Neonatal complete Freund's adjuvant-induced inflammation does not induce or alter hyperalgesic priming or alter adult distributions of C-fibre dorsal horn innervation

Cooper, Andrew H.; Hanmer, Jenna M.; Chapman, Victoria; Hathway, Gareth J.

Abstract

Introduction: Inflammation during the neonatal period can exacerbate pain severity following reinjury in adulthood. This is driven by alterations in the postnatal development of spinal and supraspinal nociceptive circuitry. However, the contribution of alterations in peripheral nociceptor function remains underexplored. Objectives: We examined whether neonatal complete Freund's adjuvant (CFA)-induced inflammation induced or altered adult development of hyperalgesic priming (inflammation-induced plasticity in nonpeptidergic C fibres) or altered postnatal reorganization of calcitonin gene-related peptide (CGRP)-expressing and isolectin B4 (IB4)-binding C fibres in the spinal dorsal horn (DH). Methods: After intraplantar injection of CFA at postnatal day (P) 1, we assessed mechanical thresholds in adult (P60) rats before and after intraplantar carrageenan. One week later, intraplantar PGE2-induced hypersensitivity persisting for 4 hours was deemed indicative of hyperalgesic priming. CGRP expression and IB4 binding were examined in adult rat DH after CFA. Results: P1 CFA did not alter baseline adult mechanical thresholds, nor did it change the extent or duration of carrageenan-induced hypersensitivity. However, this was slower to resolve in female than in male rats. Rats that previously received carrageenan but not saline were primed, but P1 hind paw CFA did not induce or alter hyperalgesic priming responses to PGE2. In addition, CFA on P1 or P10 did not alter intensity or patterns of CGRP or IB4 staining in the adult DH. Conclusion: Complete Freund's adjuvant-induced inflammation during a critical period of vulnerability to injury during early postnatal development does not induce or exacerbate hyperalgesic priming or alter the broad distribution of CGRP-expressing or IB4-binding afferent terminals in the adult dorsal horn.

Citation

Cooper, A. H., Hanmer, J. M., Chapman, V., & Hathway, G. J. (2020). Neonatal complete Freund's adjuvant-induced inflammation does not induce or alter hyperalgesic priming or alter adult distributions of C-fibre dorsal horn innervation. PAIN Reports, 5(6), Article e872. https://doi.org/10.1097/PR9.0000000000000872

• Journal Article Type: Article
• Acceptance Date: Oct 7, 2020
• Online Publication Date: Nov 30, 2020
• Publication Date: Nov 1, 2020
• Deposit Date: Oct 13, 2020
• Publicly Available Date: Nov 1, 2020
• Journal: Pain Reports
• Electronic ISSN: 2471-2531
• Publisher: Lippincott, Williams & Wilkins
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 6
• Article Number: e872
• DOI: https://doi.org/10.1097/PR9.0000000000000872
• Public URL: https://nottingham-repository.worktribe.com/output/4961846
• Publisher URL: https://journals.lww.com/painrpts/Fulltext/2020/12000/Neonatal_complete_Freund_s_adjuvant_induced.12.aspx