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

Sagar, Devi Rani and Staniaszek, Lydia E. and Okine, Bright N. and Woodhams, Stephen and Norris, Leonie M. and Pearson, Richard G. and Garle, Michael J. and Alexander, Stephen P.H. and Bennett, Andrew J. and Barrett, David A. and Kendall, David A. and Scammell, Brigitte E. and Chapman, Victoria (2010) Tonic modulation of spinal hyperexcitability by the endocannabinoid receptor system in a rat model of osteoarthritis pain. Arthritis and Rheumatism, 62 (12). pp. 3666-3676. ISSN 0004-3591

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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.

Item Type: Article
Schools/Departments: University of Nottingham UK Campus > Faculty of Medicine and Health Sciences > School of Life Sciences > School of Biomedical Sciences
Depositing User: de Sousa, Mrs Shona
Date Deposited: 10 Apr 2014 09:58
Last Modified: 13 Sep 2016 16:03
URI: http://eprints.nottingham.ac.uk/id/eprint/2938

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