Animal Pharmacology Research Group of Quebec (GREPAQ), Department of Veterinary Biomedicine, Faculty of Veterinary Medicine, Université de Montréal, St.-Hyacinthe, QC J2S 7C6, Canada; Osteoarthritis Research Unit, Université de Montréal Hospital Research Center (CRCHUM), Pavillon R, Montreal, QC H2X 0A9, Canada.
Osteoarthritis Research Unit, Université de Montréal Hospital Research Center (CRCHUM), Pavillon R, Montreal, QC H2X 0A9, Canada.
Neuropeptides. 2017 Oct;65:56-62. doi: 10.1016/j.npep.2017.04.009. Epub 2017 Apr 24.
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.
On day (D) 0, OA was induced by an IA injection of monosodium iodoacetate (MIA). Rats receiving 2mg 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 1mg MIA, IA 2mg 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 2mg 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 2mg 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 2mg MIA groups (P=0.01).
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.
描述在大鼠化学诱导性骨关节炎（OA）后，疼痛功能评估、脊髓神经肽和关节软骨病变的变化的时间演变。
在第 0 天（D），通过关节内注射单碘乙酸（MIA）诱导 OA。在 D3、D7、D14 和 D21 时，对接受 2mg MIA 的大鼠进行时间评估，以测定脊髓中 P 物质（SP）、降钙素基因相关肽（CGRP）、缓激肽（BK）和生长抑素（STT）的总浓度，并评估软骨病变的严重程度。在 D21 时，将这些结果与 IA 1mg MIA、IA 2mg MIA 联合 D7、D14 和 D21 时的关节内利多卡因穿刺注射、假手术（无菌生理盐水）和未处理组进行比较。使用 von Frey 触觉测痛计连续评估触觉过敏。采用非参数和混合模型进行统计分析。在 2mg MIA 组中，触觉过敏在 D3 时出现，并持续至 D21。在 D7 和 D14 时，IA 内注射利多卡因可拮抗其作用。与未处理组相比，[STT]、[BK]和[CGRP]在 D7 时达到最大值，并在 D21 时保持稳定。对于[SP]，其增加延迟至 D14 并在 D21 时保持不变。除 2mg MIA 组的[STT]更高（P=0.029）外，两种 MIA 剂量之间的神经肽水平无差异。神经肽 SP 和 BK 对利多卡因治疗有反应。仅在 2mg MIA 组中，软骨病变严重程度的增加有显著差异（P=0.01）。
在 MIA OA 疼痛模型中，神经肽调节出现较早，证实中枢神经系统是 OA 疼痛量化的一个有吸引力的靶点。神经肽释放与软骨病变严重程度和功能评估之间的关系很有前景，需要进一步验证。
