Excess intracellular ATP causes neuropathic pain following spinal cord injury

Nobuhiko Nakajima, Yuichiro Ohnishi, Masamichi Yamamoto, Daiki Setoyama, Hirohiko Imai, Tomofumi Takenaka, Mari Matsumoto, Koichi Hosomi, Yoichi Saitoh, Hidemasa Furue, Haruhiko Kishima

研究成果: ジャーナルへの寄稿学術誌査読

抄録

Intractable neuropathic pain following spinal cord injury (NP-SCI) reduces a patient’s quality of life. Excessive release of ATP into the extracellular space evokes neuroinflammation via purinergic receptor. Neuroinflammation plays an important role in the initiation and maintenance of NP. However, little is known about whether or not extracellular ATP cause NP-SCI. We found in the present study that excess of intracellular ATP at the lesion site evokes at-level NP-SCI. No significant differences in the body weight, locomotor function, or motor behaviors were found in groups that were negative and positive for at-level allodynia. The intracellular ATP level at the lesion site was significantly higher in the allodynia-positive mice than in the allodynia-negative mice. A metabolome analysis revealed that there were no significant differences in the ATP production or degradation between allodynia-negative and allodynia-positive mice. Dorsal horn neurons in allodynia mice were found to be inactivated in the resting state, suggesting that decreased ATP consumption due to neural inactivity leads to a build-up of intracellular ATP. In contrast to the findings in the resting state, mechanical stimulation increased the neural activity of dorsal horn and extracellular ATP release at lesion site. The forced production of intracellular ATP at the lesion site in non-allodynia mice induced allodynia. The inhibition of P2X4 receptors in allodynia mice reduced allodynia. These results suggest that an excess buildup of intracellular ATP in the resting state causes at-level NP-SCI as a result of the extracellular release of ATP with mechanical stimulation.

本文言語英語
論文番号483
ジャーナルCellular and Molecular Life Sciences
79
9
DOI
出版ステータス出版済み - 9月 2022
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 分子医療
  • 分子生物学
  • 薬理学
  • 細胞および分子神経科学
  • 細胞生物学

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