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Biomed Res Int. 2018 May 17;2018:4670834. doi: 10.1155/2018/4670834. eCollection 2018.

Hydrogen-Rich Saline Activated Autophagy via HIF-1α Pathways in Neuropathic Pain Model.

Author information

1
Pain Management Center, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
2
Central Laboratory, Tianjin Research Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China.
3
Department of Oncology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.
4
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin Research Institute of Anesthesiology, Tianjin 300211, China.

Abstract

Background:

Neuropathic pain is a chronic and intractable pain, with very few effective analgesics. It involves an impaired cell autophagy process. Hydrogen-rich saline (HRS) reportedly reduces allodynia and hyperalgesia in a neuropathic pain model; however, it is unknown whether these effects involve autophagy induction.

Methods:

We investigated the relationship between HRS and cell autophagy in a neuropathic pain model generated by chronic constriction injury (CCI) in Sprague-Dawley rats. Rats received an intraperitoneal injection of HRS (10 mL/kg daily, from 1 day before until 14 days after CCI), 3MA (autophagy inhibitor), 2ME2 (HIF-1α inhibitor), or EDHB (HIF-1α agonist). The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were tested 1 day before and 1, 3, 7, 10, and 14 days after the operation. HIF-1α and cell autophagy markers in the spinal cord were evaluated by western blotting and real-time PCR assays at 14 days after CCI. Autophagosomes with double membranes were identified by transmission electron microscopy.

Results:

CCI caused behavioral hypersensitivity to mechanical and thermal stimulation in the hind-paw of the injured side. HRS improved MWT and TWL, activated autophagy, and increased autophagosomes and autolysosomes in CCI rats. 3-MA aggravated hyperalgesia and allodynia and suppressed autophagy, while EDHB attenuated hyperalgesia and activated the autophagy procedure and the HIF-1α downstream target gene BNIP3. HIF-1α inhibitors reversed the regulatory effects of HRS on autophagy in CCI rats at 14 days after spinal cord injury.

Conclusion:

HRS reduced mechanical hyperalgesia and activation of cell autophagy in neuropathic pain through a HIF1-dependent pathway.

PMID:
29888265
PMCID:
PMC5985079
DOI:
10.1155/2018/4670834
[Indexed for MEDLINE]
Free PMC Article

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