R findings recommend that peripherally applied BoNT-A can generate antinociceptive effects in ION-CCI model. The underlying mechanisms may be BoNT-A directly acts on the Vc by means of axonal transport, inhibits the higher expression of TRPA1, TRPV1 andReferences Bohluli B, Motamedi MH, Bagheri SC, Bayat M, Lassemi E, Navi F, Moharamnejad N (2011) Use of botulinum toxin a for drug-refractory trigeminal neuralgia: preliminary report. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 111:470 Brin MF, Fahn S, Moskowitz C, Friedman A, Shale HM, Greene PE, Blitzer A, List T, Lange D, Lovelace RE et al (1987) Localized injections of botulinum toxin for the therapy of focal dystonia and hemifacial spasm. Mov Disord 2:23754 Cui M, Khanijou S, Rubino J, Aoki KR (2004) Subcutaneous administration of botulinum toxin a reduces formalin-induced discomfort. Discomfort 107:12533 Dieleman JP, Kerklaan J, Huygen FJ, Bouma PA, Sturkenboom MC (2008) Incidence prices and treatment of neuropathic discomfort situations within the general population. Discomfort 137:68188 Ferrandiz-Huertas C, Mathivanan S, Wolf CJ, Devesa I, Ferrer-Montiel A (2014) Trafficking of thermotrp channels. Membranes 4:52564 Filipovic B, Matak I, Bach-Rojecky L, Lackovic Z (2012) 4ebp1 Inhibitors Related Products central action of peripherally applied botulinum toxin type a on discomfort and dural protein extravasation in rat model of trigeminal neuropathy. PLoS 1 7:e29803 Hall GC, Carroll D, Parry D, McQuay HJ (2006) Epidemiology and remedy of neuropathic pain: the UK major care perspective. Discomfort 122:15662 Imamura Y, Kawamoto H, Nakanishi O (1997) Characterization of heat-hyperalgesia in an experimental trigeminal neuropathy in rats. Exp Brain Res 116:9703 Katusic S, Beard CM, Bergstralh E, Kurland LT (1990) Incidence and clinical capabilities of trigeminal neuralgia, rochester, minnesota, 1945984. Ann Neurol 27:895 Kim HJ, Lee GW, Kim MJ, Yang KY, Kim ST, Bae YC, Ahn DK (2015) Antinociceptive effects of transcytosed botulinum neurotoxin variety a on trigeminal nociception in rats. PF-06426779 In Vitro Korean J Physiol Pharmacol 19:34955 Li S, Lian YJ, Chen Y, Zhang HF, Ma YQ, He CH, Wu CJ, Xie NC, Zheng YK, Zhang Y (2014) Therapeutic impact of botulinum toxin-a in 88 sufferers with trigeminal neuralgia with 14-month follow-up. J Headache Pain 15:43 Luvisetto S, Gazerani P, Cianchetti C, Pavone F (2015) Botulinum toxin variety a as a therapeutic agent against headache and related disorders. Toxins 7:3818844 Matak I, Bach-Rojecky L, Filipovic B, Lackovic Z (2011) Behavioral and immunohistochemical evidence for central antinociceptive activity of botulinum toxin a. Neuroscience 186:201Wu et al. SpringerPlus (2016) 5:Web page eight ofMatak I, Riederer P, Lackovic Z (2012) Botulinum toxin’s axonal transport from periphery to the spinal cord. Neurochem Int 61:23639 Mickle AD, Shepherd AJ, Mohapatra DP (2015) Sensory trp channels: the key transducers of nociception and pain. Prog Mol Biol Transl Sci 131:7318 Neubert JK, Mannes AJ, Keller J, Wexel M, Iadarola MJ, Caudle RM (2005) Peripheral targeting with the trigeminal ganglion through the infraorbital foramen as a therapeutic strategy. Brain Res Protoc 15:11926 Ngeow WC, Nair R (2010) Injection of botulinum toxin type a (botox) into trigger zone of trigeminal neuralgia as a suggests to control pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 109:e47 50 Oh HM, Chung ME (2015) Botulinum toxin for neuropathic pain: a evaluation of your literature. Toxins 7:3127154 Setler PE (2002) Therapeutic use of botulinum toxins: background and history. Clin J Pain 18:S119.