The spinal α7-nicotinic acetylcholine receptor contributes to the maintenance of cancer-induced bone pain

Yang, T, Zhou, Y, Zhang, W, Zhang, L, Chen, S, Chen, C, Gao, F, Yang, H, Manyande, Anne ORCID: https://orcid.org/0000-0002-8257-0722, Wang, J, Tian, Y and Tian, X (2021) The spinal α7-nicotinic acetylcholine receptor contributes to the maintenance of cancer-induced bone pain. Journal of Pain Research, 2021 (14). pp. 441-452.

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Abstract

Introduction: Cancer-induced bone pain (CIBP) is acknowledged as a multifactorial chronic pain that tortures advanced cancer patients, but existing treatment strategies for CIBP have not been satisfactory yet. Investigators have demonstrated that the activation of α 7-nAChRs exerts analgesic effects in some chronic pain models. However, the role of spinal α 7-nAChRs in CIBP remains unknown. This study was designed to investigate the role of α 7-nAChRs in a well-established CIBP model induced by Walker 256 rat mammary gland carcinoma cells.
Methods: The paw withdrawal threshold (PWT) of the ipsilateral hind paw was measured using von Frey filament. The expressions of spinal α 7-nAChRs and NF-κB were measured with Western blotting analysis. Immunofluorescence was employed to detect the expression of α 7-nAChRs and co-expressed of α 7-nAChRs with NeuN or GFAP or Iba1.
Results: Experiment results showed that the expression of spinal α 7-nAChRs was significantly downregulated over time in CIBP rats, and in both CIBP rats and sham rats, most of the α 7-nAChRs located in neurons. Behavioral data suggested PNU-282,987, a selective α 7-nAChRs agonist, dose-dependently produced analgesic effect and positive allosteric modulator could intensify its effects. Further, repeated administration of PNU-282,987 reversed the expression of α 7-nAChRs, inhibited the nuclear factor kappa B (NF-κB) signaling pathway, and attenuates CIBP-induced mechanical allodynia state as well.
Conclusion: These results suggest that the reduced expression of spinal α 7-nAChRs contributes to the maintenance of CIBP by upregulating NF-κB expression, which implying a novel pharmacological therapeutic target for the treatment of CIBP.

Keywords: cancer-induced bone pain, α 7-nAChR, NF-κB, PNU-282,987

Item Type: Article
Additional Information: This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.
Uncontrolled Keywords: cancer-induced bone pain, α 7-nAChR, NF-κB, PNU-282,987
Subjects: Medicine and health > Clinical medicine
Medicine and health
Related URLs:
Depositing User: Anne Manyande
Date Deposited: 16 Feb 2021 17:42
Last Modified: 22 Feb 2021 15:10
URI: http://repository.uwl.ac.uk/id/eprint/7675

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