Excess intracellular ATP causes neuropathic pain following spinal cord injury.


Journal

Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402

Informations de publication

Date de publication:
16 Aug 2022
Historique:
received: 07 06 2022
accepted: 01 08 2022
revised: 16 07 2022
entrez: 16 8 2022
pubmed: 17 8 2022
medline: 19 8 2022
Statut: epublish

Résumé

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.

Identifiants

pubmed: 35972649
doi: 10.1007/s00018-022-04510-z
pii: 10.1007/s00018-022-04510-z
doi:

Substances chimiques

Adenosine Triphosphate 8L70Q75FXE

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

483

Subventions

Organisme : Japan Society for the Promotion of Science
ID : JP19K09527
Organisme : Japan Society for the Promotion of Science
ID : JP22K09248
Organisme : Japan Agency for Medical Research and Development
ID : JP20ek0610017

Informations de copyright

© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

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Auteurs

Nobuhiko Nakajima (N)

Department of Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

Yuichiro Ohnishi (Y)

Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan. ohnishinsurg@gmail.com.
Department of Neurosurgery, Osaka Gyoumeikan Hospital, Osaka, Japan. ohnishinsurg@gmail.com.

Masamichi Yamamoto (M)

Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan. yamamoto.mailserver@gmail.com.

Daiki Setoyama (D)

Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Hirohiko Imai (H)

Department of Systems Science, Graduate School of Informatics, Kyoto University, Kyoto, Japan.

Tomofumi Takenaka (T)

Department of Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

Mari Matsumoto (M)

Department of Research Promotion and Management, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shimmachi, Suita, Osaka, 564-8565, Japan.

Koichi Hosomi (K)

Department of Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Department of Neuromodulation and Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

Yoichi Saitoh (Y)

Department of Neuromodulation and Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

Hidemasa Furue (H)

Department of Neurophysiology, Hyogo College of Medicine, Hyogo, Japan.

Haruhiko Kishima (H)

Department of Neurosurgery, Graduate School of Medicine, Osaka University, Osaka, Japan.

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