Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain

Sagar, Devi Rani; Staniaszek, Lydia E.; Okine, Bright N.; Woodhams, Stephen; Norris, Leonie M.; Pearson, Richard G.; Garle, Michael J.; Alexander, Stephen P.H.; Bennett, Andrew J.; Barrett, David A.; Kendall, David A.; Scammell, Brigitte E.; Chapman, Victoria

Abstract

Objective. To investigate the impact of an experimental
model of osteoarthritis (OA) on spinal nociceptive
processing and the role of the inhibitory endocannabinoid
system in regulating sensory processing at the
spinal level.
Methods. Experimental OA was induced in rats
by intraarticular injection of sodium mono-iodoacetate
(MIA), and the development of pain behavior was
assessed. Extracellular single-unit recordings of wide
dynamic range (WDR) neurons in the dorsal horn were
obtained in MIA-treated rats and saline-treated rats.
The levels of endocannabinoids and the protein and
messenger RNA levels of the main synthetic enzymes for
the endocannabinoids (N-acyl phosphatidylethanolamine
phospholipase D [NAPE-PLD] and diacylglycerol
lipase [DAGL]) in the spinal cord were measured.
Results. Low-weight (10 gm) mechanically evoked
responses of WDR neurons were significantly (P < 0.05)
facilitated 28 days after MIA injection compared with
the responses in saline-treated rats, and spinal cord
levels of anandamide and 2-arachidonoyl glycerol
(2-AG) were increased in MIA-treated rats. Protein
levels of NAPE-PLD and DAGL, which synthesize
anandamide and 2-AG, respectively, were elevated in the
spinal cords of MIA-treated rats. The functional role of
endocannabinoids in the spinal cords of MIA-treated
rats was increased via activation of cannabinoid 1 (CB1)
and CB2 receptors, and blockade of the catabolism of
anandamide had significantly greater inhibitory effects
in MIA-treated rats compared with control rats.
Conclusion. Our findings provide new evidence
for altered spinal nociceptive processing indicative of
central sensitization and for adaptive changes in the
spinal cord endocannabinoid system in an experimental
model of OA. The novel control of spinal cord neuronal
responses by spinal cord CB2 receptors suggests that
this receptor system may be an important target for the
modulation of pain in OA.

Citation

Sagar, D. R., Staniaszek, L. E., Okine, B. N., Woodhams, S., Norris, L. M., Pearson, R. G., …Chapman, V. (2010). Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis and Rheumatism, 62(12), https://doi.org/10.1002/art.27698

• Journal Article Type: Article
• Publication Date: Dec 1, 2010
• Deposit Date: Apr 10, 2014
• Publicly Available Date: Apr 10, 2014
• Journal: Arthritis and Rheumatism
• Print ISSN: 0004-3591
• Electronic ISSN: 0004-3591
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 62
• Issue: 12
• DOI: https://doi.org/10.1002/art.27698
• Public URL: https://nottingham-repository.worktribe.com/output/1011623
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/art.27698/abstract