Comparison of the Effectiveness of Rapamycin and
Gabapentin Treatment in Rats with Induced Sciatic
Nerve Injury

Çolpak, Halis Ali; Ertürk Zararsız, Gözde; Yay, Arzu Hanım; Kumandaş, Sefer; GÜNAY CANPOLAT, DILEK; Önder, Gözde Özge; Canpolat, Mehmet; Yetkin, Mehmet Fatih

doi:10.14744/etd.2021.87405

Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury

Mehmet CANPOLAT, (Erciyes Üniversitesi, Tıp Fakültesi, Nöroloji Pediatri Anabilim Dalı, Kayseri, Türkiye)

Sefer KUMANDAŞ, (Erciyes Üniversitesi, Tıp Fakültesi, Nöroloji Pediatri Anabilim Dalı, Kayseri, Türkiye)

Halis Ali ÇOLPAK, (Alanya Alaaddin Keykubat Üniversitesi, Sözlü ve Çene Cerrahisi, Antalya, Türkiye)

Dilek Günay CANPOLAT, (Erciyes Üniversitesi, Diş Hekimliği Fakültesi, Sözlü ve Çene Cerrahisi, Kayseri, Türkiye)

Gözde Özge ÖNDER, (Erciyes Üniversitesi, Tıp Fakültesi, Embriyoloji ve Histoloji Anabilim Dalı, Kayseri, Türkiye)

Arzu Hanım YAY, (Erciyes Üniversitesi, Tıp Fakültesi, Embriyoloji ve Histoloji Anabilim Dalı, Kayseri, Türkiye)

Mehmet Fatih YETKİN, (Erciyes Üniversitesi, Tıp Fakültesi, Nöroloji Anabilim Dalı, Kayseri, Türkiye)

Gözde Ertürk ZARARSIZ (Erciyes Üniversitesi, Tıp Fakültesi, Biyoistatistik Anabilim Dalı, Kayseri, Türkiye)

Erciyes Medical Journal

11 2

Yıl: 2022 Cilt: 44 Sayı: 1 Sayfa Aralığı: 56 - 62 Metin Dili: İngilizce DOI: 10.14744/etd.2021.87405 İndeks Tarihi: 20-06-2022

Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury

Öz:

Objective: The purpose of this study was to compare the therapeutic effects of gabapentin (GBP) and different doses of rapamycin (RAPA) in an induced sciatic nerve (SN)-injury rat model. Materials and Methods: The study consisted of 7 groups: Control, Sham, High-dose rapamycin (RAPA-H), Low-dose rapamycin (RAPA-L), GBP, DMSO and DMSO+nerve injury (DMSO+NI). Medical treatment was administered intraperitoneally for 30 days after the induction of SN injury. Results: Significant differences (p<0.001 for all) were found in comparisons between the groups in terms of axon diameter, axon number, and neurofilament (NF) and S100 immunointensity. Among the treatment groups, the highest mean axon diameter value, close to that of the Control group, was seen in the RAPA-L group. In terms of axon number, the value closest to that of the Control group was measured in the GBP group. The NF and S100 immunodensity in the RAPA-L group was similar to that of the GBP group. The S100 immunodensity in the RAPA-L group was closest to that of the Control group. The highest conduction velocity and distal latency values were recorded in the RAPA-L group. Conclusion: The histological and electrophysiological findings observed in this study suggest that RAPA-L treatment is a promising alternative to GBP.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. Modrak M, Talukder MAH, Gurgenashvili K, Noble M, Elfar JC. Peripheral nerve injury and myelination: Potential therapeutic strategies. J Neurosci Res 2020; 98(5): 780–95.
2. Canpolat DG, Soylu E, Dogruel F, Kütük N, Ugur F. Comparison of the analgesic effects of pulse radiofrequency and cryoablation in rabbits with mental nerve neuropathic pain. Niger J Clin Pract 2018; 21(5): 585–90.
3. Smith RV, Havens JR, Walsh SL. Gabapentin misuse, abuse and diversion: a systematic review. Addiction 2016; 111(7): 1160–74.
4. Huang Z, Wang W, Ma J, Li B, Chen J, Yang H, et al. mTOR signaling pathway differently regulates central and peripheral axon regeneration. Acta Biochim Biophys Sin (Shanghai) 2017; 49(8): 689–95.
5. Özcan Ö, Dikmen M. mTOR inhibitors in the treatment of cancer. Marmara Pharm J 2015; 19: 290–7.
6. Küçüköner M, Işıkdoğan A. mTOR signaling pathway and mTOR inhibitors in the treatment of cancer. Dicle Med J 2013; 40(1): 156–60.
7. Rangaraju S, Verrier JD, Madorsky I, Nicks J, Dunn WA Jr, Notterpek L. Rapamycin activates autophagy and improves myelination in explant cultures from neuropathic mice. J Neurosci 2010; 30(34): 11388–97.
8. Nicks J, Lee S, Harris A, Falk DJ, Todd AG, Arredondo K, et al. Rapamycin improves peripheral nerve myelination while it fails to benefit neuromuscular performance in neuropathic mice. Neurobiol Dis 2014; 70: 224–36.
9. Seltzer Z, Dubner R, Shir Y. A novel behavioral model of neuropathic pain disorders produced in rats by partial sciatic nerve injury. Pain. 1990; 43(2): 205–18.
10. O’Connor AB. Neuropathic pain: quality-of-life impact, costs and cost effectiveness of therapy. Pharmacoeconomics 2009; 27(2): 95–112.
11. Alles SRA, Smith PA. Etiology and pharmacology of neuropathic pain. Pharmacol Rev 2018; 70(2): 315–47.
12. Kim KH, Seo HJ, Abdi S, Huh B. All about pain pharmacology: what pain physicians should know. Korean J Pain 2020; 33(2): 108–20.
13. Ozbek Z, Aydin HE, Kocman AE, Ozkara E, Sahin E, Bektur E, et al. Neuroprotective effect of genistein in peripheral nerve injury. Turk Neurosurg 2017; 27(5): 816–22.
14. Câmara CC, Araújo CV, de Sousa KKO, Brito GAC, Vale ML, Raposo RDS, et al. Gabapentin attenuates neuropathic pain and improves nerve myelination after chronic sciatic constriction in rats. Neurosci Lett 2015; 607: 52–8.
15. Machado JA, Ghizoni MF, Bertelli J, Teske GC, Teske GC, Martins DF, et al. Stretch-induced nerve injury: a proposed technique for the study of nerve regeneration and evaluation of the influence of gabapentin on this model. Braz J Med Biol Res 2013; 46(11): 929–35.
16. Wong M. Mammalian target of rapamycin (mTOR) pathways in neurological diseases. Biomed J 2013; 36(2): 40–50.
17. Ding T, Zhu C, Yin JB, Zhang T, Lu YC, Ren J, et al. Slow-releasing rapamycin-coated bionic peripheral nerve scaffold promotes the regeneration of rat sciatic nerve after injury. Life Sci 2015; 122: 92–9.
18. Huang HC, Chen L, Zhang HX, Li SF, Liu P, Zhao TY, et al. Autophagy promotes peripheral nerve regeneration and motor recovery following sciatic nerve crush injury in rats. J Mol Neurosci 2016; 58(4): 416–23.
19. Liu F, Zhang H, Zhang K, Wang X, Li S, Yin Y. Rapamycin promotes Schwann cell migration and nerve growth factor secretion. Neural Regen Res 2014; 9(6): 602–9.
20. Hadamitzky M, Herring A, Kirchhof J, Bendix I, Haight MJ, Keyvani K, et al. Repeated systemic treatment with rapamycin affects behavior and amygdala protein expression in rats. Int J Neuropsychopharmacol 2018; 21(6): 592–602.
21. Liu S, Huang L, Geng Y, He J, Chen X, Xu H, et al. Rapamycin inhibits spermatogenesis by changing the autophagy status through suppressing mechanistic target of rapamycin-p70S6 kinase in male rats. Mol Med Rep 2017; 16(4): 4029–37.
22. Karşidağ S, Ozcan A, Sahin S, Karşidağ S, Kabukçuoğlu F, Uğurlu K, et al. Electrophysiologic and histopathologic evaluation of peripheral nerve regeneration at different nerve segments and with different repair techniques. Acta Orthop Traumatol Turc 2008; 42(4): 278–83.
23. Rupp A, Dornseifer U, Fischer A, Schmahl W, Rodenacker K, Jütting U, et al. Electrophysiologic assessment of sciatic nerve regeneration in the rat: surrounding limb muscles feature strongly in recordings from the gastrocnemius muscle. J Neurosci Methods 2007;166(2): 266–77.
24. Farahpour MR, Ghayour SJ. Effect of in situ delivery of acetyl-L-carnitine on peripheral nerve regeneration and functional recovery in transected sciatic nerve in rat. Int J Surg 2014; 12(12): 1409–15.
25. Yuan A, Rao MV, Veeranna, Nixon RA. Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harb Perspect Biol 2017; 9(4): a018309.
26. Bostan H, Cabalar M, Altinay S, Kalkan Y, Tumkaya L, Kanat A, et al. Sciatic nerve injury following analgesic drug injection in rats: A histopathological examination. North Clin Istanb 2018; 5(3): 176–85.
27. Rezajooi K, Pavlides M, Winterbottom J, Stallcup WB, Hamlyn PJ, Lieberman AR, et al. NG2 proteoglycan expression in the peripheral nervous system: upregulation following injury and comparison with CNS lesions. Mol Cell Neurosci 2004; 25(4): 572–84.
28. Hu LN, Tian JX, Gao W, Zhu J, Mou FF, Ye XC, et al. Electroacupuncture and moxibustion promote regeneration of injured sciatic nerve through Schwann cell proliferation and nerve growth factor secretion. Neural Regen Res 2018; 13(3): 477–83.
29. Mohammadi R, Amini K, Abdollahi-Pirbazari M, Yousefi A. Acetyl salicylic acid locally enhances functional recovery after sciatic nerve transection in rat. Neurol Med Chir (Tokyo) 2013; 53(12): 839–46.
30. Kato K, Satoh T. Changes in the concentration of enolase isozymes and S-100 protein in degenerating and regenerating rat sciatic nerve. J Neurochem 1983; 40(4): 1076–81.

APA	Canpolat M, Kumandaş S, Çolpak H, GÜNAY CANPOLAT D, Önder G, Yay A, Yetkin M, Ertürk Zararsız G (2022). Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. , 56 - 62. 10.14744/etd.2021.87405
Chicago	Canpolat Mehmet,Kumandaş Sefer,Çolpak Halis Ali,GÜNAY CANPOLAT DILEK,Önder Gözde Özge,Yay Arzu Hanım,Yetkin Mehmet Fatih,Ertürk Zararsız Gözde Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. (2022): 56 - 62. 10.14744/etd.2021.87405
MLA	Canpolat Mehmet,Kumandaş Sefer,Çolpak Halis Ali,GÜNAY CANPOLAT DILEK,Önder Gözde Özge,Yay Arzu Hanım,Yetkin Mehmet Fatih,Ertürk Zararsız Gözde Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. , 2022, ss.56 - 62. 10.14744/etd.2021.87405
AMA	Canpolat M,Kumandaş S,Çolpak H,GÜNAY CANPOLAT D,Önder G,Yay A,Yetkin M,Ertürk Zararsız G Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. . 2022; 56 - 62. 10.14744/etd.2021.87405
Vancouver	Canpolat M,Kumandaş S,Çolpak H,GÜNAY CANPOLAT D,Önder G,Yay A,Yetkin M,Ertürk Zararsız G Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. . 2022; 56 - 62. 10.14744/etd.2021.87405
IEEE	Canpolat M,Kumandaş S,Çolpak H,GÜNAY CANPOLAT D,Önder G,Yay A,Yetkin M,Ertürk Zararsız G "Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury." , ss.56 - 62, 2022. 10.14744/etd.2021.87405
ISNAD	Canpolat, Mehmet vd. "Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury". (2022), 56-62. https://doi.org/10.14744/etd.2021.87405

APA	Canpolat M, Kumandaş S, Çolpak H, GÜNAY CANPOLAT D, Önder G, Yay A, Yetkin M, Ertürk Zararsız G (2022). Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. Erciyes Medical Journal, 44(1), 56 - 62. 10.14744/etd.2021.87405
Chicago	Canpolat Mehmet,Kumandaş Sefer,Çolpak Halis Ali,GÜNAY CANPOLAT DILEK,Önder Gözde Özge,Yay Arzu Hanım,Yetkin Mehmet Fatih,Ertürk Zararsız Gözde Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. Erciyes Medical Journal 44, no.1 (2022): 56 - 62. 10.14744/etd.2021.87405
MLA	Canpolat Mehmet,Kumandaş Sefer,Çolpak Halis Ali,GÜNAY CANPOLAT DILEK,Önder Gözde Özge,Yay Arzu Hanım,Yetkin Mehmet Fatih,Ertürk Zararsız Gözde Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. Erciyes Medical Journal, vol.44, no.1, 2022, ss.56 - 62. 10.14744/etd.2021.87405
AMA	Canpolat M,Kumandaş S,Çolpak H,GÜNAY CANPOLAT D,Önder G,Yay A,Yetkin M,Ertürk Zararsız G Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. Erciyes Medical Journal. 2022; 44(1): 56 - 62. 10.14744/etd.2021.87405
Vancouver	Canpolat M,Kumandaş S,Çolpak H,GÜNAY CANPOLAT D,Önder G,Yay A,Yetkin M,Ertürk Zararsız G Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury. Erciyes Medical Journal. 2022; 44(1): 56 - 62. 10.14744/etd.2021.87405
IEEE	Canpolat M,Kumandaş S,Çolpak H,GÜNAY CANPOLAT D,Önder G,Yay A,Yetkin M,Ertürk Zararsız G "Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury." Erciyes Medical Journal, 44, ss.56 - 62, 2022. 10.14744/etd.2021.87405
ISNAD	Canpolat, Mehmet vd. "Comparison of the Effectiveness of Rapamycin and Gabapentin Treatment in Rats with Induced Sciatic Nerve Injury". Erciyes Medical Journal 44/1 (2022), 56-62. https://doi.org/10.14744/etd.2021.87405