Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form
D-Scholarship @ Pitt Banner and Links to Homepage

Cannabinoid CB<inf>2</inf> receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint

Burston, JJ and Sagar, DR and Shao, P and Bai, M and King, E and Brailsford, L and Turner, JM and Hathway, GJ and Bennett, AJ and Walsh, DA and Kendall, DA and Lichtman, A and Chapman, V (2013) Cannabinoid CB<inf>2</inf> receptors regulate central sensitization and pain responses associated with osteoarthritis of the knee joint. PLoS ONE, 8 (11).

[img]
Preview
 PDF
Published Version
Available under License : See the attached license file.
Download (795kB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.
Download (1kB)

Abstract

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies. Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that spinal administration of JWH133 inhibited noxious-evoked responses of spinal neurones in the model of OA pain, but not in control rats, indicating a novel spinal role of this target. We further demonstrate dynamic changes in spinal CB2 receptor mRNA and protein expression in an OA pain model. The expression of CB2 receptor protein by both neurones and microglia in the spinal cord was significantly increased in the model of OA. Hallmarks of central sensitization, significant spinal astrogliosis and increases in activity of metalloproteases MMP-2 and MMP-9 in the spinal cord were evident in the model of OA pain. Systemic administration of JWH133 attenuated these markers of central sensitization, providing a neurobiological basis for analgesic effects of the CB2 receptor in this model of OA pain. Analysis of human spinal cord revealed a negative correlation between spinal cord CB2 receptor mRNA and macroscopic knee chondropathy. These data provide new clinically relevant evidence that joint damage and spinal CB2 receptor expression are correlated combined with converging pre-clinical evidence that activation of CB2 receptors inhibits central sensitization and its contribution to the manifestation of chronic OA pain. These findings suggest that targeting CB2 receptors may have therapeutic potential for treating OA pain. © 2013 Burston et al.

Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Burston, JJ
Sagar, DR
Shao, Ppis11@pitt.eduPIS11
Bai, Mmib63@pitt.eduMIB63
King, E
Brailsford, L
Turner, JM
Hathway, GJ
Bennett, AJ
Walsh, DA
Kendall, DA
Lichtman, A
Chapman, V
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorPrice, Theodore JohnUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 25 November 2013
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 8
Number: 11
DOI or Unique Handle: 10.1371/journal.pone.0080440
Schools and Programs: School of Medicine > Radiology
Refereed: Yes
Date Deposited: 30 Jan 2014 17:58
Last Modified: 22 Jun 2021 10:55
URI: http://d-scholarship.pitt.edu/id/eprint/20403

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

Actions (login required)

View Item View Item