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Sequestration of artemin reduces inflammation‐induced activation and sensitization of bone marrow nociceptors in a rodent model of carrageenan‐induced inflammatory bone pain
Author(s) -
Nencini Sara,
Thai Jenny,
Ivanusic Jason J.
Publication year - 2019
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1315
Subject(s) - nociceptor , sensitization , bone marrow , inflammation , medicine , stimulation , nociception , immunology , receptor
Background Pathologies that affect the bone marrow have a significant inflammatory component; however, it is not clear how inflammatory mediators affect nociceptive nerve terminals within the marrow cavity. Methods In this study, an in vivo bone‐nerve preparation was used to directly record the physiological response properties of bone marrow nociceptors innervating the tibial marrow cavity of rats, before and after application of the inflammatory agent carrageenan. In addition, endogenous artemin was sequestered by application of an artemin neutralizing antibody to determine if this could prevent the inflammation‐induced physiological changes observed. Results A single injection of carrageenan administered into the tibial marrow cavity produced rapid changes in weight bearing (pain‐like behaviour) in conscious animals. Carrageenan, but not saline, activated bone marrow nociceptors in whole‐nerve recordings and sensitized a subtype of Aδ‐bone marrow nociceptors to mechanical stimulation. The activation and sensitization had a rapid time course that matched that of pain‐like behaviours. Sequestration of endogenous artemin significantly reduced carrageenan‐induced increases in ongoing activity and completely abolished sensitization of bone marrow nociceptors to mechanical stimulation. Conclusions These observations indicate that inflammation affects the activity and sensitivity of bone marrow nociceptors; that artemin plays a role in these changes; and that artemin might be a promising target for pharmacological manipulations in the treatment of inflammatory bone pain. Significance Most pathologies that affect the bone marrow have an inflammatory component. We have used a model of carrageenan‐induced inflammation to show that sequestration of artemin reduces inflammation‐induced activation and sensitization of bone marrow nociceptors. Our findings suggest that artemin signalling is a target for the treatment of inflammatory bone pain.