Spinal neuropeptide modulation, functional assessment and cartilage lesions in a monosodium iodoacetate rat model of osteoarthritis. (October 2017)

• Record Type: Journal Article
• Authors: Otis, Colombe; Guillot, Martin; Moreau, Maxim; Martel-Pelletier, Johanne; Pelletier, Jean-Pierre; Beaudry, Francis; Troncy, Eric
• Is Part Of: Neuropeptides. Volume 65(2017)
• Page Start: 56
• Page End: 62
• Publication Date: 2017-10
• Subjects: OA osteoarthritis -- D day -- IA intra-articular -- MIA monosodium iodoacetate -- SP substance P -- CGRP calcitonin gene related-peptide -- BK bradykinin -- STT somatostatin -- (NF)-κB nuclear factor-kappa B -- L lidocaine -- PWT paw withdrawal threshold -- n number of animals -- w/v weight/volume -- v/v volume/volume -- p probability -- adj-P adjusted P value -- RR relative ratio -- w/v weight/volume -- SD standard deviation -- SEM standard error of the mean -- ATF-3 activating transcription factor-3; Neuropeptidomics -- Osteoarthritis -- Animal preclinical model -- Pain -- Nociception; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2017.04.009
• Languages: English
• ISSNs: 0143-4179

Abstract

Abstract: Background and aims: Characterising the temporal evolution of changes observed in pain functional assessment, spinal neuropeptides and cartilage lesions of the joint after chemical osteoarthritis (OA) induction in rats. Methods and results: On day (D) 0, OA was induced by an IA injection of monosodium iodoacetate (MIA). Rats receiving 2 mg MIA were temporally assessed at D3, D7, D14 and D21 for the total spinal cord concentration of substance P (SP), calcitonin gene related-peptide (CGRP), bradykinin (BK) and somatostatin (STT), and for severity of cartilage lesions. At D21, the same outcomes were compared with the IA 1 mg MIA, IA 2 mg MIA associated with punctual IA injection of lidocaine at D7, D14 and D21, sham (sterile saline) and naïve groups. Tactile allodynia was sequentially assessed using a von Frey anaesthesiometer. Non-parametric and mixed models were applied for statistical analysis. Tactile allodynia developed in the 2 mg MIA group as soon as D3 and was maintained up to D21. Punctual IA treatment with lidocaine counteracted it at D7 and D14. Compared to naïve, [STT], [BK] and [CGRP] reached a maximum as early as D7, which plateaued up to D21. For [SP], the increase was delayed up to D14 and maintained at D21. No difference in levels of neuropeptides was observed between MIA doses, except for higher [STT] in the 2 mg MIA group ( P = 0.029). Neuropeptides SP and BK were responsive to lidocaine treatment. The increase in severity of cartilage lesions was significant only in the 2 mg MIA groups ( P = 0.01). Conclusion: In the MIA OA pain model, neuropeptide modulation appears early, and confirms the central nervous system to be an attractive target for OA pain quantification. The relationship of neuropeptide release with severity of cartilage lesions and functional assessment are promising and need further validation. Highlights: Neuropeptides modulation appears early in the MIA OA pain model. Structural cartilaginous damages are related with somatostatin neuropeptide change. Central nervous system is the major target in OA pain quantification. The four neuropeptides spinal up-regulation supports central sensitisation.