1. 1. Pruimboom L, Van Dam A. Chronic pain: a non-use disease. Medical hypotheses. 2007;68(3):506-11.
2. 2. Torrance N, Elliott AM, Lee AJ, Smith BH. Severe chronic pain is associated with increased 10 year mortality. A cohort record linkage study. European journal of pain. 2010;14(4):380-6.
3. 3. Reuben DB, Alvanzo AA, Ashikaga T, Bogat GA, Callahan CM, Ruffing V, et al. National Institutes of Health Pathways to Prevention workshop: The role of opioids in the treatment of chronic painthe role of opioids in the treatment of chronic pain. Annals of Internal Medicine. 2015;162(4):295-300.
4. 4. Chou R, Turner JA, Devine EB, Hansen RN, Sullivan SD, Blazina I, et al. The Effectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain: A Systematic Review for a National Institutes of Health Pathways to Prevention WorkshopEffectiveness and Risks of Long-Term Opioid Therapy for Chronic Pain. Annals of Internal Medicine. 2015;162(4):276-86.
5. 5. Hanks W, Justins D. Cancer pain: management. The Lancet. 1992;339(8800):1031-6.
6. 6. Fine PG. The evolving and important role of anesthesiology in palliative care. Anesthesia & Analgesia. 2005;100(1):183-8.
7. 7. Wootton M. Morphine is not the only analgesic in palliative care: literature review. Journal of advanced nursing. 2004;45(5):527-32.
8. 8. Haegerstam GA. Pathophysiology of bone pain: a review. Acta orthopaedica Scandinavica. 2001;72(3):308-17.
9. 9. Lewis RJ, Garcia ML. Therapeutic potential of venom peptides. Nature Reviews Drug Discovery. 2003;2(10):790-802.
10. 10. Bogin O. Venom peptides and their mimetics as potential drugs. Modulator. 2005;19(9):14-20.
11. 11. Gomes A, Bhattacharjee P, Mishra R, Biswas AK, Dasgupta SC, Giri B, et al. Anticancer potential of animal venoms and toxins. 2010.
12. 12. Kang TS, Georgieva D, Genov N, Murakami MT, Sinha M, Kumar RP, et al. Enzymatic toxins from snake venom: structural characterization and mechanism of catalysis. The FEBS journal. 2011;278(23):4544-76.
13. 13. Jungo F, Estreicher A, Bairoch A, Bougueleret L, Xenarios I. Animal toxins: how is complexity represented in databases? Toxins. 2010;2(2):262-82.
14. 14. King GF, Gentz MC, Escoubas P, Nicholson GM. A rational nomenclature for naming peptide toxins from spiders and other venomous animals. Toxicon. 2008;52(2):264-76.
15. 15. Catterall WA. Voltage-gated calcium channels. Cold Spring Harbor perspectives in biology. 2011;3(8):a003947.
16. 16. Wright CE, Angus JA. Effects of N‐, P‐and Q‐type neuronal calcium channel antagonists on mammalian peripheral neurotransmission. British journal of pharmacology. 1996;119(1):49-56.
17. 17. Takahashi T, Momiyama A. Different types of calcium channels mediate central synaptic transmission. Nature. 1993;366(6451):156.
18. 18. Regehr WG, Mintz IM. Participation of multiple calcium channel types in transmission at single climbing fiber to Purkinje cell synapses. Neuron. 1994;12(3):605-13.
19. 19. Wheeler DB, Randall A, Tsien RW. Roles of N-type and Q-type Ca2+ channels in supporting hippocampal synaptic transmission. Science. 1994;264(5155):107-11.
20. 20. Olivera BM, Miljanich GP, Ramachandran J, Adams ME. Calcium channel diversity and neurotransmitter release: the ω-conotoxins and ω-agatoxins. Annual review of biochemistry. 1994;63(1):823-67.
21. 21. Kang SJ, Liu M-G, Shi T-Y, Zhao M-G, Kaang B-K, Zhuo M. N-type voltage gated calcium channels mediate excitatory synaptic transmission in the anterior cingulate cortex of adult mice. Molecular pain. 2013;9(1):58.
22. 22. Krzemien DM, Schaller KL, Levinson SR, Caldwell JH. Immunolocalization of sodium channel isoform NaCh6 in the nervous system. Journal of Comparative Neurology. 2000;420(1):70-83.
23. 23. Caldwell JH, Schaller KL, Lasher RS, Peles E, Levinson SR. Sodium channel Nav1. 6 is localized at nodes of Ranvier, dendrites, and synapses. Proceedings of the National Academy of Sciences. 2000;97(10):5616-20.
24. 24. McCleskey EW, Gold MS. Ion channels of nociception. Annual review of physiology. 1999;61(1):835-56.
25. 25. Frank HY, Catterall WA. Overview of the voltage-gated sodium channel family. Genome biology. 2003;4(3):207.
26. 26. Payandeh J, Scheuer T, Zheng N, Catterall WA. The crystal structure of a voltage-gated sodium channel. Nature. 2011;475(7356):353-8.
27. 27. Wonnacott S. Presynaptic nicotinic ACh receptors. Trends in neurosciences. 1997;20(2):92-8.
28. 28. Wise A, Green A, Main MJ, Wilson R, Fraser N, Marshall FH. Calcium sensing properties of the GABA B receptor. Neuropharmacology. 1999;38(11):1647-56.
29. 29. Naik AK, Tandan SK, Kumar D, Dudhgaonkar SP. Nitric oxide and its modulators in chronic constriction injury-induced neuropathic pain in rats. European journal of pharmacology. 2006;530(1):59-69.
30. 30. Martínez‐Ruiz A, Lamas S. Two decades of new concepts in nitric oxide signaling: from the discovery of a gas messenger to the mediation of nonenzymatic posttranslational modifications. IUBMB life. 2009;61(2):91-8.
31. 31. Francis SH, Busch JL, Corbin JD. cGMP-dependent protein kinases and cGMP phosphodiesterases in nitric oxide and cGMP action. Pharmacological reviews. 2010;62(3):525-63.
32. 32. Cestele S, Qu Y, Rogers JC, Rochat H, Scheuer T, Catterall WA. Voltage sensor–trapping: enhanced activation of sodium channels by β-scorpion toxin bound to the S3–S4 loop in domain II. Neuron. 1998;21(4):919-31.
33. 33. Jover E, Couraud F, Rochat H. Two types of scorpion neurotoxins characterized by their binding to two separate receptor sites on rat brain synaptosomes. Biochemical and biophysical research communications. 1980;95(4):1607-14.
34. 34. Catterall WA. Neurotoxins that act on voltage-sensitive sodium channels in excitable membranes. Annual Review of Pharmacology and Toxicology. 1980;20(1):15-43.
35. 35. Rogers JC QY TT ST, Catterall WA Molecular determinants of high affinity binding of alpha-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel alpha subunit. J BiolChem. 1996;271:15950 - 62.
36. 36. Wheeler KP, Watt DD, Lazdunski M. Classification of Na channel receptors specific for various scorpion toxins. Pflügers Archiv European Journal of Physiology. 1983;397(2):164-5.
37. 37. Rogers JC, Qu Y, Tanada TN, Scheuer T, Catterall WA. Molecular determinants of high affinity binding of α-scorpion toxin and sea anemone toxin in the S3-S4 extracellular loop in domain IV of the Na+ channel α subunit. Journal of Biological Chemistry. 1996;271(27):15950-62.
38. 38. Mouhat S, Jouirou B, Mosbah A, De Waard M, Sabatier J-M. Diversity of folds in animal toxins acting on ion channels. Biochemical Journal. 2004;378(3):717-26.
39. 39. Possani LD, Becerril B, Delepierre M, Tytgat J. Scorpion toxins specific for Na+‐channels. The FEBS journal. 1999;264(2):287-300.
40. 40. Possani LD, Becerril B, Tytgat J, Delepierre M. High affinity scorpion toxins for studying potassium and sodium channels. Ion Channel Localization: Methods and Protocols. 2001:145-65.
41. 41. Ma R, Cui Y, Zhou Y, Bao Y-M, Yang W-Y, Liu Y-F, et al. Location of the analgesic domain in Scorpion toxin BmK AGAP by mutagenesis of disulfide bridges. Biochemical and biophysical research communications. 2010;394(2):330-4.
42. 42. Goudet C, Chi C-W, Tytgat J. An overview of toxins and genes from the venom of the Asian scorpion Buthus martensi Karsch. Toxicon. 2002;40(9):1239-58.
43. 43. Karbat I, Frolow F, Froy O, Gilles N, Cohen L, Turkov M, et al. Molecular basis of the high insecticidal potency of scorpion α-toxins. Journal of Biological Chemistry. 2004;279(30):31679-86.
44. 44. Dehghan Z, Ayat H, Ahady A. Bioinformatics analysis of analgesic-antitumor like peptide from Iranian scorpion Mesobuthus eupeus. Journal of Shahrekord Uuniversity of Medical Sciences. 2016;18.
45. 45. Terlau H, Olivera BM. Conus venoms: a rich source of novel ion channel-targeted peptides. Physiological reviews. 2004;84(1):41-68.
46. 46. Nicke A, Wonnacott S, Lewis RJ. α‐Conotoxins as tools for the elucidation of structure and function of neuronal nicotinic acetylcholine receptor subtypes. The FEBS journal. 2004;271(12):2305-19.
47. 47. Ekberg J, Jayamanne A, Vaughan CW, Aslan S, Thomas L, Mould J, et al. μO-conotoxin MrVIB selectively blocks Nav1. 8 sensory neuron specific sodium channels and chronic pain behavior without motor deficits. Proceedings of the National Academy of Sciences. 2006;103(45):17030-5.
48. 48. Malmberg AB, Gilbert H, McCabe RT, Basbaum AI. Powerful antinociceptive effects of the cone snail venom-derived subtype-selective NMDA receptor antagonists conantokins G and T. Pain. 2003;101(1):109-16.
49. 49. Sharpe IA, Gehrmann J, Loughnan ML, Thomas L, Adams DA, Atkins A, et al. Two new classes of conopeptides inhibit the α1-adrenoceptor and noradrenaline transporter. Nature neuroscience. 2001;4(9):902-7.
50. 50. Dutton JL, Craik DJ. alpha Conotoxins Nicotinic Acetylcholine Receptor Antagonists as Pharmacological Tools and Potential Drug Leads. Current medicinal chemistry. 2001;8(4):327-44.
51. 51. Knapp O, McArthur JR, Adams DJ. Conotoxins targeting neuronal voltage-gated sodium channel subtypes: potential analgesics? Toxins. 2012;4(11):1236-60.
52. 52. Adams DJ, Berecki G. Mechanisms of conotoxin inhibition of N-type (Cav2. 2) calcium channels. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2013;1828(7):1619-28.
53. 53. Motin L, Yasuda T, Schroeder CI, Lewis RJ, Adams DJ. ω‐Conotoxin CVIB differentially inhibits native and recombinant N‐and P/Q‐type calcium channels. European Journal of Neuroscience. 2007;25(2):435-44.
54. 54. Bowersox SS, Luther R. Pharmacotherapeutic potential of omega-conotoxin MVIIA (SNX-111), an N-type neuronal calcium channel blocker found in the venom of Conus magus. Toxicon. 1998;36(11):1651-8.
55. 55. Skov MJ, Beck JC, de Kater AW, Shopp GM. Nonclinical safety of ziconotide: an intrathecal analgesic of a new pharmaceutical class. International journal of toxicology. 2007;26(5):411-21.
56. 56. Miljanich G. Ziconotide: neuronal calcium channel blocker for treating severe chronic pain. Current medicinal chemistry. 2004;11(23):3029-40.
57. 57. McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatric disease and treatment. 2007;3(1):69.
58. 58. http://www.cancernetwork.com.
59. 59. Xiao Y, Liang S. Inhibition of neuronal tetrodotoxin-sensitive Na+ channels by two spider toxins: hainantoxin-III and hainantoxin-IV. European journal of pharmacology. 2003;477(1):1-7.
60. 60. Wang M, Rong M, Xiao Y, Liang S. The effects of huwentoxin-I on the voltage-gated sodium channels of rat hippocampal and cockroach dorsal unpaired median neurons. Peptides. 2012;34(1):19-25.
61. 61. Chen J-Q, Zhang Y-Q, Dai J, Luo Z-M, Liang S-P. Antinociceptive effects of intrathecally administered huwentoxin-I, a selective N-type calcium channel blocker, in the formalin test in conscious rats. Toxicon. 2005;45(1):15-20.
62. 62. Ying R, Lin L, Peng H, Qin CJ. The antinociceptive efficacy of HWTX-I epidurally administered in rheumatoid arthritis rats. International journal of sports medicine. 2011;32(11):869-74.
63. 63. Liu Z, Dai J, Dai L, Deng M, Hu Z, Hu W, et al. Function and solution structure of Huwentoxin-X, a specific blocker of N-type calcium channels, from the Chinese bird spider Ornithoctonus huwena. Journal of Biological Chemistry. 2006;281(13):8628-35.
64. 64. Peng K, Shu Q, Liu Z, Liang S. Function and solution structure of huwentoxin-IV, a potent neuronal tetrodotoxin (TTX)-sensitive sodium channel antagonist from Chinese bird spider Selenocosmia huwena. Journal of Biological Chemistry. 2002;277(49):47564-71.
65. 65. Xiao Y, Bingham J-P, Zhu W, Moczydlowski E, Liang S, Cummins TR. Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration. Journal of Biological Chemistry. 2008.
66. 66. Middleton RE, Warren VA, Kraus RL, Hwang JC, Liu CJ, Dai G, et al. Two tarantula peptides inhibit activation of multiple sodium channels. Biochemistry. 2002;41(50):14734-47.
67. 67. Schmalhofer WA, Calhoun J, Burrows R, Bailey T, Kohler MG, Weinglass AB, et al. ProTx-II, a selective inhibitor of NaV1. 7 sodium channels, blocks action potential propagation in nociceptors. Molecular pharmacology. 2008;74(5):1476-84.
68. 68. Pu X, Wong P, Gopalakrishnakone P. A novel analgesic toxin (hannalgesin) from the venom of king cobra (Ophiophagus hannah). Toxicon. 1995;33(11):1425-31.
69. 69. Gopalakrishnakone P. Hannalgesin from king cobra venom releases nitric oxide (NO) and activates nitric oxide synthase (NOS). Toxicon. 1996;6(34):622.
70. 70. Salinas M, Besson T, Delettre Q, Diochot S, Boulakirba S, Douguet D, et al. Binding site and inhibitory mechanism of the mambalgin-2 pain-relieving peptide on acid-sensing ion channel 1a. Journal of Biological Chemistry. 2014;289(19):13363-73.
71. 71. Diochot S, Baron A, Salinas M, Douguet D, Scarzello S, Dabert-Gay A-S, et al. Black mamba venom peptides target acid-sensing ion channels to abolish pain. Nature. 2012;490(7421):552-5.