Nitrik Oksit Sentaz NOS İnhibitörlerinin Sıçanlarda Çok Düşük Frekanslı Manyetik Alanın İndüklediği Analjezi Üzerine Etkileri
Year 2017,
Volume: 27 Issue: 4, 121 - 128, 01.12.2017
Ercan Özdemir
Ayşe Demirkazık
Ahmet Şevki Taşkıran
Olca Kılınç
Gökhan Arslan
Abstract
Amaç: Elektromanyetik alanın EMA farklı ağrı türlerini azalttığı bilinmektedir. Bununla birlikte, manyetik alanın analjezik etki mekanizması tam olarak anlaşılamamıştır. Bu çalışmanın amacı, nitrik oksit sentaz NOS inhibitörlerinin sıçanlarda çok düşük frekanslı EMA maruziyeti ile oluşan analjezi üzerine etkilerini araştırmaktır.Gereç ve Yöntem: Bu çalışmada 72 yetişkin erkek Wistar albino sıçan yaklaşık 230 ± 12 g ağırlığında kullanıldı. Sıçanlar, 22 ± 2 °C oda sıcaklığında, 12 saat aydınlık/karanlık siklusun sağlandığı ve ses yalıtımı olan ortamda tutuldu. Elektromanyetik alan 50 Hz , her gün dört defa 30 dakika süre ve 15 dakika aralıklar ile 15 gün boyunca uygulandı. Analjezik etki ölçümü tail-flick ve hot-plate testleri ile gerçekleştirildi. Analjezi testinden önce sıçanlara nitrik oksit donörü SNAP 30 mg/kg ve NOS inhibitörleri L-NAME 40 mg/kg ve 7-NI 25 mg/kg intraperitoneal olarak enjekte edildi. Verilerin istatistiksel analizinde varyans analizi iki yönlü ANOVA kullanılmış ve çoklu karşılaştırma Tukey testleri ile yapıldı. İstatistiksel olarak anlamlılık düzeyi p
References
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- Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Derma- tol 2007;127:514-25.
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- Medina FJ, Tşnez I. Huntington’s disease: the value of transcranial meganetic stimulation. Curr Med Chem 2010;17:2482-91.
- Cuccurazzu B, Leone L, Podda MV, et al. Exposure to extre- mely low-frequency (50 Hz) electromagnetic Şelds enhan- ces adult hippocampal neurogenesis in C57BL/6 mice. Exp Neurol 2010; 226:173-82.
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- Baltaci AK, Mogulkoc R, Salbacak A, Celik I, Sivrikaya A. The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues. Bratisl Lek Listy 2012;113:400-3.
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- Kavaliers M, Ossenkopp KP, Tysdale DM. Evidence for the involvement of protein kinase C in the modulation of morphine- induced ‘analgesia’ and the inhibitory effects of exposure to 60-Hz magnetic Şeld in the snail, Cepaea ne- moralis. Brain Research 1991;554:65-71.
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- Johnson MT, Waite LR, Nindl G. Noninvasive treatment of inflammation using electromagnetic Şelds: Current and emerging therapeutic potential. Biomed Sci Instrum 2004; 40: 469–74.
- Lai H, Carino M. Intracerebroventricular injection of mu- and delta-opiate receptor antagonists block 60 Hz magnetic Şeld-induced decreases in cholinergic activity in the fron- tal cortex and hippocampus of the rat. Bioelectromagnetics 1998;19:432–7.
- Bao X, Shi Y, Huo X, and Song T. A possible involvement of ß-endorphin, Substance P, and serotonin in rat analge- sia induced by extremely low frequency magnetic field. Bioelectromagnetics 2006; 27: 467-72.
- Kavaliers M, Ossenkopp K-P. Magnetic fields inhibit opio- id - mediated “analgesic” behaviour of the terrestrial snails, Cepaea nemoralis. Journal of Comparative Physiology A 1988;162:551-8.
- Sieron A, Labus L, Nowak P, et al. Alternating extremely low frequency magnetic field increases turnover of dopami- ne and serotonin in rat frontal cortex. Bioelectromagnetics 2004; 25: 426-30.
- Pilla AA. Electromagnetic Şelds instantaneously modulate nitric oxide signaling in challenged biological systems. Bio- chemical and Biophysical Research Communications 2012; 426: 330-3.
- Cheng G, Zhai Y, Chen K, et al. Sinusoidal electromagnetic Şeld stimulates rat osteoblast differentiation and maturati- on via activation of NO-cGMP-PKG pathway. Nitric Oxide 2011; 25: 316–25.
- Patruno A, Amerio P, Pesce M, et al. Extremely low frequ- ency electromagnetic Şelds modulate expression of indu- cible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing. Bri- tish Journal of Dermatology 2010; 162: 258–66.
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- Wong CS, Cherng CH, Tung CS. Intrathecal administrati- on of excitatory amino acid receptor antagonists or nitric oxide synthase inhibitor reduced autotomy behavior in rats. Anesth Analg 1998;87:605-8.
- Kanaan SA, Saade NE, Haddad JJ, et al. Endotoxin-induced local inflammation and hyperalgesia in rats, a new model for inflammatory pain. Pharmacology 1996;66:373–9.
- Ramabadran K, Bansinath M, Turndorf H, Puig MM. The hyperalgesic effect of naloxone is attenuated in streptozo- tocin-diabetic mice. Psychopharmacology (Berl.) 1989; 97:169–74.
- Martin LJ, Persinger MA. Thermal analgesia induced by 30- min exposure to 1 mT burst-Şring magnetic Şelds is strong- ly enhanced in a dose-dependent manner by the α2 agonist clonidine in rats. Neurosci Lett 2004;366:226–9.
- Shupak NM, Hensel JM, Cross-Mellor SK, Kavaliers M, Prato FS, Thomas AW. Analgesic and behavioral effects of a 100 mT speciŞc pulsed extremely low frequency magnetic Şeld on control and morphine treated CF-1mice. Neurosci Lett 2004; 354:30-3.
- Nindl G, Balcavage WX, Vesper DN, et al. Experiments showing that electromagnetic fields can be used to treat inflammatory diseases. Biomed Sci Instrum 2000; 36: 7-13.
- Kavaliers M, Ossenkopp KP. Tolerance to morphine-in- duced analgesia inmice: Magnetic Şelds function as envi- ronmental speciŞc cues and reduce tolerance development. Life Sci 1985;37:1125-35.
- Kavaliers M, Ossenkopp KP. Repeated naloxone treatments and exposures toweak 60 Hzmagnetic Şelds have ‘analge- sic’effects in snail. Brain Res 1993;620:159-62.
- Thomas AW, Kavaliers M, Prato FS, Ossenkopp KP. Pulsed magnetic Şeld induced ‘‘analgesia’’ in the Land Snail, Cepa- ea nemoralis, and the effects of m,d, and k opioid receptor agonists/antagonists. Peptides 1997a;18:703-9.
- Thomas AW, Kavaliers M, Prato FS, Ossenkopp KP. Anal- gesic effects of a speciŞc pulsed magnetic Şeld in the land snail, Cepaea nemoralis: Consequences of repeated exposu- res, relations to tolerance and cross-tolerance with DPDPE. Peptides 1997b;19:333-42.
- Rosen A, Zhang YX, Lund I, Lundeberg T, Yu LC. Substan- ce P microinjected into the periaqueductal gray matter in- duces antinociception and is released following morphine administration. Brain Res 2004;1001:87-94.
- Atalık KE, Doğan N. Nitrik oksit ve fizyolojik etkileri. Genel Tıp Derg 1997;7:167-9.
- Makuch W, Mika J, Rojewska E, Zychowska M, Przewlocka B. Effects of selective and non-selective inhibitors of nitric oxide synthase on morphine- and endomorphin-1-induced analgesia in acute and neuropathic pain in rats. Neurophar- macology 2013;75: 445-57.
- Ozdemir E, Bagcivan I, Durmus N, Altun A, and Gursoy S. The nitric oxide–cGMP signaling pathway plays a sig- nificant role in tolerance to the analgesic effect of morp- hine. Canadian Journal of Physiology and Pharmacology 2011;89:89–95.
- Moore PK, Wallace P, Gaffen Z, Hart SL, Babbedge RC. Characterizationof the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovascular effects. Br J Pharmacol 1993;110:219-24.
- Handy RL, Wallace P, Gaffen ZA, Whitehead KJ, Moore PK. The antinociceptive effect of 1-(2-trifluoromethylp- henyl) imidazole (TRIM), a potentinhibitor of neuronal nitric oxide synthase in vitro, in the mouse. Br J Pharmacol 1995;116:2349-50.
- Bawin SM, Satmary WM, Jones RA, Adey WR, Zimmer- man G. Extremely low frequency magnetic Şeld disrupt rhythmic slow activity in rat hippocampal slices. Bioelect- romagnetics 1996; 17: 388–95.
- Yoshikawa T, Tanigawa M, Tanigawa T, Imai A, Hongo H, Kondo M. Enhancement of nitric oxide generation by low frequency electromagnetic Şeld. Pathophysiology 2000;7:131–5.
- Jeong JH, Kum C, Choi HJ, Park ES, Sohn UD. Extre- mely low frequency magnetic Şeld induces hyperalgesia in mice modulated by nitric oxide synthesis. Life Science 2006;78:1407–12.
- Machelska H, Labuz D, Przewlocki R, Przewlocki B. In- hibition of nitric oxide synthase enhance antinociception mediatedby mu, delta and kappa opioid receptors in acute and prolonged pain in the rat spinal cord. The Journal of Pharmacology and Experimental Therapeutics 1997; 282: 977–84.
Year 2017,
Volume: 27 Issue: 4, 121 - 128, 01.12.2017
Ercan Özdemir
Ayşe Demirkazık
Ahmet Şevki Taşkıran
Olca Kılınç
Gökhan Arslan
Abstract
Objective: It is known that the electromagnetic field EMF reduces the different types of pain. However, the mechanism of magnetic field analgesia is not fully understood. Our aim of this study is to investigate the effects of nitric oxide synthase NOS inhibitors on analgesia induced by extremely low frequency EMF in rats.Material and Methods: In this study were used 72 adult male Wistar albino rats approximately 230 ± 12 g . The rats were provided environment where is at 22 ± 2 °C room temperature, 12-hour light/dark cycle and insulated from sound. The application of electromagnetic field 50 Hz , the same times for 30 minutes each day for 15 days, and a total of four times every 15 minute intervals. The analgesic effect measurement was performed by tail-flick and hot-plate tests. Prior to analgesia test, nitric oxide donor SNAP 30 mg/kg and NOS inhibitors L-NAME 40 mg/kg and 7-NI 25 mg/kg were injected intraperitoneally in rats. In the statistical analyzes of the data, analysis of variance two-way ANOVA was used and the multiple comparison determined by Tukey tests. The level of statistically significant was expressed p
References
- Del Seppia C, Ghione S, Luschi P, Ossenkopp K-P, Choleris E, Kavaliers M. Pain perception and electromagnetic Şelds. Neuroscience and Biobehavioral Reviews 2007; 31:619-42.
- Sienkiewicz Z, Jones N, Bottomley A. Neurobehavio- ral effects of electromagnetic Şelds. Bioelectromagnetics 2005;7:116-26.
- Vallbona C, Richards T. Evolution of magnetic therapy from alternative to traditional medicine. Physical Medicine and Rehabilitation Clinics of North America 1999;10:729-54.
- Bachl N, Ruoff G, Wessner B, Tschan H. Electromagnetic interventions in musculoskeletal disorders. Clin Sports Med 2008; 27:87-105.
- Eming SA, Krieg T, Davidson JM. Inflammation in wound repair: molecular and cellular mechanisms. J Invest Derma- tol 2007;127:514-25.
- Arendash GW. Review of the evidence that transcranial electromagnetic treatment will be a safe and effective the- rapeutic against Alzheimer’s disease. Journal of Alzheimer’s Disease 2016;53:753-71.
- Medina FJ, Tşnez I. Huntington’s disease: the value of transcranial meganetic stimulation. Curr Med Chem 2010;17:2482-91.
- Cuccurazzu B, Leone L, Podda MV, et al. Exposure to extre- mely low-frequency (50 Hz) electromagnetic Şelds enhan- ces adult hippocampal neurogenesis in C57BL/6 mice. Exp Neurol 2010; 226:173-82.
- Keck ME, Sillaber I, Ebner K, et al. Acute transcranial mag- netic stimulation of frontal brain regions selectively modu- lates the release of vasopressin, biogenic amines and amino acids in the rat brain. Eur J Neurosci 2000;12:3713-20.
- Baltaci AK, Mogulkoc R, Salbacak A, Celik I, Sivrikaya A. The role of zinc supplementation in the inhibition of tissue damage caused by exposure to electromagnetic field in rat lung and liver tissues. Bratisl Lek Listy 2012;113:400-3.
- Bediz CS, Baltaci AK, Mogulkoc R, Oztekin E. Zinc supp- lementation ameliorates electromagnetic field-induced lipid peroxidation in the rat brain. Tohoku J Exp Med 2006;208:133-40.
- Ossenkopp K-P, Kavaliers M, Prato FS, Teskey GC, Sestini E, Hirst M. Exposure to nuclear magnetic resonance ima- ging procedure attenuates morphine-induced analgesia in mice. Life Science 1985;37:1507-14.
- Kavaliers M, Ossenkopp KP, Tysdale DM. Evidence for the involvement of protein kinase C in the modulation of morphine- induced ‘analgesia’ and the inhibitory effects of exposure to 60-Hz magnetic Şeld in the snail, Cepaea ne- moralis. Brain Research 1991;554:65-71.
- Kosar MI, Demir T, Demirkazik A, Deveci K, Ozdemir E, Gulturk S. Antinociceptive effects in normal and diabe- tic rats exposed to 50 hz magnetic field. Neurophysiology 2012;44:56-62.
- Thomas AW, White KP, Drost DJ, Cook CM, Prato FS. A comparison of rheumatoid arthritis and Şbromyalgia pa- tients and healthy controls exposed to a pulsed (200 mic- roT) magnetic Şeld: Effects on normal standing balance. Neurosci Lett 2001; 309:17-20.
- Johnson MT, Waite LR, Nindl G. Noninvasive treatment of inflammation using electromagnetic Şelds: Current and emerging therapeutic potential. Biomed Sci Instrum 2004; 40: 469–74.
- Lai H, Carino M. Intracerebroventricular injection of mu- and delta-opiate receptor antagonists block 60 Hz magnetic Şeld-induced decreases in cholinergic activity in the fron- tal cortex and hippocampus of the rat. Bioelectromagnetics 1998;19:432–7.
- Bao X, Shi Y, Huo X, and Song T. A possible involvement of ß-endorphin, Substance P, and serotonin in rat analge- sia induced by extremely low frequency magnetic field. Bioelectromagnetics 2006; 27: 467-72.
- Kavaliers M, Ossenkopp K-P. Magnetic fields inhibit opio- id - mediated “analgesic” behaviour of the terrestrial snails, Cepaea nemoralis. Journal of Comparative Physiology A 1988;162:551-8.
- Sieron A, Labus L, Nowak P, et al. Alternating extremely low frequency magnetic field increases turnover of dopami- ne and serotonin in rat frontal cortex. Bioelectromagnetics 2004; 25: 426-30.
- Pilla AA. Electromagnetic Şelds instantaneously modulate nitric oxide signaling in challenged biological systems. Bio- chemical and Biophysical Research Communications 2012; 426: 330-3.
- Cheng G, Zhai Y, Chen K, et al. Sinusoidal electromagnetic Şeld stimulates rat osteoblast differentiation and maturati- on via activation of NO-cGMP-PKG pathway. Nitric Oxide 2011; 25: 316–25.
- Patruno A, Amerio P, Pesce M, et al. Extremely low frequ- ency electromagnetic Şelds modulate expression of indu- cible nitric oxide synthase, endothelial nitric oxide synthase and cyclooxygenase-2 in the human keratinocyte cell line HaCat: potential therapeutic effects in wound healing. Bri- tish Journal of Dermatology 2010; 162: 258–66.
- Moore PK, Oluyomi A, Babbedge RC, Wallace P, Hart SL. L-NG-nitro arginine methyl ester exhibits antinociceptive activity in the mouse. Br J Pharmacol 1991;102: 198-202.
- Machelska H, Przew1ocki R, Radomski MW, Przew1ocka B. Differential effects of intrathecally and intracerebrovent- ricularly administered nitric oxide donors on noxious me- chanical and thermal stimulation. Pol J Pharmacol 1998; 50:407-15.
- Wong CS, Cherng CH, Tung CS. Intrathecal administrati- on of excitatory amino acid receptor antagonists or nitric oxide synthase inhibitor reduced autotomy behavior in rats. Anesth Analg 1998;87:605-8.
- Kanaan SA, Saade NE, Haddad JJ, et al. Endotoxin-induced local inflammation and hyperalgesia in rats, a new model for inflammatory pain. Pharmacology 1996;66:373–9.
- Ramabadran K, Bansinath M, Turndorf H, Puig MM. The hyperalgesic effect of naloxone is attenuated in streptozo- tocin-diabetic mice. Psychopharmacology (Berl.) 1989; 97:169–74.
- Martin LJ, Persinger MA. Thermal analgesia induced by 30- min exposure to 1 mT burst-Şring magnetic Şelds is strong- ly enhanced in a dose-dependent manner by the α2 agonist clonidine in rats. Neurosci Lett 2004;366:226–9.
- Shupak NM, Hensel JM, Cross-Mellor SK, Kavaliers M, Prato FS, Thomas AW. Analgesic and behavioral effects of a 100 mT speciŞc pulsed extremely low frequency magnetic Şeld on control and morphine treated CF-1mice. Neurosci Lett 2004; 354:30-3.
- Nindl G, Balcavage WX, Vesper DN, et al. Experiments showing that electromagnetic fields can be used to treat inflammatory diseases. Biomed Sci Instrum 2000; 36: 7-13.
- Kavaliers M, Ossenkopp KP. Tolerance to morphine-in- duced analgesia inmice: Magnetic Şelds function as envi- ronmental speciŞc cues and reduce tolerance development. Life Sci 1985;37:1125-35.
- Kavaliers M, Ossenkopp KP. Repeated naloxone treatments and exposures toweak 60 Hzmagnetic Şelds have ‘analge- sic’effects in snail. Brain Res 1993;620:159-62.
- Thomas AW, Kavaliers M, Prato FS, Ossenkopp KP. Pulsed magnetic Şeld induced ‘‘analgesia’’ in the Land Snail, Cepa- ea nemoralis, and the effects of m,d, and k opioid receptor agonists/antagonists. Peptides 1997a;18:703-9.
- Thomas AW, Kavaliers M, Prato FS, Ossenkopp KP. Anal- gesic effects of a speciŞc pulsed magnetic Şeld in the land snail, Cepaea nemoralis: Consequences of repeated exposu- res, relations to tolerance and cross-tolerance with DPDPE. Peptides 1997b;19:333-42.
- Rosen A, Zhang YX, Lund I, Lundeberg T, Yu LC. Substan- ce P microinjected into the periaqueductal gray matter in- duces antinociception and is released following morphine administration. Brain Res 2004;1001:87-94.
- Atalık KE, Doğan N. Nitrik oksit ve fizyolojik etkileri. Genel Tıp Derg 1997;7:167-9.
- Makuch W, Mika J, Rojewska E, Zychowska M, Przewlocka B. Effects of selective and non-selective inhibitors of nitric oxide synthase on morphine- and endomorphin-1-induced analgesia in acute and neuropathic pain in rats. Neurophar- macology 2013;75: 445-57.
- Ozdemir E, Bagcivan I, Durmus N, Altun A, and Gursoy S. The nitric oxide–cGMP signaling pathway plays a sig- nificant role in tolerance to the analgesic effect of morp- hine. Canadian Journal of Physiology and Pharmacology 2011;89:89–95.
- Moore PK, Wallace P, Gaffen Z, Hart SL, Babbedge RC. Characterizationof the novel nitric oxide synthase inhibitor 7-nitro indazole and related indazoles: antinociceptive and cardiovascular effects. Br J Pharmacol 1993;110:219-24.
- Handy RL, Wallace P, Gaffen ZA, Whitehead KJ, Moore PK. The antinociceptive effect of 1-(2-trifluoromethylp- henyl) imidazole (TRIM), a potentinhibitor of neuronal nitric oxide synthase in vitro, in the mouse. Br J Pharmacol 1995;116:2349-50.
- Bawin SM, Satmary WM, Jones RA, Adey WR, Zimmer- man G. Extremely low frequency magnetic Şeld disrupt rhythmic slow activity in rat hippocampal slices. Bioelect- romagnetics 1996; 17: 388–95.
- Yoshikawa T, Tanigawa M, Tanigawa T, Imai A, Hongo H, Kondo M. Enhancement of nitric oxide generation by low frequency electromagnetic Şeld. Pathophysiology 2000;7:131–5.
- Jeong JH, Kum C, Choi HJ, Park ES, Sohn UD. Extre- mely low frequency magnetic Şeld induces hyperalgesia in mice modulated by nitric oxide synthesis. Life Science 2006;78:1407–12.
- Machelska H, Labuz D, Przewlocki R, Przewlocki B. In- hibition of nitric oxide synthase enhance antinociception mediatedby mu, delta and kappa opioid receptors in acute and prolonged pain in the rat spinal cord. The Journal of Pharmacology and Experimental Therapeutics 1997; 282: 977–84.