[논문]Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis

Lee, Ho-Jin; Ju, Jiyoun; Choi, Eunjoo; Nahm, Francis Sahngun; Choe, Ghee Young; Lee, Pyung Bok

doi:10.3344/kjp.2021.34.4.394

Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis 원문보기

The Korean journal of pain, v.34 no.4, 2021년, pp.394 - 404

Lee, Ho-Jin (Department of Anesthesiology and Pain Medicine, Seoul National University Hospital) , Ju, Jiyoun (Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital) , Choi, Eunjoo (Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine) , Nahm, Francis Sahngun (Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine) , Choe, Ghee Young (Department of Pathology, Seoul National University Bundang Hospital) , Lee, Pyung Bok (Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine)

Abstract ▼ AI-Helper

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.

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표/그림 (9)

표 Table 1. Drugs, dosage, administration route, presence of spinal stenosis model and presence of epidural catheter per group
그림 Fig. 1. Timeline of the experimentalFollow-up behavioral tests protocol. S: sham, V: vehicle, P5: epiduralVon Frey test (Day 9, 13, 20, 27) polydeoxyribonucleotide (PDRN) 5 mg/Treadmill test (Day 13, 20, 27)kg, P8: epidural PDRN 8 mg/kg, P10:epidural PDRN 10 mg/kg, IP: intraperito-Sacrifice(Day 30) neal PDRN 8 mg/kg, DMPX: 3,7-dimethyl-Excluded (n = 4) 1-propargylxanthine, PDDM: epiduralHistopatholoic examination Failed to confirmation PDRN 8 mg/kg + epidural DMPX 0.1 mg/of steel rods in the kg, LFS: lumbar foraminal stenosis, DRG:peri L5-DRG dorsal root ganglion.
그림 Fig. 2. (A) Changes in the mechanical withdrawal threshold compared to contra-lateral paw over time examined using the von Frey test in the first stage. (B) Changes in the mechanical withdrawal threshold compared to contra-lateral paw over time examined using the von Frey test in the second stage. Data presents the mean ± standard error of the mean. The preoperative values (before) and pre-drug postoperative values (baseline) of behavioral tests were calculated as the average value of the results obtained over 3 and 2 consecutive days, respectively. P5: epidural polydeoxyribonucleotide (PDRN) 5 mg/kg, P8: epidural PDRN 8 mg/kg, P10: epidural PDRN 10 mg/kg, IP: intraperitoneal PDRN 8 mg/kg, DMPX: epidural 3,7-dimethyl-1-propargilxanthine (DMPX) 0.1 mg/kg, PDDM: epidural PDRN 8 mg/kg + epidural DMPX 0.1 mg/kg. ^aSignificant at P < 0.05, compared to the baseline within the same group. ^bSignificant at P < 0.05, compared to the DMPX group. ^cSignificant at P < 0.05, compared to the PDDM group. ^dSignificant at P < 0.05, compared to the IP group.
그림 Fig. 3. (A) Changes to the treadmill running time in the first stage. (B) Changes to the treadmill running time in the second stage. Data are presented as the mean ± standard error of the mean. The preoperative values (before) and pre-drug postoperative values (baseline) of the behavioral tests were calculated as the average value of the results obtained over 3 and 2 consecutive days, respectively. P5: epidural polydeoxyribonucleotide (PDRN) 5 mg/kg, P8: epidural PDRN 8 mg/kg, P10: epidural PDRN 10 mg/kg, IP: intraperitoneal PDRN 8 mg/kg, DMPX: epidural 3,7-dimethyl-1-propargilxanthine (DMPX) 0.1 mg/kg, PDDM: epidural PDRN 8 mg/kg + epidural DMPX 0.1 mg/kg. ^aSignificant at P < 0.05, compared to the baseline within the same group. ^bSignificant at P < 0.05, compared to the DMPX group. ^cSignificant at P < 0.05, compared to the PDDM group. ^dSignificant at P < 0.05, compared to the IP group.
표 Table 2. Histologic evaluation of epineurial inflammation in dorsal root ganglion
표 Table 3. Histologic evaluation of epineurial fibrosis in dorsal root ganglion
표 Table 4. Histologic evaluation of chromatolysis in dorsal root ganglion
그림 Fig. 4. Microscopic findings of the left dorsal root ganglia in the vehicle group 24 days after the epidural injection. (A) The dotted circle indicates the location of the steel rod (Hematoxylin and eosin [H&E] stain, ×40). (B) The broad short arrow indicates central chromatolysis and the thin long arrow indicates segmental chromatolysis (H&E stain, ×400).
그림 Fig. 5. Microscopic findings of the left dorsal root ganglia in the vehicle group (A and B) and in the polydeoxyribonucleotide (PDRN) 5 mg/kg group (C and D), 24 days after the epidural injection. (A) Note diffuse and dense infiltration of inflammatory cells (grade 4) in epineurium (red box) (Hematoxylin and eosin [H&E] stain, ×400). (B) Note dense and diffuse fibrosis (grade 4) of epineurium (red box) (H&E stain, ×400). (C) Note no infiltration of inflammatory cells (grade 0) in epineurium (red box) in the PDRN group, in contrast to figure A (H&E stain, ×400). (D) Note minimal fibrosis (grade 0) of epineurium (red box) in the PDRN group, in contrast to figure B (H&E stain, ×200).

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