Korean J Pain.  2021 Oct;34(4):394-404. 10.3344/kjp.2021.34.4.394.

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

• Lee HJ
• Ju J
• Choi E
• Nahm FS
• Choe GY
• Lee PB

• KMID: 2520747
• DOI: http://doi.org/10.3344/kjp.2021.34.4.394

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.

Keyword

Chronic Pain; Constriction; Pathologic; Fibrosis; Hyperalgesia; Inflammation; Injections; Epidural; Low Back Pain; Polydeoxyribonucleotides; Radiculopathy; Receptor; Adenosine A2A; Spinal Stenosis

Figure

• 

  Fig. 1 Timeline of the experimental protocol. S: sham, V: vehicle, 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: 3,7-dimethyl-1-propargylxanthine, PDDM: epidural PDRN 8 mg/kg + epidural DMPX 0.1 mg/kg, LFS: lumbar foraminal stenosis, DRG: dorsal root ganglion.

• 

  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.

• 

  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.

• 

  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).

• 

  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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