The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
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Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

  • Oh, Seon Hee (School of Medicine, Chosun University) ;
  • Kim, Suk Whee (Department of Anesthesiology and Pain Medicine, Chosun University Hospital) ;
  • Kim, Dong Joon (Department of Anesthesiology and Pain Medicine, Chosun University Hospital) ;
  • Kim, Sang Hun (Department of Anesthesiology and Pain Medicine, Chosun University Hospital) ;
  • Lim, Kyung Joon (Department of Anesthesiology and Pain Medicine, Chosun University Hospital) ;
  • Lee, Kichang (Cardiovascular Reseach Center, Massachusetts General Hospital) ;
  • Jung, Ki Tae (Department of Anesthesiology and Pain Medicine, Chosun University Hospital)
  • Received : 2021.06.14
  • Accepted : 2021.07.20
  • Published : 2021.10.01
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Abstract

Background: This study investigated the effect of intrathecal Sec-O-glucosylhamaudol (SOG) on the p38/c-Jun N-terminal kinase (JNK) signaling pathways, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-related inflammatory responses, and autophagy in a spinal nerve ligation (SNL)-induced neuropathic pain model. Methods: The continuous administration of intrathecal SOG via an osmotic pump was performed on male Sprague-Dawley rats (n = 50) with SNL-induced neuropathic pain. Rats were randomized into four groups after the 7th day following SNL and treated for 2 weeks as follows (each n = 10): Group S, sham-operated; Group D, 70% dimethylsulfoxide; Group SOG96, SOG at 96 ㎍/day; and Group SOG192, SOG at 192 ㎍/day. The paw withdrawal threshold (PWT) test was performed to assess neuropathic pain. Western blotting of the spinal cord (L5) was performed to measure changes in the expression of signaling pathway components, cytokines, and autophagy. Additional studies with naloxone challenge (n = 10) and cells were carried out to evaluate the potential mechanisms underlying the effects of SOG. Results: Continuous intrathecal SOG administration increased the PWT with p38/JNK mitogen-activated protein kinase (MAPK) pathway and NF-κB signaling pathway inhibition, which induced a reduction in proinflammatory cytokines with the concomitant downregulation of autophagy. Conclusions: SOG alleviates mechanical allodynia, and its mechanism is thought to be related to the regulation of p38/JNK MAPK and NF-κB signaling pathways, associated with autophagy during neuroinflammatory processes after SNL.

Keywords

Acknowledgement

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1C1B5085816).

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