J Korean Med Sci.  2020 Jul;35(26):e225. 10.3346/jkms.2020.35.e225.

Anti-Allodynic Effects of Polydeoxyribonucleotide in an Animal Model of Neuropathic Pain and Complex Regional Pain Syndrome

• Lee SH
• Yoo SH
• Lee HJ
• Han D
• Lee J
• Jeon SH
• Cho EA
• Park HJ

• KMID: 2503682
• DOI: http://doi.org/10.3346/jkms.2020.35.e225

Abstract

Background
Spinal nerve ligation (SNL) model is one of the representative models of the neuropathic pain model. Neuropathic pain in a chronic post-ischemic pain (CPIP) mimics the symptoms of complex regional pain syndrome (CRPS). The administration of polydeoxyribonucleotide (PDRN), which has regenerative and anti-inflammatory effects, has been studied and is used in clinical practice treating various diseases. However, the analgesic effect of PDRN in a neuropathic pain or CRPS model remains unknown.
Methods
PDRN (3.3, 10, and 20 mg/kg) was administered into the subcutaneous (SC) layer of the hind paws of SNL and CPIP models. Mechanical anti-allodynic effects were then investigated using the von Frey test. In the immunohistochemical examination, dorsal root ganglia (DRG) and the spinal cord were harvested and examined for the expression of glial fibrillary acidic protein (GFAP) after the 20 mg PDRN injection.
Results
Mechanical allodynia was significantly alleviated by administration of PDRN in SNL and CPIP mice at all of the time point. As the dose of PDRN increased, the effect was greater. The 20 mg PDRN injection was found to have the most effective anti-allodynic effect. The increased expression of GFAP in DRG and the spinal cord of SNL and CPIP model decreased following the administration of PDRN than vehicle.
Conclusion
SC administration of PDRN results in the attenuation of allodynia and activation of astrocytes in neuropathic pain or CRPS models. We propose that PDRN can have significant potential advantages in neuropathic pain treatment.

Keyword

Polydeoxyribonucleotide; Neuropathic Pain; Complex Regional Pain Syndrome; Spinal Nerve Ligation Model; Chronic Post-ischemic Pain Model

Figure

• 

  Fig. 1 Time course of mechanical allodynia in the ipsilateral and contralateral hind paw of SNL and control mice, CPIP and control mice as shown via von Frey testing. (A) The withdrawal thresholds of control mice were not significantly changed throughout the 21 days of testing. The withdrawal thresholds of ipsilateral SNL mice paws significantly increased on the fourth day and continued for 21 days after reperfusion. (B) The withdrawal thresholds of control mice were not significantly altered throughout the 21 days of testing. The withdrawal thresholds of ipsilateral CPIP mice were significantly reduced and lasted for 21 days after reperfusion.SNL = spinal nerve ligation, CPIP = chronic post-ischemic pain.*P < 0.05, **P < 0.005, ***P < 0.001 at each time point between control and CPIP mice.

• 

  Fig. 2 The effect of the administration of PDRN on the tactile threshold in SNL and CPIP mice. (A) PDRN injections dose-dependently reduced mechanical allodynia in SNL mice when compared with that in the control group. PDRN 20 mg/kg injection group showed the most effective attenuation of mechanical allodynia. (B) Mechanical allodynia was attenuated in all groups of PDRN injections. The PDRN 20 mg/kg group showed the greatest decrease in mechanical allodynia and remained effective.NS = not significant, PDRN = polydeoxyribonucleotide, SNL = spinal nerve ligation, CPIP = chronic post-ischemic pain.*P < 0.05, **P < 0.005, ***P < 0.001 at each time point compared to that in the vehicle.

• 

  Fig. 3 The effect of subcutaneous PDRN on GFAP expression (luminous green) in DRG and spinal cord of SNL model. Original magnification: ×200. (A) Immunostaining for GFAP in DRG of sham mouse. (B) PDRN-injected SNL mouse. (C) Vehicle-injected SNL mouse. (D) Immunostaining for GFAP in spinal cord of sham mouse. (E) PDRN-injected SNL mouse. (F) Vehicle-injected SNL mouse.PDRN = polydeoxyribonucleotide, GFAP = glial fibrillary acidic protein, DRG = dorsal root ganglia, SNL = spinal nerve ligation.

• 

  Fig. 4 Histogram representing the optical density of GFAP in DRG, spinal cord from sham (n = 4), PDRN-treated SNL mice (n = 6), and vehicle-treated SNL mice (n = 4). The expression of GFAP in the PDRN-treated group (DRG, 64.19 ± 46.21 optical density; spinal cord, 47.35 ± 22.12 optical density) was significantly decreased compared to the vehicle treated group (DRG, 169.13 ± 71.01 optical density; spinal cord, 118.01 ± 50.82 optical density).GFAP = glial fibrillary acidic protein, DRG = dorsal root ganglia, PDRN = polydeoxyribonucleotide, SNL = spinal nerve ligation.

• 

  Fig. 5 The effect of subcutaneous PDRN on GFAP expression (luminous green) in DRG and spinal cord of CPIP model. Original magnification: ×200. (A) Immunostaining for GFAP in DRG of sham mouse. (B) PDRN-injected CPIP mouse. (C) Vehicle-injected CPIP mouse. (D) Immunostaining for GFAP in spinal cord of sham mouse. (E) PDRN-injected CPIP mouse. (F) Vehicle-injected CPIP mouse.PDRN = polydeoxyribonucleotide, GFAP = glial fibrillary acidic protein, DRG = dorsal root ganglia, CPIP = chronic post-ischemic pain.

• 

  Fig. 6 Histogram representing the optical density of GFAP in DRG, spinal cord from sham (n = 4), PDRN-treated CPIP mice (n = 6), and vehicle-treated CPIP mice (n = 4). The expression of GFAP in the PDRN-treated group (DRG, 122.24 ± 78.00 optical density; spinal cord, 39.98 ± 32.34 optical density) was significantly lower than that in the vehicle-treated group (DRG, 253.35 ± 39.23 optical density; spinal cord, 200.23 ± 27.78 optical density).GFAP = glial fibrillary acidic protein, DRG = dorsal root ganglia, CPIP = chronic post-ischemic pain, PDRN = polydeoxyribonucleotide.

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