Danggui Sini Decoction Alleviates Sciatica by Reducing Peripheral Sensitization through Downregulation of Transient
Di Zhang1, Zi-Feng Zhuang1, Shao-Zi Lin1
1College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Objective:
To elucidate whether Danggui Sini Decoction (DGSD) relieves sciatica by downregulating transient receptor potential (TRP) channels involved in peripheral sensitization.
Methods:
After conducting chronic constriction injury of sciatic nerve (CCI) operation, 32 SD rats, randomly assigned to the sham, CCI 7d, CCI 14d, and CCI 21d groups (n=8 per group), were used to observe the course of sciatica. mRNA sequencing of dorsal root ganglia (DRG) was conducted on rats in the sham and CCI 21d groups. Another 32 rats were divided into the sham, CCI, mecobalamin, and DGSD groups, 8 in each group. mRNA sequencing analysis and single-cell RNA-sequencing (scRNA-seq) data analysis were conducted. Behavioural tests were conducted to evaluate the therapeutic effects of DGSD. The levels of TRP vanilloid (TRPV)1-4, TRP ankyrin 1 (TRPA1), TRP melastatin 8 (TRPM8), Ras homolog family member A (RhoA), and phosphorylated p38 mitogen-activated protein kinase (p-p38MAPK) were measured via Western blot, and the serum levels of C-C motif chemokine ligand 2 and 5 (CCL2, CCL5), substance P (SP), and prostaglandin E2 (PGE2) were conducted via ELISA.
Results:
scRNA-seq and mRNA sequencing analysis revealed that inflammatory mediator regulation of TRP channels played a role in the development of sciatica. CCI rats exhibited cold hyperalgesia from day 4 to 21, increased the DRG protein expression levels of TRP channels, including TRPV1-4, TRPA1, TRPM8, RhoA, p-p38MAPK, CCL2, CCL5, SP, and PGE2. Treatment with DGSD decreased the serum levels of CCL2, CCL5, SP, and PGE2, and reduced the levels of RhoA, p-p38MAPK, TRPV1-4, TRPA1, and TRPM8 in DRG (P<0.05).
Conclusion:
CCI increased the levels of TRP channels and inflammatory factors, inducing cold hyperalgesia, whereas DGSD relieved pain via inhibiting peripheral sensitization to relieve cold hyperalgesia by reducing the inflammatory factors and TRP.