Published in:
BioMed Research International, 2018 (2018), Seite 1-13
Language:
English
DOI:
10.1155/2018/4670834
ISSN:
2314-6133;
2314-6141
Origination:
Footnote:
Description:
<jats:p><jats:italic>Background</jats:italic>. 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.<jats:italic> Methods</jats:italic>. 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-1<jats:italic>α</jats:italic> inhibitor), or EDHB (HIF-1<jats:italic>α</jats:italic> 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-1<jats:italic>α</jats:italic> 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.<jats:italic> Results</jats:italic>. 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-1<jats:italic>α</jats:italic> downstream target gene BNIP3. HIF-1<jats:italic>α</jats:italic> inhibitors reversed the regulatory effects of HRS on autophagy in CCI rats at 14 days after spinal cord injury.<jats:italic> Conclusion</jats:italic>. HRS reduced mechanical hyperalgesia and activation of cell autophagy in neuropathic pain through a HIF1-dependent pathway.</jats:p>