Deneysel Nöropatik Ağrı Hayvan Modelleri
Özet
Nöropatik ağrı (NA), periferik veya santral sinir sistemindeki bir primer lezyon ya da hastalık sonucunda gelişebilen, teşhisi ve tedavisi zor, yaşam kalitesini ciddi ölçüde düşüren karmaşık ve kronik bir ağrı çeşididir. NA patofizyolojisinin tam olarak aydınlatılamamış olması ve mevcut ilaçların doz kısıtlayıcı yan etkileri nedeniyle, etkinliği yüksek yeni tedavi stratejilerinin geliştirilmesi için deneysel hayvan modellerine büyük ihtiyaç duyulmaktadır. Bu kapsamda literatürde periferik ve santral sinir hasarı, ilaca bağlı, hastalık kaynaklı ve kalıtımsal nöropati modelleri sıklıkla tercih edilmektedir. Periferik hasar modellerinde erişimi kolay olan siyatik sinir üzerinden aksotomi, kronik konstrüksiyon hasarı, parsiyel siyatik sinir ligasyonu ve spinal sinir ligasyonu yöntemleri kullanılırken; santral hasar modellerinde eksitotoksik, kontüzyon, fotokimyasal spinal kord hasarları ile spinal kord yarı kesisi ve talamik sendrom öne çıkmaktadır. İlaca bağlı modellerde paklitaksel, sisplatin, vinkristin gibi antikanser ilaçlar ile antiretroviraller kullanılırken, hastalık kaynaklı modellerde streptozosin ile diyabet, kanser, HIV ve Parkinson modelleri klinik durumları taklit etmektedir. Bu modellerin değerlendirilmesinde ise kuyruk çekme, hot-plate, ayak çekme ve formalin gibi termal, mekanik ve kimyasal uyaran testleri kullanılmaktadır. Sonuç olarak, deneysel nöropatik ağrı modelleri, ağrının mekanizmalarının aydınlatılması ve daha etkin tedavi seçeneklerinin geliştirilmesi için klinik öncesi çalışmalarda kritik öneme sahiptir.
Neuropathic pain (NP) is a complex and chronic type of pain that can develop as a result of a primary lesion or disease in the peripheral or central nervous system, which is difficult to diagnose and treat, and severely reduces the quality of life. Due to the incomplete elucidation of NP pathophysiology and the dose-limiting side effects of current medications, there is a great need for experimental animal models to develop highly effective new treatment strategies. In this context, peripheral and central nerve injury, drug-induced, disease-related, and hereditary neuropathy models are frequently preferred in the literature. While axotomy, chronic constriction injury, partial sciatic nerve ligation, and spinal nerve ligation methods are used on the easily accessible sciatic nerve in peripheral injury models; excitotoxic, contusion, photochemical spinal cord injuries, spinal cord hemisection, and thalamic syndrome stand out in central injury models. In drug-induced models, anticancer drugs such as paclitaxel, cisplatin, and vincristine, as well as antiretrovirals are used, while in disease-related models, streptozotocin-induced diabetes, cancer, HIV, and Parkinson's models mimic clinical conditions. In the evaluation of these models, thermal, mechanical, and chemical stimulus tests such as tail flick, hot-plate, paw withdrawal, and formalin are utilized. Consequently, experimental neuropathic pain models are of critical importance in preclinical studies for elucidating the mechanisms of pain and developing more effective treatment options.
Referanslar
Kankowski, S., et al., Neuropathicpain: Spotlightinganatomy, experimentalmodels, mechanisms, andtherapeuticaspects. European Journal of Neuroscience, 2021. 54(2): p. 4475-4496.
Scholz, J., et al., The IASP classification of chronicpainfor ICD-11: chronicneuropathicpain. Pain, 2019. 160(1): p. 53-59.
Finnerup, N.B., et al., Neuropathicpain: frommechanismstotreatment. Physiologicalreviews, 2021. 101(1): p. 259-301
Merskey, H. and N. Bogduk, Descriptions of chronicpainsyndromesanddefinition of painterm. IASP Press (Seattle), 1994.
Raja S.N., et al., There vised International Association for the Study of Paindefinition of pain: concepts, challenges, andcompromises. Pain, 2020; 161(9): p. 1976-1982.
Treede, R.D., et al., Neuropathicpain: redefinitionand a gradingsystemforclinicalandresearchpurposes. Neuroloy, 2008. 70(18): p. 1630-1635.
Charak, S., et al., Assessment and Management of Pain in Palliative Care. Suggestions for Addressing Clinical and Non-Clinical Issues in Palliative Care, 2021.167.
Şentürk, İ.A. Ağrı Değerlendirilmesi: Tipleri Ve Mekanizmaları. Medical Research Reports, 2018,1(3), 78-81.
Bekircan-Kurt, C.E.,et al.,NeuropathicPainFrequency in NeurologyOutpatients: A MulticenterStudy. ArchNeuropsychiatry, 2021. 58(4): p. 257-260.
Rosenberger, D.C., et al., Challenges of neuropathic pain: focus on diabetic neuropathy. Journal of Neural Transmission, 2020. 127(4): p. 589-624.
Luana, C., et al., Neuropathic pain. Nat. Rev. Dis. Primers, 2017. 3: 17.
Kösehasanoğulları, M., ve N. Yılmaz, Fibromiyalji sendromu ve nöropatik ağrı. Ege Tıp Bilimleri Dergisi, 2018. 1(1): p. 26-31.
Cavalli, E., et al., The neuropathic pain: An overview of the current treatment and future therapeutic approaches. International Journal of Immunopathology and Pharmacology, 2019. 33: 2058738419838383.
Bouali-Benazzouz, R., M. Landry, A. Benazzouz, and P. Fossat, Neuropathic pain modeling: Focus on synaptic and ion channel mechanisms. Progress in Neurobiology, 2021. 201: 102030.
Yam, M. F., Loh, Y. C., Tan, C. S., Khadijah Adam, S., Abdul Manan, N., & Basir, R. General pathways of pain sensation and the major neurotransmitters involved in pain regulation. International journal of molecular sciences, 2018. 19(8), 2164.
Iyengar S, Ossipov M.H, Johnson K.W. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain 2017; 158(4): 543-559
Anthony P. Ford ve Bradley J. Undem. The therapeutic promise of ATP antagonism at P2X3 receptors in respiratory and urological disorders. Front. Cell. Neurosci. 2013; 7: 267.
Yücel, A., & A. Çimen, Nöropatik ağrı: Mekanizmalar, tanı ve tedavi. Ağrı, 2005. 17: 1.
Kami, K., F. Tajima, and E. Senba, Exercise-induced hypoalgesia: potential mechanisms in animal models of neuropathic pain. Anatomical science international, 2017. 92(1): p. 79-90.
Alvites, R., et al. Peripheral nerve injury and axonotmesis: State of the art and recent advances. Cogent Medicine, 2018. 5(1):p.1466404.
Wall, P.D., et al. Autotomyfollowingperipheralnervelesions: experi mental anaesthesia dolorosa. Pain, 1979. 7(2): p.103-11.
Amir, R., and M. Devor, Ongoingactivity in neuroma affer ents bear ingretrograde sprouts. Brain Res, 1993. 630(1-2): p. 283-8.
HoKim, S., and J. MoChung, An experimental model for peripheral neuropa thyproduced bys egmental spinal nerveligation in therat.Pain, 1992. 50(3): p. 355–363
Ye, G.-L., et al., Ligation of mouse L4 and L5 spinal nervespro-ducesrobustallodynia wit hout major motor function deficit. Behavioural Brain Research, 2015. 276: p. 99–110.
Gopalsamy, B., et al., Experi mental characterization of thech ronicconstrictionin jury-inducedneuro pathicpain model in mice. Neurochemical Research, 2019. 44: p. 2123–2138.
Bennett, G.J., and Y.K. Xie, A peripher al mono neuropathy in ratthat produces disorders of painsensationlikethos eseen in man.Pain, 1988. 33(1): p. 87-107.
Authier, N., et al., An animal model of nociceptiveperipheralneuropathyfollowing re-peatedcisplatininjections.ExperimentalNeurology, 2003. 182(1): p. 12–20.
Ta, L. E., et al., Micewithcis-platin andoxaliplatin-inducedpainfulneuropathydevelopdistinctearlyresponsestot herma lstimuli. MolecularPain, 2009. 5(1): p. 1-11.
Takasaki, I., et al., Allodynia and hyperal gesiain duced by Herpes simplex virustype- 1 infection in mice. Pain, 2000. 86: p. 95–101.
Ahlgren S. C., and J.D. Levine, Mechanicalhyperalgesia in streptozotocin diabeticrats. Neuroscience, 1993. 52(4): p. 1049–1055.
Murakami, T., et al., Development of sensoryneuropathy in strep tozotocin induced diabetic mice. Brain and Behavior, 2013. 3, p. 35–41
Wall, P.D., et al., Auto tomy following peripheral nervelesions: experimental an aesthesia dolorosa. Pain, 1979. 7(2): p.103-11.
Sacerdote, P., et al., Transient early expression of TNF-α sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy. Neurosci Lett, 2008. 436(2): p. 210-3.
Muthuraman, A., A.S. Jaggi, N. Singh, and D. Singh, Ameliorative effects of amiloride and pralidoxime in chronic constriction injury and vincristine- induced painful neuropathy in rats. Eur J Pharmacol, 2008. 587(1-3): p. 104-11.
Jaggi, A.S., V. Jain, and N. Singh, Animal models of neuropathic pain. FundamClinPharmacol, 2011. 25(1): p. 1-28.
Seltzer, Z., R. Dubner, and Y. Shir, A novelbehavioral model of neuro pathic pain disorders produced in ratsbypartialsciaticnerveinjury. Pain, 1990. 43: p. 205-218.
Wang, L.X. and Z.J. Wang, Animaland cellular models of chronicpain. Adv Drug Deliv Rev, 2003. 55: p. 949-65.
Kim, S.H., J.M. Chung, An Experimental Model For Peripheral Neuropathy Produced By Segmental Spinal Nerve Ligation İn TheRat. Pain,1992. 50: p. 355- 363.
Jaggi, A.S., V. Jain, N. Singh,Animalmodels of neuropathicpain. Fundam ClinPharmacol, 2011. 25(1): p. 1-28.
Kinnman, E., J.D. Levine, Sensory and sympatheticcontributionsto nevre injury-induced sensoryab normalities in therat. Neuroscience, 1995. 64(3): p. 751-67.
La Buda, C.J., and P.J. Little, Pharmacologicalevaluation of theselectivespinal nevre ligation model of neuropathicpain in therat. J NeurosciMethods, 2005. 144(2): p. 175-81.
Yezierski,R.P, and S.H. Park, Themechanosensitivity of spinal sensory neurons following intra spinal injections of quisqualicacid in therat.NeurosciLett, 1993. 157: p. 115-119.
Kumar, A. H.Kaur, and A. Singh, Neuropathic pain model scaused by damageto central or peripheral nervous system. PharmacolRep, 2018. 70(2): p. 206-16.
Allen, A.R., Surgery of experimentallesion of spinal corde quivalent tocrushin jury of fracturedislocation of spinalcolumn. J AmMedAssoc, 1911. p. 57.
Siddall, P.J., C.L.Xu, and M.J. Cousins, Allodynia following traumatic spinal cordinjury in therat. Neuroreport, 1995. 6(9): p. 1241-4.
Drew, G.M., P.J. Siddall, and A.W. Duggan, Responses of spinal neuron stocutaneous and dorsal rootstimuli in rats with mechanical all odynia after contusive spinal cordinjury. Brain Res, 2001. 893(1-2): p. 59-69.
Watson, B.D., et al., Photochemicallyin duced spinal cordin jury in therat. Brain Res, 1986. 367(1-2): p. 296-300.
Gaviria, M., et al., A mouse model of acuteischemic spinal cordinjury. J Neurotrauma, 2002. 19(2): p. 205-21.
Prado, R.,et al., Photochemicallyinducedgradedspinalcordinfarction. Behavioral, electrophysiological, andmorphologicalcorrelates. J Neurosurg, 1987. 67(5): p. 745-53.
Xu, X.J., et al., Wiesenfeld-Hallin Z. Chronicpain-relatedsyndrome in ratsafterischemicspinalcordlesion: a possibleanimal model forpain in patientswithspinalcordinjury. Pain, 1992. 48(2): p. 279-90.
Hao, J.X., et al., Photochemically induced transient spinalis chemiainduces behavioral hyper sensitivity tomechanical and cold stimuli, but not tonoxious-heatstimuli, in therat. ExpNeurol, 1992. 118(2): p. 187-94.
Christensen, M.D., et al., Mechanical and thermal allodynia in chronic central pain following spinal cord injury. Pain, 1996. 68(1): p. 97-107.
Kim, J., et al., Cold and mechanical allodynia in both hind paws and tail following thoracic spinal cord hemisection in rats: Time courses and their correlates. Neurosci Lett, 2003. 343(3): p. 200-4.
Klit, H., N.B. Finnerup, and T.S. Jensen, Central post-strokepain: clinicalcharacteristics, pathophysiology, andmanagement.LancetNeurol, 2009. (8): p. 857–868.
Lu, H.F., et al., A newcentral post-strokepainrat model: autologous bloodin jectedt halamic hemorrhagein volvedin creased expression of P2X4 receptor.Neurosci. Lett, 2018. 687: p. 124–130.
Gritsch, S., et al., Functionalcharacterization of a mouse model forcentral post-strokepain. MolecularPain, 2016. 12: 1744806916629049.
Dickinson, B. D., et al., Maldynia: Pathophysiologyandmanagement of neuropathicandmaladaptive pain—A report of the AMA Council on ScienceandPublicHealth. PainMedicine, 2010. 11(11): p. 1635-1653.
Authier, N., et al., Assessment of allodynia and hyperalgesia after cisplatin administration to rats.Neurosci Lett, 2000. 291: p. 73-76.
Pennypacker, S.D., et al., Methodsand protocols for chemo therapy-inducedperipheral neuropathy (CIPN) Mouse model susingp aclitaxel. Methods in Cell Biology, Academic PressInc., 2022.
Aley, K.O., D.B. Reichling, and J.D. Levine, Vincristinehyperalgesia in therat: a model of pain fulvincristine neuropathy in humans. Neuroscience, 1996. 73: p. 259–265.
Authier, N., et al., Description of a short-termtaxol-induced nociceptive neuropathy in rats. Brain Res, 2000. 887: p. 239–249.
Ledeboer, A., et al., Intrathecal interleukin-10 gene therapy attenuatespaclitaxelinduced mechanicalal lodyniaandproinflammatorycytokine expression in dorsal rootganglia in rats. Brain BehavImmun, 2007. 21(5): p. 686-98.
Flatters, S.J., and G.J. Bennett, Studies of peripheralsensorynerves in paclitaxelinducedpainfulperipheralneuropathy: Evidenceformitochondrialdysfunction. Pain, 2006. 122(3): p. 245-57.
Polomano, R.C., et al., A painfulperipheralneuropathy in theratp roduced by theche mother apeuticdrug, paclitaxel. Pain, 2001. 94(3): p. 293-304.
Ledeboer, A., et al., Intrathecal interleukin-10 gene therapyattenuatespaclitaxel-inducedmechanicalallodyniaandproinflammatorycytokineexpression in dorsalrootganglia in rats. Brain BehavImmun, 2007. 21(5): p. 686-98.
Argyriou, A.A., et al., Chemotherapy-inducedperipheralneuropathy in adults: A comprehensiveupdate of the literatüre. CancerManagRes, 2014. 6: p. 135-47.
Cece, R., et al., An ultrastructuralstudy of neuronalchanges in dorsalrootganglia (DRG) of ratsafterchroniccisplatinadministrations.HistolHistopathol, 1995. 10(4): p. 837-45
Vera, G., et al., WIN 55,212-2 preventsmechanicalallodynia but not alterations in feedingbehaviourinducedbychroniccisplatin in therat. Life Sci, 2007. 81(6): p.468-79.
Grolleau, F., et al., A possibleexplanationfor a neurotoxiceffect of theanticanceragentoxaliplatin on neuronalvoltage-gatedsodiumchannels. Journal of Neurophysiology, 2001. 85(5): p. 2293-2297.
Joseph, E.K., et al., Sexualdimorphismfor protein kinase C epsilon signaling in a rat model of vincristine-inducedpainfulperipheralneuropathy.Neuroscience, 2003. 119(3): p. 831-8.
Tanner, K.D., J.D. Levine, and K.S. Topp, Microtubuledisorientationandaxonalswelling in unmyelinatedsensoryaxonsduringvincristine-inducedpainfulneuropathy in rat. J CompNeurol, 1998. 395(4): p. 481-92.
Sweitzer, S.M., J.L. Pahl, and J.A. DeLeo, Propentofyllineattenuatesvincristine-inducedperipheralneuropathy in therat. NeurosciLett, 2006. 400(3): p. 258-61.
Tappe-Theodor, A., and R. Kuner, Studyingongoingandspontaneouspain in rodents–challengesandopportunities. Eur. J. Neurosci. 2014. 39: p. 1881–1890.
Bhangoo, S.K., et al., CXCR4 chemokinereceptorsignalingmediatespainhypersensitivity in associationwithantiretroviraltoxicneuropathy. Brain Behav. Immun, 2007. 21: p. 581–591.
Hicks, C.W., and E. Selvin, Epidemiology of peripheralneuropathyandLowerextremitydisease in diabetes. Curr. Diab. Rep, 2019. 19: p. 86.
Biessels, G. J., et al., Phenotypinganimalmodels of diabeticneuropathy: a consensusstatement of thediabeticneuropathystudygroup of the EASD (Neurodiab). Journal of thePeripheralNervousSystem, 2014. 19(2): p. 77-87.
Olukman, M., et al., Treatmentwith NADPH oxidaseinhibitorapocyninalleviatesdiabeticneuropathicpain in rats.NeuralRegenRes, 2018. 13(9): p. 1657-64.
Aley, K.O.,and J.D. Levine, Rapidonsetpaininducedbyintravenousstreptozotocin in therat. J Pain, 2001. 2(3): p. 146-50.
Zhu, Y.F., et al., Rat model of cancer-induced bone pain: changes in nonnociceptivesensoryneurons in vivo. Painreports, 2017. 2(4): p. e603.
Vecht, C.J., Cancerpain: a neurologicalperspective.Curr. Opin. Neurol, 2000. 13: p. 649–653.
Shimoyama, M., et al., A mouse model of neuropathiccancerpain. Pain, 2002. 99: p. 167–174.
Elramah, S., et al., Spinal miRNA-124 regulatessynaptopodinandnociception in an animal model of bone cancerpain. Scientificreports, 2017. 7(1): p. 1-13.
Bandera, A., et al., HIV-associatedneurocognitiveimpairment in the modern ART era: areweclosetodiscoveringreliablebiomarkers in thesetting of virologicalsuppression?. Frontiers in agingneuroscience, 2019. 187.
Burdo, T.H., and A.D. Miller, Animalmodels of HIV peripheralneuropathy.FutureVirol, 2014. 9: p. 465–474.
Herzberg, U.,and J. Sagen,Peripheralnerveexposureto HIV viralenvelope protein gp120 inducesneuropathicpainandspinalgliosis. J Neuroimmunol, 2001. 116(1): p. 29-39.
Cao, L., et al., Murineimmunodeficiencyvirus-inducedperipheralneuropathyandtheassociatedcytokineresponses. J. Immunol, 2012. 189: p. 3724–3733
Valek, L., G. Auburger, and I. Tegeder, Sensoryneuropathyandnociception in rodentmodels of Parkinson'sdisease. DiseaseModels&Mechanisms, 2019. 12(6): p. dmm039396.
Faivre, F., et al., Thehiddenside of Parkinson’sdisease: Studyingpain, anxietyanddepression in animalmodels. Neuroscience&BiobehavioralReviews, 2019. 96: p. 335-352.
Charles, K. A., et al., Alteration of nociceptiveintegration in thespinalcord of a rat model of Parkinson'sdisease. MovementDisorders, 2018. 33(6): p. 1010-1015.
Dina, O.A., et al., Key role forthe epsilon isoform of protein kinase C in painfulalcoholicneuropathy in therat. J Neurosci, 2000. 20(22): p. 8614-9.
Sereda, M.W., Therapeuticadministration of progesterone antagonist in a model of Charcot-Marie-Toothdisease (CMT-1A). NatMed, 2003. 9: p. 1533–1537.
MeyerzuHorste, G, et al., Antiprogesteronetherapyuncouplesaxonallossfromdemyelination in a transgenicrat model of CMT1A neuropathy.AnnNeurol, 2007. 61: p. 61–72.
Kankowski, S., C. Grothe, and K. Haastert‐Talini, Neuropathicpain: Spotlightinganatomy, experimentalmodels, mechanisms, andtherapeuticaspects. EuropeanJournal of Neuroscience, 2021. 54(2): p. 4475-4496.
Sewell, R.D., Neuropathic pain models and outcome measures: a dual translational challenge. Annals of Translational Medicine, 2018. 6(Suppl 1).
Deuis, J. R., et al., Methods used to evaluate pain behaviors in rodents. Frontiers in molecular neuroscience, 2017: 284.
Tjolsen, A., et al., An improved method for tail-flick testing with adjustment for tail-skin temperature. J Neurosci Methods, 1989. 26: p. 259-265.
Dzoyem, J. P., et al., Anti-inflammatory and anti-nociceptive activities of African medicinal spices and vegetables. In Medicinal spices and vegetables from Africa. Academic Press, 2017: p. 239-270.
Bannon, A.W., and A.B., Malmberg,. Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. Current Protocols in Neuroscience, 2007. 41(1): p. 1- 16.
