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Updated: Apr 20, 2026
Modified Spared Nerve Injury Surgery Model of Neuropathic Pain in Mice
Published on: January 25, 2022
Inhaled hydrogen sulfide prevents neuropathic pain after peripheral nerve injury in mice
Kotaro Kida1, Eizo Marutani1, Rebecca K Nguyen1
1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Abstract:
Increasing evidence suggests that the pathogenesis of neuropathic pain is mediated through activation of microglia in the spinal cord. Hydrogen sulfide attenuates microglial activation and central nervous system inflammation; however, the role of hydrogen sulfide in neuropathic pain is unclear. In this study, we examined the effects of hydrogen sulfide breathing on neuropathic pain in mice. C57BL/6J mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. After CCI, mice breathed air alone or air mixed with hydrogen sulfide at 40 ppm for 8 h on 7 consecutive days. The expression levels of inflammatory cytokines including interleukin 6 (IL-6) were measured in the spinal cord. Effects of hydrogen sulfide on IL-6-induced activation of microglia were examined in primary rat microglia. Mice that breathed air alone exhibited the neuropathic pain behavior including mechanical allodynia and thermal hyperalgesia and increased mRNA levels of IL-6 and chemokine CC motif ligand 2 (CCL2) after CCI. Inhaled hydrogen sulfide prevented the neuropathic pain behavior and attenuated the upregulation of inflammatory cytokines. Sodium sulfide inhibited IL-6-induced activation of primary microglia. These results suggest that inhaled hydrogen sulfide prevents the development of neuropathic pain in mice possibly via inhibition of the activation of microglia in the spinal cord.
Insights
Inhaled hydrogen sulfide (H2S) can prevent neuropathic pain in mice by reducing spinal cord inflammation and microglia activation. This study shows H2S inhalation effectively treats pain behaviors and cytokine upregulation post-nerve injury.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Neuropathic pain pathogenesis involves spinal cord microglia activation.
- Hydrogen sulfide (H2S) is known to reduce central nervous system inflammation.
- The specific role of H2S in neuropathic pain remains unclear.
Purpose of the Study:
- To investigate the therapeutic potential of inhaled hydrogen sulfide in a mouse model of neuropathic pain.
- To determine the effects of H2S on microglial activation and inflammatory cytokine expression in the spinal cord.
Main Methods:
- Mice underwent chronic constriction injury (CCI) of the sciatic nerve.
- Post-CCI, mice inhaled either air or air mixed with 40 ppm H2S for 8 hours daily over 7 days.
- Spinal cord inflammatory cytokine levels (IL-6, CCL2) and neuropathic pain behaviors (mechanical allodynia, thermal hyperalgesia) were assessed. In vitro studies examined H2S effects on IL-6-induced primary microglia activation.
Main Results:
- CCI mice exposed to air alone developed significant neuropathic pain behaviors and elevated spinal cord IL-6 and CCL2 mRNA levels.
- Inhaled H2S treatment prevented the development of mechanical allodynia and thermal hyperalgesia.
- H2S inhalation attenuated the upregulation of inflammatory cytokines in the spinal cord and inhibited IL-6-induced microglia activation in vitro.
Conclusions:
- Inhaled hydrogen sulfide effectively prevents the development of neuropathic pain in mice following sciatic nerve injury.
- H2S likely exerts its protective effects by inhibiting spinal cord microglia activation and reducing neuroinflammation.
- These findings highlight H2S as a potential therapeutic agent for neuropathic pain management.
