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

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 A 2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.

Comparison of ligamentum flavum thickness between central and lateral lesions in a patient with central lumbar spinal canal stenosis

“…Second, several different methods have been shown to be effective in discriminating spinal stenosis to evaluate lumbar spinal stenosis, such as sedimentation sign and morphologic grade system. [23][24][25][26][27][28][29][30] However, we only measured CLFT and LLFT. Thus, our research might have some limitations regarding measurement of morphologic change and epidural pressure.…”

Epidural and Intrathecal Drug Delivery in Rats and Mice for Experimental Research: Fundamental Concepts, Techniques, Precaution, and Application

“…Therefore, the applications of direct epidural injections using needle puncture in mice and rats are limited because the needle can easily penetrate the dura mater and enter the intrathecal space. Therefore, intrathecal injection by acute needle puncture [5,6,17], intrathecal catheterization [11,13,14], and epidural catheterization [2][3][4] but not epidural injection by needle puncture is frequently used in mice and rats.…”

“…To solve this problem, the dead space can first be filled with the injected agent, and the targeted volume should then be withdrawn in the syringe and then injected. Another method is by flushing with an equal volume of saline to replace the dead space occupied by the drugs [3,14,18]. However, care should be taken to prevent air bubbles when changing the syringe, which may cause adverse effects such as the alteration of subarachnoid pressure and injury to the nerves or meninges [55].…”

“…However, beyond pain management, the intrathe-cal route is widely used for stem cell therapy [45,46,62,67,68], gene therapy [7,17,38,68], delivery of immune cells [63], sedation [41], protein therapy, insulin delivery [69], mineral delivery [70], chemical delivery [2,[70][71][72], and drug therapy using agonists [43,72,73], antagonists [43,64], antibiotics [70,74], and antiparasitic drugs [75] (Table 6). Intraspinal injection used in pain models can be divided into cancer pain models [68], including chemotherapy, induced pain models [5,75], and non-cancer pain models, such as models of arthritis [24], rheumatoid arthritis [72], diabetes-induced neuropathic pain [69,73], chronic pancreatitis-induced pain [19], spinal injury-induced pain [57,60], post-herpetic neuralgia [43], foraminal stenosis-induced pain [2,3], chronic DRG compression-induced pain [45], spared nerve injury [76], intrathecal capsaicin-induced spontaneous pain [71], chronic post-ischemia neuropathic pain…”

“…To overcome these par-enteral delivery challenges, intraspinal drug delivery systems are one of the most common approaches used. The epidural [2][3][4] and intrathecal routes [5][6][7] are the most used intraspinal drug delivery routes in rats and mice. The target of each drug delivery route is the cerebrospinal fluid (CSF).…”