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The effects of hyperbaric oxygen therapy on neuropathic pain via mitophagy in microglia
1Department of Anesthesiology, Shengjing Hospital, China Medical University.
Purpose:
Hyperbaric oxygen (HBO) therapy has been suggested to palliate neuropathic pain, but the mechanisms involved are not well understood. This study explored the involvement of microglial mitophagy via HBO relative to neuropathic pain therapy.
Materials And Methods:
A total of 80 male Sprague Dawley rats were randomly divided into two groups: a normal group (n = 40) and a mitophagy inhibitor group (n = 40) in which the mitophagy inhibitor cyclosporin A (CsA) was administrated prior to chronic constriction injury (CCI). Groups (n = 10 rats per group) consisted of the following: control (C), sham operation (S), sciatic nerve with chronic constriction injury (CCI), and a CCI plus HBO treatment (CCI + HBO). Pain-related behaviors were evaluated using mechanical withdraw tendency and thermal withdraw latency analysis. Mitochondrial membrane potential was measured, and Western blot was employed to assess expression of NIX and BNIP3. Immunofluorescence changes in neuron protein (NESTIN) and mitochondria inner or outer layer proteins (TIM23, TOM20) were examined.
Results:
HBO significantly ameliorated pain-related behaviors, which were downregulated by mitophagy inhibitors (P < 0.05). Mitochondrial membrane potential indexes were decreased after HBO therapy, but were reversed in the mitophagy inhibitor group (P < 0.05). HBO upregulated NIX and BNIP3 expression, which did not occur in the CCI group (P < 0.05). However, expression was reduced when mitophagy inhibitors were administered. Immunofluorescence examination showed that mitophagy in microglia was induced by CCI, which was upregulated after HBO treatment. This phenomenon was not observed in the mitophagy inhibitor group.
Conclusions:
HBO therapy palliated CCI-induced neuropathic pain in rats by upregulating microglial mitophagy. These results could serve as guidelines to improve neuropathic pain therapy using HBO to maximize therapeutic efficiency.
Insights
Hyperbaric oxygen therapy effectively reduced neuropathic pain in rats by enhancing microglial mitophagy. This finding offers new strategies for improving pain management through targeted hyperbaric oxygen treatments.
Area of Science:
- Neuroscience
- Cell Biology
- Pain Management
Background:
- Neuropathic pain is a debilitating condition with complex underlying mechanisms.
- Hyperbaric oxygen (HBO) therapy is a potential treatment for neuropathic pain, but its precise mechanisms remain unclear.
Purpose of the Study:
- To investigate the role of microglial mitophagy in hyperbaric oxygen (HBO) therapy for neuropathic pain.
- To elucidate the molecular pathways involved in HBO's therapeutic effects on neuropathic pain.
Main Methods:
- Utilized a rat model of chronic constriction injury (CCI) to induce neuropathic pain.
- Administered HBO therapy and mitophagy inhibitors (cyclosporin A) to assess their effects on pain behaviors.
- Analyzed mitochondrial function, expression of mitophagy-related proteins (NIX, BNIP3), and microglial mitophagy via immunofluorescence.
Main Results:
- HBO therapy significantly alleviated neuropathic pain behaviors in rats.
- HBO treatment upregulated microglial mitophagy and the expression of NIX and BNIP3.
- Mitophagy inhibitors reversed the beneficial effects of HBO, confirming the role of mitophagy.
Conclusions:
- Hyperbaric oxygen therapy palliates neuropathic pain by enhancing microglial mitophagy.
- These findings provide a mechanistic basis for utilizing HBO in neuropathic pain management.
- Targeting microglial mitophagy could enhance the therapeutic efficacy of HBO for pain relief.
