Nöropatik Ağrı Kronik Sıkıştırma Hasarı Modelinde Bir Değişiklik: Krome Katgüt Yerine İpek Kullanımı
Yıl 2024,
Cilt: 26 Sayı: 3, 256 - 262, 24.12.2024
Recep Selim Şentürk
,
Aytül Önal
,
Sibel Ülker Göksel
Öz
Amaç: Kronik konstriksiyon yaralanması (KKY) nöropatik ağrı sıçan modelinde krome katgüt kullanımı yoğun nöroinflamasyona ve ototomi gibi istenmeyen durumlara neden olmaktadır. Bu durum ağrı davranış testlerinin uygulanmasında ve yorumlanmasında zorluklara neden olmaktadır. Bu çalışmada, KKY modelinde cerrahi ipeğin dikiş materyali olarak kullanımının uygunluğunun davranış testleri ve bazı biyobelirteçlere dayalı olarak araştırılması amaçlandı.
Gereç ve Yöntemler: KKY modeli, sıçanların sağ siyatik sinirlerinin cerrahi ipek ile gevşek bir şekilde bağlanmasıyla oluşturuldu. Taktil allodini, termal ve mekanik hiperaljezi ameliyat sonrası 2., 7., 14., 21. ve 29. günlerde değerlendirildi. Glial fibriller asidik protein (GFAP), sinyal dönüştürücü ve transkripsiyon aktivatörü 3 (STAT3) ve bunun fosforile edilmiş formunun (p-STAT3) ekspresyonları, omurilik dokusundan western blot tekniği ile değerlendirildi.
Bulgular: Siyatik siniri bağlanan sıçanlar kilo kaybetmedi, ancak kontrol sıçanları gibi 14, 21 ve 29. günlerde kilo aldı. Operasyon sonrası üç farklı ağrı testinde ağrı eşiklerinde istatistiksel olarak anlamlı düşüşler saptandı. Ağrı eşiğindeki azalmaya, aynı anda 2. ve 14. günlerde omurilikteki GFAP protein ekspresyonunda istatistiksel olarak anlamlı bir artış eşlik etti. Omurilikte STAT3 veya p-STAT3 proteininin ekspresyonunda herhangi bir zamanda istatistiksel olarak anlamlı bir fark bulunmadı.
Sonuç: Klasik KKY modelinden beklenen kilo kaybı ve ototomi olmaması, ağrı eşiğindeki düşüşün tersine dönmesi, buna eşlik eden omurilikte GFAP protein ekspresyonunda artış, STAT3 ve p-STAT3 ekspresyonunda değişiklik olmaması çalışmamızda siyatik sinir üzerine 3 adet gevşek ipek düğüm atarak oluşturduğumuz modelde nöroinflamasyonun daha hafif seyrettiğini göstermektedir.
Proje Numarası
EGE ÜNİVERSİTESİ BAP 18-TIP-029.
Kaynakça
- Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: Clinical manifestations and
mechanisms. Lancet Neurol. 2014;13(9):924-935.
- Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33(1):87-107.
- Austin PJ, Wu A, Moalem-Taylor G. Chronic constriction of the sciatic nerve and pain hypersensitivity testing in rats. J Vis Exp. 2012;61:e3391.
- Jaggi AS, Jain V, Singh N. Animal models of neuropathic pain. Fundam Clin Pharmacol. 2011;25(1):1-28.
- van der Wal SE, Cornelissen L, Behet MC, Vaneker M, Steegers MA, Vissers KC. Behavior of neuropathic pain in
mice following chronic constriction injury comparing silk and catgut ligatures. SpringerPlus. 2015;4:225.
- Gao YJ, Ji RR. Targeting astrocyte signaling for chronic pain. Neurotherap. 2010;7(4):482-493.
- Ji RR, Berta T, Nedergaard M. Glia and pain: Is chronic pain a gliopathy? Pain. 2013;154(Suppl 1):10-28.
- Garrison CJ, Dougherty PM, Kajander KC, Carlton SM. Staining of glial fibrillary acidic protein (GFAP) in lumbar
spinal cord increases following a sciatic nerve constriction injury. Brain Res. 1991;565(1):1-7.
- Gomes FC, Paulin D, Moura Neto V. Glial fibrillary acidic protein (GFAP): Modulation by growth factors and its
implication in astrocyte differentiation. Braz J Med Biol Res. 1999;32(5):619-631.
- Zhang S, Wu M, Peng C, Zhao G, Gu R. GFAP expression in injured astrocytes in rats. Exp Ther Med. 2017;14(3):1905-1908.
- Dominguez E, Rivat C, Pommier B, Mauborgne A, Pohl M. JAK/STAT3 pathway is activated in spinal cord
microglia after peripheral nerve injury and contributes to neuropathic pain development in rat. J Neurochem.
2008;107(1):50-60.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem.
1951;193(1):265-275.
- Medeiros P, dos Santos IR, Júnior IM, et al. An adapted chronic constriction injury of the sciatic nerve produces
sensory, affective, and cognitive impairments: A peripheral mononeuropathy model for the study of comorbid neuropsychiatric disorders associated with neuropathic pain in rats. Pain Med. 2021;22(2):338-351.
- Attal N, Jazat F, Kayser V, Guilbaud G. Further evidence for 'pain-related' behaviours in a model of unilateral
peripheral mononeuropathy. Pain. 1990;41(2):235-251.
- Robinson I, Meert TF. Stability of neuropathic pain symptoms in partial sciatic nerve ligation in rats is affected
by suture material. Neurosci Lett. 2005;373(2):125-129.
- Odem MA, Lacagnina MJ, Katzen SL, Li J, Spence EA, Grace PM. Sham surgeries for central and peripheral
neural injuries persistently enhance pain-avoidance behavior as revealed by an operant conflict test. Pain.
2019;160(1):2440-2450.
- Svíženská IH, Brázda V, Klusáková I, Dubový P. Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root ganglia of a rat neuropathic pain model. J Histochem Cytochem. 2013;61(7):529-547.
- Romero-Sandoval A, Chai N, Nutile-McMenemy N, DeLeo JA. A comparison of spinal Iba1 and GFAP
expression in rodent models of acute and chronic pain. Brain Res. 2008;1219:116-126.
- Tanga FY, Raghavendra V, DeLeo JA. Quantitative realtime RT-PCR assessment of spinal microglial and
astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int. 2004;45(2-3):397-407.
- Tsuda M, Kohro Y, Yano T, et al. JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic
pain maintenance in rats. Brain. 2011;134:1127-1139.
- Dominguez E, Mauborgne A, Mallet J, Desclaux M, Pohl M. SOCS3-mediated blockade of JAK/STAT3 signaling
pathway reveals its major contribution to spinal cord neuroinflammation and mechanical allodynia after
peripheral nerve injury. J Neurosci. 2010;30(16):5754-5766.
A MODIFICATION OF THE CHRONIC CONSTRICTION INJURY MODEL OF NEUROPATHIC PAIN: SILK USAGE INSTEAD OF CHROMIC CATGUT
Yıl 2024,
Cilt: 26 Sayı: 3, 256 - 262, 24.12.2024
Recep Selim Şentürk
,
Aytül Önal
,
Sibel Ülker Göksel
Öz
Objective: In the chronic constriction injury (CCI) neuropathic pain rat model, usage of chromic catgut causes intense neuroinflammation and also undesirable conditions such as autotomy. This causes difficulties in the application and interpretation of pain behaviour tests. In this study, it was aimed to investigate the suitability of the use of surgical silk as a suture material in the CCI model, based on behavioural tests and certain biomarkers.
Material and Methods: CCI model was created by loosely ligating the right sciatic nerves of rats with surgical silk. Tactile allodynia, thermal and mechanical hyperalgesia were evaluated on the 2nd, 7th, 14th, 21st and 29th postoperative days. Expressions of glial fibrillary acidic protein (GFAP), signal transducer and transcription activator 3 (STAT3) and its phosphorylated form (p-STAT3) were evaluated from the spinal cord tissue by western blotting technique.
Results: Sciatic nerve-ligated rats did not lose weight but gained weight on days 14, 21, and 29 like control rats. Statistically significant decreases were found in pain thresholds in three different pain tests after the operation. The decrease in the pain threshold was accompanied by a statistically significant increase in GFAP protein expression in the spinal cord on days 2 and 14 simultaneously. No statistically significant difference was found in the expression of STAT3 or p-STAT3 protein in the spinal cord at any time.
Conclusion: The absence of weight loss and autotomy expected from the classical CCI model, the reversal of the decrease in the pain threshold, the concomittant increase in GFAP protein expression in the spinal cord, and the absence of change in STAT3 and p-STAT3 expression in our study suggest that the model we created by tying 3 loose silk knots on the sciatic nerve has a milder course of neuroinflammation.
Etik Beyan
The study protocol was approved by the Ege University Faculty of Medicine Local Animal Ethics Committee (2017-028).
Destekleyen Kurum
EGE ÜNİVERSİTESİ REKTÖRLÜĞÜ BAP KOMİSYONU
Proje Numarası
EGE ÜNİVERSİTESİ BAP 18-TIP-029.
Teşekkür
ACKNOWLEDGMENTS: We would like to thank SemraÖzgül from Ege University Faculty of Medicine, Department of Medical Statistics for statistical evaluations and Gürhan Mutlu from Ege University Faculty of Medicine, Department of Medical Pharmacology for technical assistance, CumhurGündüz from Ege University Faculty of Medicine, Department of Medical Biology for contributions to Western Blot analysis.
Kaynakça
- Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: Clinical manifestations and
mechanisms. Lancet Neurol. 2014;13(9):924-935.
- Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33(1):87-107.
- Austin PJ, Wu A, Moalem-Taylor G. Chronic constriction of the sciatic nerve and pain hypersensitivity testing in rats. J Vis Exp. 2012;61:e3391.
- Jaggi AS, Jain V, Singh N. Animal models of neuropathic pain. Fundam Clin Pharmacol. 2011;25(1):1-28.
- van der Wal SE, Cornelissen L, Behet MC, Vaneker M, Steegers MA, Vissers KC. Behavior of neuropathic pain in
mice following chronic constriction injury comparing silk and catgut ligatures. SpringerPlus. 2015;4:225.
- Gao YJ, Ji RR. Targeting astrocyte signaling for chronic pain. Neurotherap. 2010;7(4):482-493.
- Ji RR, Berta T, Nedergaard M. Glia and pain: Is chronic pain a gliopathy? Pain. 2013;154(Suppl 1):10-28.
- Garrison CJ, Dougherty PM, Kajander KC, Carlton SM. Staining of glial fibrillary acidic protein (GFAP) in lumbar
spinal cord increases following a sciatic nerve constriction injury. Brain Res. 1991;565(1):1-7.
- Gomes FC, Paulin D, Moura Neto V. Glial fibrillary acidic protein (GFAP): Modulation by growth factors and its
implication in astrocyte differentiation. Braz J Med Biol Res. 1999;32(5):619-631.
- Zhang S, Wu M, Peng C, Zhao G, Gu R. GFAP expression in injured astrocytes in rats. Exp Ther Med. 2017;14(3):1905-1908.
- Dominguez E, Rivat C, Pommier B, Mauborgne A, Pohl M. JAK/STAT3 pathway is activated in spinal cord
microglia after peripheral nerve injury and contributes to neuropathic pain development in rat. J Neurochem.
2008;107(1):50-60.
- Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem.
1951;193(1):265-275.
- Medeiros P, dos Santos IR, Júnior IM, et al. An adapted chronic constriction injury of the sciatic nerve produces
sensory, affective, and cognitive impairments: A peripheral mononeuropathy model for the study of comorbid neuropsychiatric disorders associated with neuropathic pain in rats. Pain Med. 2021;22(2):338-351.
- Attal N, Jazat F, Kayser V, Guilbaud G. Further evidence for 'pain-related' behaviours in a model of unilateral
peripheral mononeuropathy. Pain. 1990;41(2):235-251.
- Robinson I, Meert TF. Stability of neuropathic pain symptoms in partial sciatic nerve ligation in rats is affected
by suture material. Neurosci Lett. 2005;373(2):125-129.
- Odem MA, Lacagnina MJ, Katzen SL, Li J, Spence EA, Grace PM. Sham surgeries for central and peripheral
neural injuries persistently enhance pain-avoidance behavior as revealed by an operant conflict test. Pain.
2019;160(1):2440-2450.
- Svíženská IH, Brázda V, Klusáková I, Dubový P. Bilateral changes of cannabinoid receptor type 2 protein and mRNA in the dorsal root ganglia of a rat neuropathic pain model. J Histochem Cytochem. 2013;61(7):529-547.
- Romero-Sandoval A, Chai N, Nutile-McMenemy N, DeLeo JA. A comparison of spinal Iba1 and GFAP
expression in rodent models of acute and chronic pain. Brain Res. 2008;1219:116-126.
- Tanga FY, Raghavendra V, DeLeo JA. Quantitative realtime RT-PCR assessment of spinal microglial and
astrocytic activation markers in a rat model of neuropathic pain. Neurochem Int. 2004;45(2-3):397-407.
- Tsuda M, Kohro Y, Yano T, et al. JAK-STAT3 pathway regulates spinal astrocyte proliferation and neuropathic
pain maintenance in rats. Brain. 2011;134:1127-1139.
- Dominguez E, Mauborgne A, Mallet J, Desclaux M, Pohl M. SOCS3-mediated blockade of JAK/STAT3 signaling
pathway reveals its major contribution to spinal cord neuroinflammation and mechanical allodynia after
peripheral nerve injury. J Neurosci. 2010;30(16):5754-5766.