Peripheral and central nervous system alterations in a rat model of inflammatory arthritis

被引:15
作者
Locke, Samantha [1 ,2 ]
Yousefpour, Noosha [1 ,2 ]
Mannarino, Matthew [1 ]
Xing, Shuran [1 ]
Yashmin, Fatima [1 ]
Bourassa, Valerie [1 ,2 ]
Ribeiro-da-Silva, Alfredo [1 ,2 ,3 ]
机构
[1] McGill Univ, Dept Pharmacol & Therapeut, 3655 Promenade Sir William Osler, Montreal, PQ H3G 1Y6, Canada
[2] McGill Univ, Alan Edwards Ctr Res Pain, Montreal, PQ, Canada
[3] McGill Univ, Dept Anat & Cell Biol, Montreal, PQ, Canada
关键词
Joint pain; Intra-articular CFA; Behaviour; Spinal cord; Disinhibition; Sprouting; Peptidergic afferents; Sympathetic; KCC2; Microglia; NGF; Western blot; Immunohistochemistry; GROWTH-FACTOR; RHEUMATOID-ARTHRITIS; SPINAL-CORD; IMMUNE CELLS; ANKLE JOINT; MOUSE MODEL; PAIN; NEURONS; MECHANISMS; ALLODYNIA;
D O I
10.1097/j.pain.0000000000001837
中图分类号
R614 [麻醉学];
学科分类号
100217 ;
摘要
It is consistently reported that in inflammatory arthritis (IA), pain may continue despite well-controlled inflammation, most likely due to interactions between joint pathology and pain pathway alterations. Nervous system alterations have been described, but much remains to be understood about neuronal and central non-neuronal changes in IA. Using a rat model of IA induced by intra-articular complete Freund's adjuvant injection, this study includes a thorough characterization of joint pathology and objectives to identify peripheral innervation changes and alterations in the spinal dorsal horn (DH) that could alter DH excitatory balancing. Male and female rats displayed long-lasting pain-related behavior, but, in agreement with our previous studies, other pathological alterations emerged only at later times. Cartilage vascularization, thinning, and decreased proteoglycan content were not detectable in the ipsilateral cartilage until 4 weeks after complete Freund's adjuvant. Sympathetic and peptidergic nociceptive fibers invaded the ipsilateral cartilage alongside blood vessels, complex innervation changes were observed in the surrounding skin, and ipsilateral nerve growth factor protein expression was increased. In the DH, we examined innervation by peptidergic and nonpeptidergic nociceptors, inhibitory terminal density, the KCl cotransporter KCC2, microgliosis, and astrocytosis. Here, we detected the presence of microgliosis and, interestingly, an apparent loss of inhibitory terminals and decreased expression of KCC2. In conclusion, we found evidence of anatomical, inflammatory, and neuronal alterations in the peripheral and central nervous systems in a model of IA. Together, these suggest that there may be a shift in the balance between incoming and outgoing excitation, and modulatory inhibitory tone in the DH.
引用
收藏
页码:1483 / 1496
页数:14
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