 2012, 3, 143.
178. Park, T.H. The effects of botulinum toxin A on mast cell activity: Preliminary results. Burns J. Int. Soc. Burn Inj. 2013, 39, 816-817.
179. Akhtar, N.; Brooks, P. The use of botulinum toxin in the management of burns itching: Preliminary results. Burns 2012, 38, 1119-1123.
180. Burstein, R.; Yamamura, H.; Malick, A.; Strassman, A.M. Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J. Neurophysiol. 1998, 79, 964-982.
181. Burstein, R.; Zhang, X.; Levy, D.; Aoki, K.R.; Brin, M.F. Selective inhibition of meningeal nociceptors by botulinum neurotoxin type A: Therapeutic implications for migraine and other pains. Cephalalgia Int. J. Headache 2014, 34, 853-869.
182. Salaun, C.; Gould, G.W.; Chamberlain, L.H. Lipid raft association of snare proteins regulates exocytosis in PC12 cells. J. Biol. Chem. 2005, 280, 19449-19453.
183. Owen, D.M.; Magenau, A.; Williamson, D.; Gaus, K. The lipid raft hypothesis revisited-New insights on raft composition and function from super-resolution fluorescence microscopy. BioEssays 2012, 34, 739-747.
184. Meng, J.; Ovsepian, S.V.; Wang, J.; Pickering, M.; Sasse, A.; Aoki, K.R.; Lawrence, G.W.; Dolly, J.O. 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. 2009, 29, 4981-4992.
185. Montell, C. Exciting trips for TRPS. Nat. Cell Biol. 2004, 6, 690-692.
186. Lan, J.Y.; Skeberdis, V.A.; Jover, T.; Grooms, S.Y.; Lin, Y.; Araneda, R.C.; Zheng, X.; Bennett, M.V.; Zukin, R.S. Protein kinase C modulates nmda receptor trafficking and gating. Nat. Neurosci. 2001, 4, 382-390.
187. Planells-Cases, R.; Ferrer-Montiel, A. TRP Channel Trafficking. In TRP Ion Channel Function in Sensory Transduction and Cellular Signaling Cascades ; Liedtke, W.B., Heller, S., Eds.; CRC Press: Boca Raton, FL, USA, 2007; Chapter 23.
188. Ferrandiz-Huertas, C.; Mathivanan, S.; Wolf, C.J.; Devesa, I.; Ferrer-Montiel, A. Trafficking of thermotrp channels. Membranes 2014, 4, 525-564.
189. Yaksh, T.L.; Ozaki, G.; McCumber, D.; Rathbun, M.; Svensson, C.; Malkmus, S.; Yaksh, M.C. An automated flinch detecting system for use in the formalin nociceptive bioassay. J. Appl. Physiol. 2001, 90, 2386-2402.
190. Antonucci, F.; Rossi, C.; Gianfranceschi, L.; Rossetto, O.; Caleo, M. Long-distance retrograde effects of botulinum neurotoxin A. J. Neurosci. 2008, 28, 3689-3696.
191. Restani, L.; Antonucci, F.; Gianfranceschi, L.; Rossi, C.; Rossetto, O.; Caleo, M. Evidence for anterograde transport and transcytosis of botulinum neurotoxin A (BoNT/A). J. Neurosci. 2011, 31, 15650-15659.
192. Restani, L.; Giribaldi, F.; Manich, M.; Bercsenyi, K.; Menendez, G.; Rossetto, O.; Caleo, M.; Schiavo, G. Botulinum neurotoxins A and e undergo retrograde axonal transport in primary motor neurons. PLoS Pathog. 2012, 8, e1003087.
193. Lawrence, G.W.; Ovsepian, S.V.; Wang, J.; Aoki, K.R.; Dolly, J.O. Extravesicular intraneuronal migration of internalized botulinum neurotoxins without detectable inhibition of distal neurotransmission. Biochem. J. 2012, 441, 443-452.
194. Habermann, E. 125I-labeled neurotoxin from clostridium botulinum a: Preparation, binding to synaptosomes and ascent to the spinal cord. Naunyn-Schmiedeberg's Arch. Pharmacol. 1974, 281, 47-56.
195. Wiegand, H.; Erdmann, G.; Wellhoner, H.H. 125I-labelled botulinum A neurotoxin: Pharmacokinetics in cats after intramuscular injection. Naunyn-Schmiedeberg's Arch. Pharmacol. 1976, 292, 161-165.
196. Black, J.D.; Dolly, J.O. 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. 1986, 103, 521-534.
197. Matak, I.; Riederer, P.; Lackovic, Z. Botulinum toxin's axonal transport from periphery to the spinal cord. Neurochem. Int. 2012, 61, 236-239.
198. Aoki, K.R. Evidence for antinociceptive activity of botulinum toxin type A in pain management. Headache 2003, 43 (Suppl. 1), S9-S15.
199. Koizumi, H.; Goto, S.; Okita, S.; Morigaki, R.; Akaike, N.; Torii, Y.; Harakawa, T.; Ginnaga, A.; Kaji, R. Spinal central effects of peripherally applied botulinum neurotoxin A in comparison between its subtypes A1 and A2. Front. Neurol. 2014, 5, 98.
200. Restani, L.; Novelli, E.; Bottari, D.; Leone, P.; Barone, I.; Galli-Resta, L.; Strettoi, E.; Caleo, M. Botulinum neurotoxin A impairs neurotransmission following retrograde transynaptic transport. Traffic 2012, 13, 1083-1089.
201. Alexiades-Armenakas, M. Retrograde transport and transcytosis of botulinum toxin serotypes to the brain: Analysis of potential neurotoxicity. J. Drugs Dermatol. JDD 2008, 7, 1006-1007.
202. Marchand-Pauvert, V.; Aymard, C.; Giboin, L.S.; Dominici, F.; Rossi, A.; Mazzocchio, R. Beyond muscular effects: Depression of spinal recurrent inhibition after botulinum neurotoxin A. J. Physiol. 2013, 591, 1017-1029.
203. Takasusuki, T.; Yaksh, T.L. The effects of intrathecal and systemic gabapentin on spinal substance p release. Anesth. Analg. 2011, 112, 971-976.
204. Yaksh, T.L. Calcium channels as therapeutic targets in neuropathic pain. J. Pain 2006, 7, S13-30.
205. Malmberg, A.B.; Yaksh, T.L. Effect of continuous intrathecal infusion of omega-conopeptides, n-type calcium-channel blockers, on behavior and antinociception in the formalin and hot-plate tests in rats. Pain 1995, 60, 83-90.
206. Adams, D.J.; Callaghan, B.; Berecki, G. Analgesic conotoxins: Block and G protein-coupled receptor modulation of N-type (CaV 2.2) calcium channels. Br. J. Pharmacol. 2012, 166, 486-500.
207. Terashima, T.; Xu, Q.; Yamaguchi, S.; Yaksh, T.L. Intrathecal P/Q-and R-type calcium channel blockade of spinal substance P release and c-Fos expression. Neuropharmacology 2013, 75, 1-8.
208. Chaplan, S.R.; Bach, F.W.; Pogrel, J.W.; Chung, J.M.; Yaksh, T.L. Quantitative assessment of tactile allodynia in the rat paw. J. Neurosci. Methods 1994, 53, 55-63.
209. Chaplan, S.R.; Pogrel, J.W.; Yaksh, T.L. Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia. J. Pharmacol. Exp. Ther. 1994, 269, 1117-1123.
210. Xiao, Y.; Richter, J.A.; Hurley, J.H. Release of glutamate and cgrp from trigeminal ganglion neurons: Role of calcium channels and 5-ht1 receptor signaling. Mol. Pain 2008, 4, 12.
211. Gu, J.G.; MacDermott, A.B. Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature 1997, 389, 749-753.
212. Nguyen, D.; Deng, P.; Matthews, E.A.; Kim, D.S.; Feng, G.; Dickenson, A.H.; Xu, Z.C.; Luo, Z.D. 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 2009, 5, 6.
213. Shinder, V.; Amir, R.; Devor, M. Cross-excitation in dorsal root ganglia does not depend on close cell-to-cell apposition. Neuroreport 1998, 9, 3997-4000.
214. Devor, M.; Wall, P.D. Cross-excitation in dorsal root ganglia of nerve-injured and intact rats. J. Neurophysiol. 1990, 64, 1733-1746.
215. Amir, R.; Devor, M. Functional cross-excitation between afferent a-and c-neurons in dorsal root ganglia. Neuroscience 2000, 95, 189-195.
216. Kung, L.H.; Gong, K.; Adedoyin, M.; Ng, J.; Bhargava, A.; Ohara, P.T.; Jasmin, L. Evidence for glutamate as a neuroglial transmitter within sensory ganglia. PLoS ONE 2013, 8, e68312.
217. Ferrari, L.F.; Lotufo, C.M.; Araldi, D.; Rodrigues, M.A.; Macedo, L.P.; Ferreira, S.H.; Parada, C.A. Inflammatory sensitization of nociceptors depends on activation of nmda receptors in drg satellite cells. Proc. Natl. Acad. Sci. USA 2014, 111, 18363-18368.
218. Omoto, K.; Maruhama, K.; Terayama, R.; Yamamoto, Y.; Matsushita, O.; Sugimoto, T.; Oguma, K.; Matsuka, Y. Cross-excitation in peripheral sensory ganglia associated with pain transmission. Toxins 2015, 7, 2906-2917.
219. Steinberg, J.P.; Huganir, R.L.; Linden, D.J. N-ethylmaleimide-sensitive factor is required for the synaptic incorporation and removal of ampa receptors during cerebellar long-term depression. Proc. Natl. Acad. Sci. USA 2004, 101, 18212-18216.
220. Lau, C.G.; Takayasu, Y.; Rodenas-Ruano, A.; Paternain, A.V.; Lerma, J.; Bennett, M.V.; Zukin, R.S. SNAP-25 is a target of protein kinase C phosphorylation critical to NMDA receptor trafficking. J. Neurosci. 2010, 30, 242-254.
221. Larsson, M.; Broman, J. Synaptic plasticity and pain: Role of ionotropic glutamate receptors. Neuroscientist 2011, 17, 256-273.
222. Bardoni, R. Role of presynaptic glutamate receptors in pain transmission at the spinal cord level. Curr. Neuropharmacol. 2013, 11, 477-483.
223. Walker, S.M.; Beggs, S.; Baccei, M.L. Persistent changes in peripheral and spinal nociceptive processing after early tissue injury. Exp. Neurol. 2015, doi:10.1016/j.expneurol.2015.06.020.
224. Huang, P.P.; Khan, I.; Suhail, M.S.; Malkmus, S.; Yaksh, T.L. Spinal botulinum neurotoxin B: Effects on afferent transmitter release and nociceptive processing. PLoS ONE 2011, 6, e19126.
225. Lee, W.H.; Shin, T.J.; Kim, H.J.; Lee, J.K.; Suh, H.W.; Lee, S.C.; Seo, K. Intrathecal administration of botulinum neurotoxin type A attenuates formalin-induced nociceptive responses in mice. Anesth. Analg. 2011, 112, 228-235.
226. Coelho, A.; Oliveira, R.; Rossetto, O.; Cruz, C.D.; Cruz, F.; Avelino, A. Intrathecal administration of botulinum toxin type A improves urinary bladder function and reduces pain in rats with cystitis. Eur. J. Pain 2014, 18, 1480-1489.
227. Schiavo, G.; Benfenati, F.; Poulain, B.; Rossetto, O.; Polverino de Laureto, P.; DasGupta, B.R.; Montecucco, C. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 1992, 359, 832-835.
228. Verderio, C.; Grumelli, C.; Raiteri, L.; Coco, S.; Paluzzi, S.; Caccin, P.; Rossetto, O.; Bonanno, G.; Montecucco, C.; Matteoli, M. Traffic of botulinum toxins A and e in excitatory and inhibitory neurons. Traffic 2007, 8, 142-153.
229. Dolly, J.O.; Lawrence, G.W.; Meng, J.; Wang, J.; Ovsepian, S.V. Neuro-exocytosis: Botulinum toxins as inhibitory probes and versatile therapeutics. Curr. Opin. Pharmacol. 2009, 9, 326-335.
230. Habermann, E. Inhibition by tetanus and botulinum A toxin of the release of [3H]noradrenaline and [3H]gaba from rat brain homogenate. Experientia 1988, 44, 224-226.
231. Carroll, I.; Fischbein, N.; Barad, M.; Mackey, S. Human response to unintended intrathecal injection of botulinum toxin. Pain Med. 2011, 12, 1094-1097.
232. Marinelli, S.; Vacca, V.; Ricordy, R.; Uggenti, C.; Tata, A.M.; Luvisetto, S.; Pavone, F. The analgesic effect on neuropathic pain of retrogradely transported botulinum neurotoxin a involves schwann cells and astrocytes. PLoS ONE 2012, 7, e47977.
233. Littlewood, N.K.; Todd, A.J.; Spike, R.C.; Watt, C.; Shehab, S.A. The types of neuron in spinal dorsal horn which possess neurokinin-1 receptors. Neuroscience 1995, 66, 597-608.
234. Scholz, J.; Woolf, C.J. The neuropathic pain triad: Neurons, immune cells and glia. Nat. Neurosci. 2007, 10, 1361-1368.
235. Peng, H.; Kang, N.; Xu, J.; Stanton, P.K.; Kang, J. Two distinct modes of exocytotic fusion pore expansion in large astrocytic vesicles. J. Biol. Chem. 2013, 288, 16872-16881.
236. Verderio, C.; Cagnoli, C.; Bergami, M.; Francolini, M.; Schenk, U.; Colombo, A.; Riganti, L.; Frassoni, C.; Zuccaro, E.; Danglot, L.; et al. Ti-VAMP/VAMP7 is the snare of secretory lysosomes contributing to ATP secretion from astrocytes. Biol. Cell 2012, 104, 213-228.
237. Prada, I.; Marchaland, J.; Podini, P.; Magrassi, L.; D'Alessandro, R.; Bezzi, P.; Meldolesi, J. REST/NRSF governs the expression of dense-core vesicle gliosecretion in astrocytes. J. Cell Biol. 2011, 193, 537-549.
238. Hepp, R.; Perraut, M.; Chasserot-Golaz, S.; Galli, T.; Aunis, D.; Langley, K.; Grant, N.J. Cultured glial cells express the SNAP-25 analogue SNAP-23. Glia 1999, 27, 181-187.
239. Parpura, V.; Fang, Y.; Basarsky, T.; Jahn, R.; Haydon, P.G. Expression of synaptobrevin II, cellubrevin and syntaxin but not SNAP-25 in cultured astrocytes. FEBS Lett. 1995, 377, 489-492.
240. Schubert, V.; Bouvier, D.; Volterra, A. Snare protein expression in synaptic terminals and astrocytes in the adult hippocampus: A comparative analysis. Glia 2011, 59, 1472-1488.
241. Jeftinija, S.D.; Jeftinija, K.V.; Stefanovic, G. Cultured astrocytes express proteins involved in vesicular glutamate release. Brain Res. 1997, 750, 41-47.
242. Maienschein, V.; Marxen, M.; Volknandt, W.; Zimmermann, H. A plethora of presynaptic proteins associated with ATP-storing organelles in cultured astrocytes. Glia 1999, 26, 233-244.
243. Kim, H.J.; Lee, G.W.; Kim, M.J.; Yang, K.Y.; Kim, S.T.; Bae, Y.C.; Ahn, D.K. Antinociceptive effects of transcytosed botulinum neurotoxin type A on trigeminal nociception in rats. Korean J. Physiol. Pharmacol. 2015, 19, 349-355.
244. Dover, N.; Barash, J.R.; Hill, K.K.; Xie, G.; Arnon, S.S. Molecular characterization of a novel botulinum neurotoxin type H gene. J. Infect. Dis. 2014, 209, 192-202.
245. Barash, J.R.; Arnon, S.S. A novel strain of clostridium botulinum that produces type B and type H botulinum toxins. J. Infect. Dis. 2014, 209, 183-191.
246. Kalb, S.R.; Baudys, J.; Raphael, B.H.; Dykes, J.K.; Luquez, C.; Maslanka, S.E.; Barr, J.R. Functional characterization of botulinum neurotoxin serotype H as a hybrid of known serotypes F and A (BoNT F/A). Anal. Chem. 2015, 87, 3911-3917.
247. Kalb, S.R.; Baudys, J.; Webb, R.P.; Wright, P.; Smith, T.J.; Smith, L.A.; Fernandez, R.; Raphael, B.H.; Maslanka, S.E.; Pirkle, J.L.; et al. Discovery of a novel enzymatic cleavage site for botulinum neurotoxin F5. FEBS Lett. 2012, 586, 109-115.
248. Rummel, A. Double receptor anchorage of botulinum neurotoxins accounts for their exquisite neurospecificity. Curr. Top. Microbiol. Immunol. 2013, 364, 61-90.
249. Dong, M.; Yeh, F.; Tepp, W.H.; Dean, C.; Johnson, E.A.; Janz, R.; Chapman, E.R. Sv2 is the protein receptor for botulinum neurotoxin a. Science 2006, 312, 592-596.
250. Jacky, B.P.; Garay, P.E.; Dupuy, J.; Nelson, J.B.; Cai, B.; Molina, Y.; Wang, J.; Steward, L.E.; Broide, R.S.; Francis, J.; et al. Identification of fibroblast growth factor receptor 3 (FGFR3) as a protein receptor for botulinum neurotoxin serotype A (BoNT/A). PLoS Pathog. 2013, 9, e1003369.
251. Grothe, C.; Meisinger, C.; Claus, P. In vivo expression and localization of the fibroblast growth factor system in the intact and lesioned rat peripheral nerve and spinal ganglia. J. Comp. Neurol. 2001, 434, 342-357.
252. Jungnickel, J.; Gransalke, K.; Timmer, M.; Grothe, C. Fibroblast growth factor receptor 3 signaling regulates injury-related effects in the peripheral nervous system. Mol. Cell. Neurosci. 2004, 25, 21-29.
253. Pringle, N.P.; Yu, W.P.; Howell, M.; Colvin, J.S.; Ornitz, D.M.; Richardson, W.D. FGFR3 expression by astrocytes and their precursors: Evidence that astrocytes and oligodendrocytes originate in distinct neuroepithelial domains. Development 2003, 130, 93-102.
254. Niidome, T.; Nonaka, H.; Akaike, A.; Kihara, T.; Sugimoto, H. Basic fibroblast growth factor promotes the generation of microtubule-associated protein 2-positive cells from microglia. Biochem. Biophys. Res. Commun. 2009, 390, 1018-1022.
255. Peng, L.; Adler, M.; Demogines, A.; Borrell, A.; Liu, H.; Tao, L.; Tepp, W.H.; Zhang, S.C.; Johnson, E.A.; Sawyer, S.L.; et al. Widespread sequence variations in vamp1 across vertebrates suggest a potential selective pressure from botulinum neurotoxins. PLoS Pathog. 2014, 10, e1004177.
256. Yamasaki, S.; Baumeister, A.; Binz, T.; Blasi, J.; Link, E.; Cornille, F.; Roques, B.; Fykse, E.M.; Sudhof, T.C.; Jahn, R. Cleavage of members of the synaptobrevin/VAMP family by types D and F botulinal neurotoxins and tetanus toxin. J. Biol. Chem. 1994, 269, 12764-12772.
257. Yamamoto, H.; Ida, T.; Tsutsuki, H.; Mori, M.; Matsumoto, T.; Kohda, T.; Mukamoto, M.; Goshima, N.; Kozaki, S.; Ihara, H. Specificity of botulinum protease for human vamp family proteins. Microbiol. Immunol. 2012, 56, 245-253.
258. Strotmeier, J.; Willjes, G.; Binz, T.; Rummel, A. Human synaptotagmin-ii is not a high affinity receptor for botulinum neurotoxin B and G: Increased therapeutic dosage and immunogenicity. FEBS Lett. 2012, 586, 310-313.
259. Peng, L.; Berntsson, R.P.; Tepp, W.H.; Pitkin, R.M.; Johnson, E.A.; Stenmark, P.; Dong, M. Botulinum neurotoxin D-C uses synaptotagmin I/II as receptors and human synaptotagmin II is not an effective receptor for type B, D-C, and G toxins. J. Cell Sci. 2012, 125, 3233-3242.
260. Johnson, E.A. Clostridium botulinum and clostridium tetani. In Topley and Wilson's Microbiology and Microbial Infections ; Borriello, S.P.; Murray, P.R.; Funke, G., Eds.; Hodder Arnold: London, UK, 2005; Volume 8, pp. 1035-1088.
261. Eleopra, R.; Tugnoli, V.; Quatrale, R.; Rossetto, O.; Montecucco, C. Different types of botulinum toxin in humans. Mov. Disord. 2004, 19 (Suppl. 8), S53-S59.
262. Sloop, R.R.; Cole, B.A.; Escutin, R.O. Human response to botulinum toxin injection: Type B compared with type A. Neurology 1997, 49, 189-194.
263. Foran, P.G.; Mohammed, N.; Lisk, G.O.; Nagwaney, S.; Lawrence, G.W.; Johnson, E.; Smith, L.; Aoki, K.R.; Dolly, J.O. 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. 2003, 278, 1363-1371.
264. Keller, J.E. Recovery from botulinum neurotoxin poisoning in vivo. Neuroscience 2006, 139, 629-637.
265. Eleopra, R.; Tugnoli, V.; Quatrale, R.; Rossetto, O.; Montecucco, C.; Dressler, D. Clinical use of non-A botulinum toxins: Botulinum toxin type c and botulinum toxin type F. Neurotox. Res. 2006, 9, 127-131.
266. Eleopra, R.; Tugnoli, V.; Rossetto, O.; Montecucco, C.; de Grandis, D. Botulinum neurotoxin serotype C: A novel effective botulinum toxin therapy in human. Neurosci. Lett. 1997, 224, 91-94.
267. Houser, M.K.; Sheean, G.L.; Lees, A.J. Further studies using higher doses of botulinum toxin type F for torticollis resistant to botulinum toxin type A. J. Neurol. Neurosurg. Psychiatry 1998, 64, 577-580.
268. Sheean, G.L.; Lees, A.J. Botulinum toxin F in the treatment of torticollis clinically resistant to botulinum toxin A. J. Neurol. Neurosurg. Psychiatry 1995, 59, 601-607.
269. Greene, P.E.; Fahn, S. Use of botulinum toxin type F injections to treat torticollis in patients with immunity to botulinum toxin type A. Mov. Disord. 1993, 8, 479-483.
270. Eleopra, R.; Montecucco, C.; Devigili, G.; Lettieri, C.; Rinaldo, S.; Verriello, L.; Pirazzini, M.; Caccin, P.; Rossetto, O. Botulinum neurotoxin serotype D is poorly effective in humans: An in vivo electrophysiological study. Clin. Neurophysiol. 2013, 124, 999-1004.
271. Pellett, S.; Tepp, W.H.; Scherf, J.M.; Pier, C.L.; Johnson, E.A. Activity of botulinum neurotoxin type d (strain 1873) in human neurons. Toxicon 2015, 101, 63-69.
272. Whitemarsh, R.C.; Tepp, W.H.; Bradshaw, M.; Lin, G.; Pier, C.L.; Scherf, J.M.; Johnson, E.A.; Pellett, S. Characterization of botulinum neurotoxin a subtypes 1 through 5 by investigation of activities in mice, neuronal cell cultures, and in vitro. Infect. Immun. 2013, 81, 3894-3902.
273. Wang, D.; Krilich, J.; Pellett, S.; Baudys, J.; Tepp, W.H.; Barr, J.R.; Johnson, E.A.; Kalb, S.R. Comparison of the catalytic properties of the botulinum neurotoxin subtypes A1 and A5. Biochim. Biophys. Acta 2013, 1834, 2722-2728.
274. Pier, C.L.; Chen, C.; Tepp, W.H.; Lin, G.; Janda, K.D.; Barbieri, J.T.; Pellett, S.; Johnson, E.A. Botulinum neurotoxin subtype A2 enters neuronal cells faster than subtype a1. FEBS Lett. 2011, 585, 199-206.
275. Tepp, W.H.; Lin, G.; Johnson, E.A. Purification and characterization of a novel subtype A3 botulinum neurotoxin. Appl. Environ. Microbiol. 2012, 78, 3108-3113.
276. Kull, S.; Schulz, K.M.; Weisemann, J.; Kirchner, S.; Schreiber, T.; Bollenbach, A.; Dabrowski, P.W.; Nitsche, A.; Kalb, S.R.; Dorner, M.B.; et al. Isolation and functional characterization of the novel clostridium botulinum neurotoxin A8 subtype. PLoS ONE 2015, 10, e0116381.
277. Pellett, S.; Tepp, W.H.; Whitemarsh, R.C.; Bradshaw, M.; Johnson, E.A. In vivo onset and duration of action varies for botulinum neurotoxin A subtypes 1-5. Toxicon 2015, in press.
278. Torii, Y.; Goto, Y.; Nakahira, S.; Kozaki, S.; Kaji, R.; Ginnaga, A. Comparison of systemic toxicity between botulinum toxin subtypes A1 and A2 in mice and rats. Basic Clin. Pharmacol. Toxicol. 2014, 116, 524-528.
279. Torii, Y.; Akaike, N.; Harakawa, T.; Kato, K.; Sugimoto, N.; Goto, Y.; Nakahira, S.; Kohda, T.; Kozaki, S.; Kaji, R.; et al. 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. 2011, 117, 275-285.
280. Torii, Y.; Kiyota, N.; Sugimoto, N.; Mori, Y.; Goto, Y.; Harakawa, T.; Nakahira, S.; Kaji, R.; Kozaki, S.; Ginnaga, A. Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test. Toxicon Off. J. Int. Soc. Toxinol. 2010, 57, 93-99.
281. Mukai, Y.; Shimatani, Y.; Sako, W.; Asanuma, K.; Nodera, H.; Sakamoto, T.; Izumi, Y.; Kohda, T.; Kozaki, S.; Kaji, R. Comparison between botulinum neurotoxin type A2 and type A1 by electrophysiological study in healthy individuals. Toxicon 2014, 81, 32-36.
282. Lin, G.; Tepp, W.H.; Pier, C.L.; Jacobson, M.J.; Johnson, E.A. Expression of the clostridium botulinum A2 neurotoxin gene cluster proteins and characterization of the A2 complex. Appl. Environ. Microbiol. 2010, 76, 40-47.
283. Akaike, N.; Ito, Y.; Shin, M.C.; Nonaka, K.; Torii, Y.; Harakawa, T.; Ginnaga, A.; Kozaki, S.; Kaji, R. Effects of A2 type botulinum toxin on spontaneous miniature and evoked transmitter release from the rat spinal excitatory and inhibitory synapses. Toxicon 2010, 56, 1315-1326.
284. Henkel, J.S.; Jacobson, M.; Tepp, W.; Pier, C.; Johnson, E.A.; Barbieri, J.T. Catalytic properties of botulinum neurotoxin subtypes A3 and A4 (dagger). Biochemistry 2009, 48, 2522.
285. Wang, J.; Meng, J.; Lawrence, G.W.; Zurawski, T.H.; Sasse, A.; Bodeker, M.O.; Gilmore, M.A.; Fernandez-Salas, E.; Francis, J.; Steward, L.E.; et al. Novel chimeras of botulinum neurotoxins a and e unveil contributions from the binding, translocation, and protease domains to their functional characteristics. J. Biol. Chem. 2008, 283, 16993-17002.
286. Strotmeier, J.; Mahrhold, S.; Krez, N.; Janzen, C.; Lou, J.; Marks, J.D.; Binz, T.; Rummel, A. Identification of the synaptic vesicle glycoprotein 2 receptor binding site in botulinum neurotoxin A. FEBS Lett. 2014, 588, 1087-1093.
287. Rummel, A.; Mahrhold, S.; Bigalke, H.; Binz, T. Exchange of the HCC domain mediating double receptor recognition improves the pharmacodynamic properties of botulinum neurotoxin. FEBS J. 2011, 278, 4506-4515.
288. Band, P.A.; Blais, S.; Neubert, T.A.; Cardozo, T.J.; Ichtchenko, K. Recombinant derivatives of botulinum neurotoxin A engineered for trafficking studies and neuronal delivery. Protein Expr. Purif. 2010, 71, 62-73.
289. Vessely, C.; Estey, T.; Randolph, T.W.; Henderson, I.; Cooper, J.; Nayar, R.; Braun, L.J.; Carpenter, J.F. Stability of a trivalent recombinant protein vaccine formulation against botulinum neurotoxin during storage in aqueous solution. J. Pharm. Sci. 2009, 98, 2970-2993.
290. Vazquez-Cintron, E.J.; Vakulenko, M.; Band, P.A.; Stanker, L.H.; Johnson, E.A.; Ichtchenko, K. Atoxic derivative of botulinum neurotoxin A as a prototype molecular vehicle for targeted delivery to the neuronal cytoplasm. PLoS ONE 2014, 9, e85517.
291. Pier, C.L.; Tepp, W.H.; Bradshaw, M.; Johnson, E.A.; Barbieri, J.T.; Baldwin, M.R. Recombinant holotoxoid vaccine against botulism. Infect. Immun. 2008, 76, 437-442.
292. Bradshaw, M.; Tepp, W.H.; Whitemarsh, R.C.; Pellett, S.; Johnson, E.A. Holotoxin Activity of Botulinum Neurotoxin Subtype A4 Originating from a Nontoxigenic Clostridium botulinum Expression System. Appl. Environ. Microbiol. 2014, 80, 7415-7422.
293. Chen, S.; Barbieri, J.T. Engineering botulinum neurotoxin to extend therapeutic intervention. Proc. Natl. Acad. Sci. USA 2009, 106, 9180-9184.
294. Simpson, L. The life history of a botulinum toxin molecule. Toxicon 2013, 68, 40-59.
295. Montecucco, C.; Rasotto, M.B. On botulinum neurotoxin variability. mBio 2015, 6, e02131-14.
296. Lindstrom, M.; Myllykoski, J.; Sivela, S.; Korkeala, H. Clostridium botulinum in cattle and dairy products. Crit. Rev. Food Sci. Nutr. 2010, 50, 281-304.
297. Kruger, M.; Grosse-Herrenthey, A.; Schrodl, W.; Gerlach, A.; Rodloff, A. Visceral botulism at dairy farms in schleswig holstein, germany: Prevalence of clostridium botulinum in feces of cows, in animal feeds, in feces of the farmers, and in house dust. Anaerobe 2012, 18, 221-223.
298. Galey, F.D. Botulism in the horse. Equine Pract. 2001, 17, 579-588.
299. Elad, D.; Yas-Natan, E.; Aroch, I.; Shamir, M.H.; Kleinbart, S.; Hadash, D.; Chaffer, M.; Greenberg, K.; Shlosberg, A. Natural clostridium botulinum type C toxicosis in a group of cats. J. Clin. Microbiol. 2004, 42, 5406-5408.
300. Borst, G.H.; Lambers, G.M.; Haagsma, J. Type-C botulism in dogs. Tijdschr. Diergeneeskd. 1986, 111, 1104-1105.
301. Whitemarsh, R.C.; Strathman, M.J.; Chase, L.G.; Stankewicz, C.; Tepp, W.H.; Johnson, E.A.; Pellett, S. Novel application of human neurons derived from induced pluripotent stem cells for highly sensitive botulinum neurotoxin detection. Toxicol. Sci. 2012, 126, 426-435.
302. Raptis, A.; Torrejon-Escribano, B.; Gomez de Aranda, I.; Blasi, J. Distribution of synaptobrevin/VAMP 1 and 2 in rat brain. J. Chem. Neuroanat. 2005, 30, 201-211.
303. Karalewitz, A.P.; Fu, Z.; Baldwin, M.R.; Kim, J.J.; Barbieri, J.T. Botulinum neurotoxin serotype C associates with dual ganglioside receptors to facilitate cell entry. J. Biol. Chem. 2012, 287, 40806-40816.
304. Blasi, J.; Chapman, E.R.; Yamasaki, S.; Binz, T.; Niemann, H.; Jahn, R. Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. EMBO J. 1993, 12, 4821-4828.
305. Blasi, J.; Chapman, E.R.; Link, E.; Binz, T.; Yamasaki, S.; de Camilli, P.; Sudhof, T.C.; Niemann, H.; Jahn, R. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature 1993, 365, 160-163.
306. Peng, L.; Liu, H.; Ruan, H.; Tepp, W.H.; Stoothoff, W.H.; Brown, R.H.; Johnson, E.A.; Yao, W.D.; Zhang, S.C.; Dong, M. Cytotoxicity of botulinum neurotoxins reveals a direct role of syntaxin 1 and SNAP-25 in neuron survival. Nat. Commun. 2013, 4, 1472.
307. Wang, D.; Zhang, Z.; Dong, M.; Sun, S.; Chapman, E.R.; Jackson, M.B. Syntaxin requirement for Ca2+-triggered exocytosis in neurons and endocrine cells demonstrated with an engineered neurotoxin. Biochemistry 2011, 50, 2711-2713.
308. Wiley, R.G.; Kline, R.H.T.; Vierck, C.J., Jr. Anti-nociceptive effects of selectively destroying substance P receptor-expressing dorsal horn neurons using [Sar9, Met(O2)11]-substance P-saporin: Behavioral and anatomical analyses. Neuroscience 2007, 146, 1333-1345.
309. Wiley, R.G.; Lappi, D.A. Targeted toxins in pain. Adv. Drug Deliv. Rev. 2003, 55, 1043-1054.
310. Wiley, R.G.; Lappi, D.A. Destruction of neurokinin-1 receptor expressing cells in vitro and in vivo using substance p-saporin in rats. Neurosci. Lett. 1997, 230, 97-100.
311. Wiese, A.J.; Rathbun, M.; Butt, M.T.; Malkmus, S.A.; Richter, P.J.; Osborn, K.G.; Xu, Q.; Veesart, S.L.; Steinauer, J.J.; Higgins, D.; et al. Intrathecal substance p-saporin in the dog: Distribution, safety, and spinal neurokinin-1 receptor ablation. Anesthesiology 2013, 119, 1163-1177.
312. Mantyh, P.W.; Rogers, S.D.; Honore, P.; Allen, B.J.; Ghilardi, J.R.; Li, J.; Daughters, R.S.; Lappi, D.A.; Wiley, R.G.; Simone, D.A. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance p receptor. Science 1997, 278, 275-279.
313. Choi, J.I.; Koehrn, F.J.; Sorkin, L.S. Carrageenan induced phosphorylation of akt is dependent on neurokinin-1 expressing neurons in the superficial dorsal horn. Mol. Pain 2012, 8, 4.
314. Mustafa, G.; Anderson, E.M.; Bokrand-Donatelli, Y.; Neubert, J.K.; Caudle, R.M. Anti-nociceptive effect of a conjugate of substance p and light chain of botulinum neurotoxin type A. Pain 2013, 154, 2547-2553.
315. Keith, F.; John, C. Targeted secretion inhibitors-innovative protein therapeutics. Toxins 2010, 2, 2795-2815.
316. Edwards, J.G. TRPV1 in the central nervous system: Synaptic plasticity, function, and pharmacological implications. Prog. Drug Res. 2014, 68, 77-104.
317. Duggan, M.J.; Quinn, C.P.; Chaddock, J.A.; Purkiss, J.R.; Alexander, F.C.; Doward, S.; Fooks, S.J.; Friis, L.M.; Hall, Y.H.; Kirby, E.R.; et al. 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. 2002, 277, 34846-34852.
318. Apland, J.P.; Adler, M.; Oyler, G.A. Inhibition of neurotransmitter release by peptides that mimic the n-terminal domain of SNAP-25. J. Protein Chem. 2003, 22, 147-153.
319. Park, T.Y.; Shin, M.J.; Park, S.D.; Lee, S.K. Alleviation of abnormal synaptic neurotransmitter release by cell-permeable form of the truncated SNAP-25 upon transcutaneous delivery. Neurosci. Lett. 2013, 543, 52-57.
320. Burke, G.S. The occurrence of bacillus botulinus in nature. J. Bacteriol. 1919, 4, 541-553
321. Rossetto, O.; Pirazzini, M.; Montecucco, C. Botulinum neurotoxins: Genetic, structural and mechanistic insights. Nat. Rev. Microbiol. 2014, 12, 535-549.