KRONİK AĞRI MEKANİZMALARI, NÖRALTERAPİ ve ORTOMOLEKÜLER DESTEK TEDAVİLERİ

Öz

Bu derlemede kronik ağrı mekanizmaları; kronik ağrıya Nöralterapi yaklaşımı, ortomoleküler ürünler ve etki mekanizmaları incelenmiştir. Kronik ağrı; Nöralterapide kullanılan lokal anesteziklerin; ağrı yolakları, nörojenik inflamasyon, bozucu alanlar ve santral ağrı hafızasını oluşturan yapıların üzerindeki etkileri ile düzenlenebilmektedir. Ortomoleküler tıp; “vitaminler, mineraller, amino asitler, eser elementler ve yağ asidi gibi” doğal molekülleri, bedenin ihtiyacına göre ve doğru miktarlarda kullanarak bireysel biyokimyasal temelli dengesizlikleri veya eksiklikleri düzeltme girişimlerini içermektedir. Kronik ağrı patofizyolojisinde önemli bir yer tutan glutamat ve NMDA reseptörleri üzerinde etkileri bulunan ortomoleküler ürünler destek tedavilerinde kullanılmaktadır. Kronik ağrıya yaklaşım bütünsel bir bakış açısı gerektirmektedir. Kronik inflamasyon, asidik yıkım ürünlerinin artışı, bağışıklık ve hormonal sistemin kronik ağrıdaki yeri göz ardı edilemez. Bu makalenin konusu içinde yer almamasına rağmen, sağlıklı bir bağırsak florası oluşturulması, enterik sistem regülasyonunun sağlanması, bağ dokusunun temizlenmesi ve şelasyon kronik ağrıya bütünsel yaklaşımın kilit taşlarıdır (1). Nöralterapi uygulamaları ve bütünsel bakış açısına uygun ortomoleküler desteklerle hastaların kronik ağrı sağaltımına katkı sağlanabilecektir

Anahtar Kelimeler

• Kronik Ağrı, Lokal Anestezikler, Nöralterapi, NMDA, Glutamat, Ortomoleküler.

A REVIEW: MECHANISMS OF CHRONIC PAIN, NEURALTHERAPY and ORTHOMOLECULAR SUPPORTIVE TREATMENT

Öz

In this review; mechanisms of chronic pain; Neuraltherapy approach to chronic pain, orthomolecular products for chronic pain and mechanisms of actions of both Neuraltherapy and orthomolecular products have been examined. Chronic pain relief can be provided by the local anesthetics that is used in Neuraltherapy practice; with the effects on Pain pathways, neurogenic inflammation, disturbing fields, and effects on structures that constitute the central pain memory. Orthomolecular medicine includes attempts to correct individual biochemical-based imbalances or deficiencies by using natural molecules such as “vitamins, minerals, amino acids, trace elements and fatty acids” according to the body’s needs and in the right quantities.The orthomolecular products that have effects on glutamate and NMDA receptors -which plays an important role in pathophysiology of chronic pain- are used in supportive therapies for chronic pain.The approach to chronic pain requires a holistic perspective. Chronic inflammation, increased acidic degradation products, and the immune-hormonal system dysfunctions; their role in the formation of chronic pain cannot be ruled out. Despite the absence of the subject of this article; the establishment of a healthy intestinal flora, the regulation of the enteric system, the cleansing of connective tissue-basic matrix- and chelation are the keystones of a holistic approach to chronic pain (1). Methods of Neuraltherapy and orthomolecular support for a holistic perspective will contribute to the chronic pain relief of patients

Anahtar Kelimeler

• Chronic Pain, Local Anethetics, Neuraltherapy, NMDA, Glutamate, Orthomolecular.

Kaynakça

1. Nazlıkul H. Dirençli Vakalara Yaklaşım Bölüm XX. 343-347. Nöralterapi. 2010.
2. Turk, D.C.; Okifuji, A. (2001). Pain Terms and taxonomies. In Loeser, D.; Butler, S. H.; Chapman, J.J.; Turk, D. Bonica’s Management of Pain (3rd ed.). Lippincott Williams & Wilkins. pp. 18–25
3. Prof Dr Avni Babacan. Ağrı, ağrı yolları ve Ağrılı hastaya yaklaşım. med. gazi.edu.tr
4. Nazlıkul H. Sinir Sistemi Fizyolojisi Bölüm 5.82-84. Nöralterapi. 2010
5. Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N-methyl- D-aspartate (NMDA) receptors in pain: a review. Anesth Analg. Oct;97(4):1108-16. 2003.
6. Mehta A, Prabhakar M, Kumar P, Deshmukh R, Sharma PL. Excitotoxicity: bridge to various triggers in neurodegenerative disorders. Eur. J. Phar- macol. 698(1–3), 6–18 (2013).
7. Chizh BA. Novel approaches to targeting glutamate receptors for the treatment of chronic pain: review article. Amino Acids 23(1–3), 169– 176.2002)
8. Rodriguez PL, Jiang S, Fu Y, Avraham S, Avraham HK. The proinflamma- tory peptide substance P promotes blood–brain barrier breaching by breast cancer cells through changes in microvascular endothelial cell tight junctions. Int. J. Cancer 134(5), 1034–1044. 2014.

9. Dossantos MF, Holanda-Afonso RC, Lima RL, Dasilva AF, Moura-Neto V. The role of the blood-brain barrier in the development and treatment of migraine and other pain disorders. Front. Cell. Neurosci. 8, 302. 2014
10. Hawkins RA. The blood–brain barrier and glutamate. Am. J. Clin. Nutr. 90(3), S867–S874. 2009.
11. Fang J, An X, Chen S, Yu Z, Ma Q, Qu H. Case–control study of GRIA1 and GRIA3 gene variants in migraine. J. Headache Pain 17(1), 2. 2015.
12. Niddam DM, Tsai SY, Lu CL, Ko CW, Hsieh JC. Reduced hippocampal gluta- mate–glutamine levels in irritable bowel syndrome: preliminary findings using magnetic resonance spectroscopy. Am. J. Gastroenterol. 106(8), 1503–1511. 2011.
13. Kim YK, Na KS. Role of glutamate receptors and glial cells in the pathoph- ysiology of treatment-resistant depression. Prog. Neuropsychopharma- col. Biol. Psychiatry doi:10.1016/j.pnpbp.2016.03.009 2016.
14. Peres MF, Zukerman E, Senne Soares CA, Alonso EO, Santos BF, Faulha- ber MH. Cerebrospinal fluid glutamate levels in chronic migraine. Cepha- lalgia 24(9), 735–739. 2004.
15. Harris RE. Elevated excitatory neurotransmitter levels in the fibromyalgia brain. Arthritis Res. Ther. 12(5), 141. 2010.
16. Zeilhofer HU, Wildner H, Yevenes G. Fast synaptic inhibition in spinal sen- sory processing and pain control. Phisiol Rev. 103-235.2012.
17. Savic Vujovic KR, Vuckovic S, Srebro D et al. A synergistic interaction bet- ween magnesium sulphate and ketamine on the inhibition of acute noci- ception in rats. Eur. Rev. Med. Pharmacol. Sci. 19(13), 2503–2509 (2015).
18. Anderson CT, Radford RJ, Zastrow ML et al. Modulation of extrasynap- tic NMDA receptors by synaptic and tonic zinc. Proc. Natl Acad. Sci.USA 112(20), E2705–E2714 (2015).
19. Amadasi A, Bertoldi M, Contestabile R et al. Pyridoxal 5′-phosphate enz- ymes as targets for therapeutic agents. Curr. Med. Chem. 14(12),1291– 1324 (2007).
20. Keleshian VL, Kellom M, Kim HW et al. Neuropathological responses to chro- nic NMDA in rats are worsened by dietary n-3 PUFAdeprivation but are not ameliorated by fish oil supplementation. PLoS ONE 9(5), e95318 (2014).
21. Wang JY, Wen LL, Huang YN, Chen YT, Ku MC. Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidativestress and indirect protection via suppression of glia-mediated inflammation. Curr. Pharm. Des. 12(27), 3521–3533 (2006).
22. Pfister M, Fischer L. Die Behandlung des komplexen regionalen Schmerzsy- ndroms der oberen Extremität mit wiederholter Lokalanästhesie des Ganglion stellatum. Praxis 2009;98:247-257.
23. Cassuto D, Sinclair R, Bonderovic M. Anti-inflammatory properties of lo- cal anesthetics and their present and potential clinical implications. Acta Anaesthesiol Scand 2006;50:265–282.
24. Straub RH, Wiest R, Strauch UG, Härle P, Schölmerich J. The role of the sympathetic nervous system in intestinal inflammation. Gut 2006;55:1640–1649. [doi: 10.1136/gut.2006.091322.
25. Day M. Sympathetic Blocks: The Evidence. Pain Practice, 8:2.2008, 98-109.
26. Spinal recordings suggest that wide-dynamic-range neurons mediate sympathetically maintained pain. Roberts WJ, Foglesong ME, Pain, Volu- me:34:3 September 1988, Pages 289–304
27. Kirlowa I, Teliban A, Gorodestkaya N. Effect of local and intraveno- us lidocaine on ongoing activity in injured afferent nerve fibers. Pain, 2011;152:1562-1571.
28. Watkins LR, Hutchinson MR, Milligan ED, Maier SF. “Listening” and “tal- king” to neurons: Implications of immune activation for pain control and increasing the efficacy of opioids. Brain Res Rev 2007;56:148-169.
29. Delhumeau A et al. Indications for the use of magnesium in anesthesia and intensive care. Ann Fran D’anest-Rean.1995;14:406-16.
30. Mayer ML et al. Voltage dependent block by Mg of NMDA response in spinal cord neurons. Nature 1984: 309:261-263.
31. Mc Carthy RJ et al. Antinociceptive potentiation and attenuation of tole- rance by intrathecal co-infusion of magnesium sulphate and morphine in rats. Anesth Analg 1998; 86:830-836.
32. Mauskop A, Altura Bt, Cracco RQ, Altura BM. Intravenous magnesium sulfate relieves cluster headaches in patients with low serum ionized magnesium levels. Headache. 1995;35(10):597-600.
33. Mauskop A, Altura Bt, Altura BM. Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios in women with mens- trual migraine. Headache. 2002;42(4):242-248.
34. Peikert A, Wilimzig C, Köhne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia. 1996;16(4):257-263.
35. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine–a double-blind placebo-controlled study. Cephalalgia. 1996; 16(6):436-440.
36. Bigal Me, Bordini CA, tepper SJ, Speciali JG. Intravenous magnesium sulphate in the acute treatment of migraine without aura and migraine with aura. A randomized, double-blind, placebo-controlled study. Cep- halalgia. 2002;22(5):345-353
37. Begon S et al. Magnesium Increases Morphine Analgesic Effect in Diffe- rent Experimental Models of Pain. Anesthesiol Mar;96(3):627-32 2002
38. Oliveria GS et al. Perioperative systemic magnesium to minimize posto- perative pain. A Meta-Analysis of Randomized Controlled Trials. Anest- hesiology; 119:178-190. 2013
39. Levaux Ch. et al. Effect of intra-operative magnesium sulphate on pain relief and patient comfort after major lumbar orthopaedic surgery. Ana- esthesia, 58;131–135. 2003.
40. Ramsden CE et al, Dietary linoleic acid-induced alterations in pro- and anti-nociceptive lipid autacoids: Implications for idiopathic pain syndro- mes? Molecular Pain.Volume 12: 1–14. 2016.
41. Hill CL, et al. Fish oil in knee osteoarthritis: a randomised clinical trial of low dose versus high dose Ann Rheum Dis 2016;75:23–29. doi:10.1136/ annrheumdis-2014-207169.
42. Proudman SM et al, Fish oil in recent onset rheumatoid arthritis: a randomised, double-blind controlled trial within algorithm-based drug use. Ann Rheum Dis 2015;74:89–95. doi:10.1136/annrheum- dis-2013-204145.
43. Proudman SM et al. Dietary Omega-3 fats for treatment of inflammatory joint disease:efficacy and utility. Rheum Dis Clin North Am 2008;34:469-79.
44. Serhan CN et al. Resolving inlammation:dual anti-inflammatory and pro- resolution lipid mediators. Nat Rev Immunol 2008;8:349-61.
45. James MJ et al. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 200;71 (suppl):343S-8S
46. Goldberg RJ, Katz JA. A meta analysis of the analgesic effects of omega-3 polyunsaturated fatty acid supplementation for he inflammatory joint pain. Pain 2007;129:210-23.
47. Fortin PR et al. Validation of a meta analysis: the effect of fish oil in rhe- umatoid arthritis. J Clin Epidemiol 1995;48:1379-90.
48. Kirksey A, Morré DM, Wasynczuk AZ. Neuronal development in vitamin B6 deficiency. Ann N Y Acad Sci. 1990;585:202-18.
49. Aufiero E, Stitik TP, Foye PM, Chen B. Pyridoxine hydrochloride treatment of carpal tunnel syndrome: a review. Nutr Rev.2004 Mar;62(3):96-104.
50. Harshmann RM, Aldoori W Canadian Family Physician Vol 53: july . 1161- 1162. 2007)
51. Ellis JM et al. Response of vitamin B-6 deficiency and the carpal tunnel syndrome to pyridoxine. Proc. NatL Acad. Sci. USA. Vol. 79, pp. 7494- 7498, December 1982.
52. Stracke H, et al, Benfotiamine in diabetic polyneuropathy (BENDIP): re- sults of a randomised, double blind, placebo-controlled clinical study. Exp Clin Endocrinol Diabetes 2008; 116(10): 600-605).
53. Housseinzadeh H, Anti-Nociceptive and Anti-Inflammatory effects of Cyanocobalamin (Vit B12) against acute and chronic pain and Inflam- mation in mice. (Arzneimittelforschung 2012; 62(07): 324-329 DOI: 10.1055/s-0032-1311635.
54. Mauro GL et al. Vitamin B12 in low back pain: A randomised, double- blind, placebo-controlled study. Eur Rev Med Pharmacol Sci. May- Jun;4(3):53-8. 2000.
55. C.-Z. Yu et al. Systematic administration of B vitamins attenuates neuro- pathic hyperalgesia and reduces spinal neuron injury following tempo- rary spinal cord ischaemia in rats. Eur J Pain2014 Jan;18(1):76-85. doi: 10.1002/j.1532-2149.2013.00390.
56. Alshuaib WB, Mathew MV. Vitamins C and E modulate neuronal potassi- um currents. J Membr Biol. 2006 Apr;210(3):193-8. Epub 2006 Aug 14.
57. Visser EJ. Is migraine a complex regional pain syndrome of the brain? Migraine prophylaxis with vitamin C? Pain Pract.; 11(2):199-200. 2011.
58. Borkum JM. Migraine triggers and oxidative stress: a narrative review and synthesis. Headache 56(1), 12–35 (2016).
59. Wang JY, Wen LL, Huang YN, Chen YT, Ku MC. Dual effects of antioxidants in neurodegeneration: direct neuroprotection against oxidative stress and indirect protection via suppression of glia-mediated inflammation. Curr. Pharm. Des. 12(27), 3521–3533 (2006).
60. Chen JY et al. Plasma vitamin C is lower in postherpetic neuralgia pati- ents and administration of vitamin C reduces spontaneous pain but not brush-evoked pain. Clin J Pain. 25(7):562-9. 2009.
61. Sunitha Malay, Kevin C. Chung. Testing the Validity of Preventing Comp- lex Regional Pain Syndrome With Vitamin C After Distal Radius Fracture. J Hand Surg Am. 2014 Nov;39(11):2251-7. doi: 10.1016/j.jhsa.2014.08.009
62. Chen S et al. Effect of Perioperative Vitamin C Supplementation on Pos- toperative Pain and the Incidence of Chronic Regional Pain Syndrome: A Systematic Review and Meta-Analysis. Clin J Pain. 2016; 32(2):179-85.
63. Nozaki C et al. Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit. Nat Neurosci. 2011; 14(8):1017-22.
64. Stefano L et al. Zinc in the physiology and pathology of the CNS. Nature Reviews Neuroscience 10, 780-791 (November 2009).
65. Frederickson CJI et al.Importance of zinc in the central nervous system: the zinc-containing neuron. J Nutr. 2000 May;130(5S Suppl):1471S-83S
66. Jo SM et al. Depletion of vesicular zinc in dorsal horn of spinal cord cau- ses increased neuropathic pain in mice. Biometals. 2008 Apr;21(2):151- 8. Epub 2007 Jun 15.
67. Turner MK, et al. Prevalence and Clinical Correlates of Vitamin D Inade- quency among patients with Chronic Pain. Pain Medicine. Volume 9, (8), 979-984.2008.
68. Lasco A, MD; Catalano A, MD; Benvenga, S MD. Improvement of Primary Dysmenorrhea Caused by a Single Oral Dose of Vitamin D: Results of a Randomized, Double-blind, Placebo-Controlled Study. Arch Intern Med. 2012;172(4):366-367.
69. Plotnikoff GA, Quigley JM, Prevalence of Severe Hypovitaminosis D in Pa- tientsWith Persistent, Nonspecific Musculoskeletal Pain. Mayo Clin Proc. 2003;78:1463-1470
70. Yılmaz H, Bodur S, Karaca G. Premenopozal Erişkin Kadınlarda Vitamin D Düzeyi ile Kronik Ağrı ve Depresyon Arasındaki ilişki. Türk Fiz Tıp Rehab Derg 2014;60:121-5.
71. Faraj SA, Mutairi KA, Vitamin D Deficiency and Chronic Low Back Pain in Saudi Arabia. SPINE Volume 28, Number 2, 177–179. 2003.