Korean J Pain.  2021 Oct;34(4):405-416. 10.3344/kjp.2021.34.4.405.

Sec-O-glucosylhamaudol mitigates inflammatory processes and autophagy via p38/JNK MAPK signaling in a rat neuropathic pain model

Affiliations
  • 1School of Medicine, Chosun University, Gwangju, Korea
  • 2Department of Anesthesiology and Pain Medicine, Chosun University Hospital, Gwangju, Korea
  • 3Department of Anesthesiology and Pain Medicine, School of Medicine, Chosun University, Gwangju, Korea
  • 4Cardiovascular Reseach Center, Massachusetts General Hospital, Boston, MA, USA

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 μg/day; and Group SOG192, SOG at 192 μg/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.

Keyword

Analgesia; Autophagy; Biological Products; Cytokines; Hyperalgesia; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Neuralgia; NFkappa B; Pain
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