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Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain.
Eur J Pain. 2014 Mar; 18(3):326-37.EJ

Abstract

BACKGROUND

Treating bone cancer pain continues to be a major clinical challenge, and the underlying mechanisms of bone cancer pain remain elusive. Protease-activated receptor 2 (PAR2) has been reported to be involved in neurogenic inflammation, nociceptive pain and hyperalgesia. Here, we investigated the role of PAR2 in bone cancer pain development.

METHORDS

Expression of PAR2, mechanical allodynia, thermal hyperalgesia and neurochemical alterations induced by bone cancer pain were analysed in male, adult C3H/HeJ mice with tumour cell implantation (TCI). To investigate the contribution of PAR2 to bone cancer pain, PAR2 antagonist peptide and PAR2 knockout mice were used.

RESULTS

TCI produced bone cancer-related pain behaviours. Production and persistence of these pain behaviours were well correlated with TCI-induced up-regulation of PAR2 in sciatic nerve and dorsal root ganglia (DRG). PAR2 knockout and spinal administration of PAR2 antagonist peptide prevented and/or reversed bone cancer-related pain behaviours and associated neurochemical changes in DRG and dorsal horn (DH). TCI also induced proteases release in tumour-bearing tibia, sciatic nerve and DRG. Plantar injection of supernatant from sarcoma cells induced PAR2 up-regulation and intracellular calcium [Ca(2+) ]i increase in DRG, and calcitonin gene-related peptide accumulation in DH, as well as significant thermal and mechanical hyperalgesia, which were all in PAR2-dependent manners.

CONCLUSION

These findings suggest that PAR2 may be a key mediator for peripheral sensitization of bone cancer pain. Inhibiting PAR2 activation, especially during the early phase, may be a new therapy for preventing/suppressing development of bone cancer pain.

Authors+Show Affiliations

Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical College, China; Department of Neurobiology, Parker University, Dallas, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23893658

Citation

Liu, S, et al. "Protease-activated Receptor 2 in Dorsal Root Ganglion Contributes to Peripheral Sensitization of Bone Cancer Pain." European Journal of Pain (London, England), vol. 18, no. 3, 2014, pp. 326-37.
Liu S, Liu YP, Yue DM, et al. Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain. Eur J Pain. 2014;18(3):326-37.
Liu, S., Liu, Y. P., Yue, D. M., & Liu, G. J. (2014). Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain. European Journal of Pain (London, England), 18(3), 326-37. https://doi.org/10.1002/j.1532-2149.2013.00372.x
Liu S, et al. Protease-activated Receptor 2 in Dorsal Root Ganglion Contributes to Peripheral Sensitization of Bone Cancer Pain. Eur J Pain. 2014;18(3):326-37. PubMed PMID: 23893658.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protease-activated receptor 2 in dorsal root ganglion contributes to peripheral sensitization of bone cancer pain. AU - Liu,S, AU - Liu,Y-P, AU - Yue,D-M, AU - Liu,G-J, Y1 - 2013/07/28/ PY - 2013/06/26/accepted PY - 2013/7/30/entrez PY - 2013/7/31/pubmed PY - 2015/10/17/medline SP - 326 EP - 37 JF - European journal of pain (London, England) JO - Eur J Pain VL - 18 IS - 3 N2 - BACKGROUND: Treating bone cancer pain continues to be a major clinical challenge, and the underlying mechanisms of bone cancer pain remain elusive. Protease-activated receptor 2 (PAR2) has been reported to be involved in neurogenic inflammation, nociceptive pain and hyperalgesia. Here, we investigated the role of PAR2 in bone cancer pain development. METHORDS: Expression of PAR2, mechanical allodynia, thermal hyperalgesia and neurochemical alterations induced by bone cancer pain were analysed in male, adult C3H/HeJ mice with tumour cell implantation (TCI). To investigate the contribution of PAR2 to bone cancer pain, PAR2 antagonist peptide and PAR2 knockout mice were used. RESULTS: TCI produced bone cancer-related pain behaviours. Production and persistence of these pain behaviours were well correlated with TCI-induced up-regulation of PAR2 in sciatic nerve and dorsal root ganglia (DRG). PAR2 knockout and spinal administration of PAR2 antagonist peptide prevented and/or reversed bone cancer-related pain behaviours and associated neurochemical changes in DRG and dorsal horn (DH). TCI also induced proteases release in tumour-bearing tibia, sciatic nerve and DRG. Plantar injection of supernatant from sarcoma cells induced PAR2 up-regulation and intracellular calcium [Ca(2+) ]i increase in DRG, and calcitonin gene-related peptide accumulation in DH, as well as significant thermal and mechanical hyperalgesia, which were all in PAR2-dependent manners. CONCLUSION: These findings suggest that PAR2 may be a key mediator for peripheral sensitization of bone cancer pain. Inhibiting PAR2 activation, especially during the early phase, may be a new therapy for preventing/suppressing development of bone cancer pain. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/23893658/Protease_activated_receptor_2_in_dorsal_root_ganglion_contributes_to_peripheral_sensitization_of_bone_cancer_pain_ L2 - https://doi.org/10.1002/j.1532-2149.2013.00372.x DB - PRIME DP - Unbound Medicine ER -