The peripheral and central expression of CGRP and IB4 in chronic pain from MIA-induced TMJOA rats

Abstract Background Chronic pain is the prevalent symptom that drives temporomandibular joint osteoarthritis (TMJOA) patients to ask for medical care, yet present alleviator remain less effective. This study aimed to investigate the actual TMJOA related chronic pain and the peripheral and central response in a TMJOA animal model. Methods This study firstly determined appropriate MIA dose based on pain behavior assessment with automated electronic von frey in rats. TMJOA pain correlated condylar structure alteration was evaluated by histological staining and Micro-CT. Then, the period of TMJOA chronic pain was further explored by assessing the alteration of glial fibrillary acidic protein (GFAP) positive astrocytes and ionized calcium binding adaptor molecule 1 (Iba1) positive microglia numbers in trigeminal spinal nucleus (TSN) and carrying out non-steroidal anti-inflammatory drugs (NSAIDS) pharmacological efficacy experiment. Finally, expression of neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP), isolectin B4 (IB4) in trigeminal ganglion (TG) and TSN was detected by immunofluorescence. Results 1 mg/50 µl of MIA was considered as an appropriate dose. MIA induced gradual alteration of condylar structure correlated to TMJ mechanical allodynia. GFAP and IBA-1 positive cell numbers upregulated on 2, 3, 4 weeks after MIA injection. NSAIDS pharmacological efficacy disappeared on 10 days post MIA injection. Up-regulation of CGRP and IB4 was found in TG and TSN on 2 and 4 weeks, while expression of NF200 remained unchanged. Conclusion MIA induced TMJOA related chronic pain period emerges on 2 weeks after MIA injection. CGRP, IB4 positive afferent in both peripheral and central nervous system may involve in TMJOA related chronic pain in rats.