H2Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain


Neuropathic pain (NP) is characterized by persistent pain, tactile allodynia, or hyperalgesia. Peripheral nerve injury contributes to rapid progress of inflammatory response and simultaneously generates neuropathic pain. Hydrogen (H2) has anti-inflammation, anti-apoptosis, and anti-oxidative stress effects. Therefore, we hypothesized that H2 treatment could alleviate allodynic and hyperalgesic behaviors and the release of inflammatory factors in rats with neuropathic pain. Peripheral neuropathic pain was established by chronic constriction injury of sciatic nerve in rats. H2 was given twice through intraperitoneal injection at a daily dose of 10 mL/kg during days 1–7 after the operation. Hyperalgesia and allodynia were tested, pro-inflammatory factors of dorsal root ganglia (DRG) and the spinal cord were measured by enzyme-linked immunosorbent assay (ELISA) during days 1–14 after the operation, and heme oxygenase (HO)-1 messenger RNA (mRNA) and protein expression and activities were measured at day 14 after sciatic nerve injury in rats. After Sn (IV) protoporphyrin IX dihydrochloride (SnPP)-IX, hemin, and carbon monoxide-releasing molecule (CORM)-2 had been given for chronic constriction injury (CCI) in rats, the above indicators were assessed. We found that H2 clearly inhibited hyperalgesia and allodynia in neuropathic pain and also attenuated the pro-inflammatory cytokines TNF-α, IL-1β, and high-mobility group box (HMGB) 1. H2 improved HO-1 mRNA and protein expression and activities in the process of pain. SnPP-IX reversed the inhibitory effect of H2 on hyperalgesia and allodynia and on pro-inflammatory cytokines in DRG and the spinal cord. The antinociceptive and anti-inflammatory effects of H2 were involved in the activation of HO-1/CO signaling during neuropathic pain in rats.

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This work was supported by the National Natural Science Foundation of China (Nos. 81372033 to Yonghao Yu; 81101409 and 81471842 to KeliangXie) and the Natural Science Foundation of the Tianjin Science Committee (Nos. 13JCQNJC11400 to KeliangXie).

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The authors declare that they have no competing interests.

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Correspondence to Yonghao Yu.

Additional information

Yajun Chen, Hongguang Chen and Keliang Xie contributed equally to this work.


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Chen, Y., Chen, H., Xie, K. et al. H2Treatment Attenuated Pain Behavior and Cytokine Release Through the HO-1/CO Pathway in a Rat Model of Neuropathic Pain. Inflammation 38, 1835–1846 (2015). https://doi.org/10.1007/s10753-015-0161-x

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  • neuropathic pain
  • inflammation
  • cytokines
  • H2
  • HO-1
  • CO