Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis
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Background: We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). Methods: This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/ kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. Results: A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. Conclusions: Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.
Abstract
Background: We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). Methods: This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/ kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. Results: A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. Conclusions: Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.
참고문헌 (43)
- Lurie J, "Management of lumbar spinal stenosis", BMJ, 352, pp.h6234~ (2016)
- Costandi S, "Lumbar spinal stenosis : therapeutic options review", Pain Pract, 15, pp.68~81 (2015)
- Deyo RA, "Treatment of lumbar spinal stenosis : a balancing act", Spine J, 10, pp.625~627 (2010)
- Chad DA, "Lumbar spinal stenosis", Neurol Clin, 25, pp.407~418 (2007)
- Watanabe R, "Vascular and neural pathology of lumbosacral spinal stenosis", J Neurosurg, 64, pp.64~70 (1986)
- Binder DK, "Lumbar spinal stenosis", Semin Neurol, 22, pp.157~166 (2002)
- Albrecht DS, "Neuroinflammation of the spinal cord and nerve roots in chronic radicular pain patients", Pain, 159, pp.968~977 (2018)
- Cipriano PW, "18F-FDG PET", MRI in chronic sciatica : early results revealing spinal and nonspinal abnormalities, 2018, pp.59, 967~972
- Squadrito F, "Pharmacological activity and clinical use of PDRN", Front Pharmacol, 8, pp.224~ (2017)
- Kang KN, "Effect of transforaminal epidural polydeoxyribonucleotide injections on lumbosacral radiculopathy: a case report", Medicine (Baltimore), 96, pp.e7174~ (2017)
- Park D, "Application of ultrasound-guided C5 nerve root block using polydeoxyribonucleotide in traumatic C5 nerve root injury caused by fracture of the articular process of the cervical spine: a case report", Medicine (Baltimore), 96, pp.e8728~ (2017)
- Kilkenny C, "Animal research : reporting in vivo experiments : the ARRIVE guidelines", Br J Pharmacol, 160, pp.1577~1579 (2010)
- 박상현, "Therapeutic Effect of Epidurally Administered Lipo-Prostaglandin E1 Agonist in a Rat Spinal Stenosis Model", The Korean Journal of Pain, 27(3), pp.219~228 (2014), 대한통증학회
- Nahm FS, "Therapeutic effect of epidural hyaluronic acid in a rat model of foraminal stenosis", J Pain Res, 10, pp.241~248 (2017)
- Ikawa M, "Ectopic firing due to artificial venous stasis in rat lumbar spinal canal stenosis model : a possible pathogenesis of neurogenic intermittent claudication", Spine (Phila Pa 1976), 30, pp.2393~2397 (2005)
- Charan J, "How to calculate sample size in animal studies?", J Pharmacol Pharmacother, 4, pp.303~306 (2013)
- Hu SJ, "An experimental model for chronic compression of dorsal root ganglion produced by intervertebral foramen stenosis in the rat", Pain, 77, pp.15~23 (1998)
- Choi SS, "The neurological safety of epidural gabapentin in rats : a light microscopic examination", Anesth Analg, 101, pp.1422~1426 (2005)
- Bitto A, "Polydeoxyribonucleotide(PDRN)restores blood flow in an experimental model of peripheral artery occlusive disease", J Vasc Surg, 48, pp.1292~1300 (2008)
- Dixon WJ, "Efficient analysis of experimental observations", Annu Rev Pharmacol Toxicol, 20, pp.441~462 (1980)
- Chaplan SR, "Quantitative assessment of tactile allodynia in the rat paw", J Neurosci Methods, 53, pp.55~63 (1994)
- Kawakami M, "Epidural injection of cyclooxygenase-2 inhibitor attenuates pain-related behavior following application of nucleus pulposus to the nerve root in the rat", J Orthop Res, 20, pp.376~381 (2002)
- Nakai K, "The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model", Anesth Analg, 94, pp.1537~1541 (2002)
- Dunn OJ, "Multiple comparisons among means", J Am Stat Assoc, 56, pp.52~64 (1961)
- Kaelin-Lang A, "Expression of adenosine A2a receptor gene in rat dorsal root and autonomic ganglia", Neurosci Lett, 246, pp.21~24 (1998)
- Sawynok J, "Adenosine receptor targets for pain", Neuroscience, 338, pp.1~18 (2016)
- Daré E, "Modulation of glial cell functions by adenosine receptors", Physiol Behav, 92, pp.15~20 (2007)
- Lee SH, "Antiallodynic effects of polydeoxyribonucleotide in an animal model of neuropathic pain and complex regional pain syndrome", J Korean Med Sci, 35, pp.e225~ (2020)
- Jirathanathornnukul N, "Increased expression of vascular endothelial growth factor is associated with hypertrophic ligamentum flavum in lumbar spinal canal stenosis", J Investig Med, 64, pp.882~887 (2016)
- Kim SE, "Polydeoxyribonucleotide exerts therapeutic effect by increasing VEGF and inhibiting inflammatory cytokines in ischemic colitis rats", Biomed Res Int, 2020, pp.2169083~ (2020)
- Friedly JL, "A randomized trial of epidural glucocorticoid injections for spinal stenosis", N Engl J Med, 371, pp.11~21 (2014)
- Carreon LY, "Costeffectiveness of lumbar epidural steroid injections", Spine (Phila Pa 1976), 43, pp.35~40 (2018)
- Even JL, "Effects of epidural steroid injections on blood glucose levels in patients with diabetes mellitus", Spine (Phila Pa 1976), 37, pp.E46~E50 (2012)
- Mandel S, "A retrospective analysis of vertebral body fractures following epidural steroid injections", J Bone Joint Surg Am, 95, pp.961~964 (2013)
- Friedly JL, "Systemic effects of epidural steroid injections for spinal stenosis", Pain, 159, pp.876~883 (2018)
- Tuel SM, "Cushing’s syndrome from epidural methylprednisolone", Pain, 40, pp.81~84 (1990)
- Aldrete JA, "Epidural injections of indomethacin for postlaminectomy syndrome : a preliminary report", Anesth Analg, 96, pp.463~468 (2003)
- Freeman BJ, "Randomized, double-blind, placebo-controlled, trial of transforaminal epidural etanercept for the treatment of symptomatic lumbar disc herniation", Spine (Phila Pa 1976), 38, pp.1986~1994 (2013)
- Senocak O, "Motor conduction time along the cauda equina in patients with lumbar spinal stenosis", Spine (Phila Pa 1976), 34, pp.1410~1414 (2009)
- 박지원, "Regenerative Effect of the Polydeoxyribonucleotide after Sciatic Nerve Transection in Mouse", 조직공학과 재생의학, 12(6), pp.457~463 (2015), 한국조직공학과 재생의학회[DOI]
- Galeano M, "Polydeoxyribonucleotide stimulates angiogenesis and wound healing in the genetically diabetic mouse", Wound Repair Regen, 16, pp.208~217 (2008)
- Andreollo NA, "Rat’s age versus human’s age: what is the relationship?", Arq Bras Cir Dig, 25, pp.49~51 (2012)
- Turner PV, "Administration of substances to laboratory animals : routes of administration and factors to consider", J Am Assoc Lab Anim Sci, 50, pp.600~613 (2011)