Aloyouny Ashwag Yagoub, Bepari Asmatanzeem, Rahman Ishrat
College of Dentistry, Princess Nourah bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia.
College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia.
J Pain Res. 2020 Aug 6;13:1987-2001. doi: 10.2147/JPR.S254276. eCollection 2020.
CXCR3 is a well-known receptor involved in immune cell recruitment and inflammation. Pathological inflammation leads to pain stimulation and hence nociception. Therefore, we decided to review the recent research on CXCR3 to identify its precise role in the modulation of pain in a variety of clinical conditions targeting various regions of the body. Studies were selected from PubMed Medline, which relate CXCR3 to the progression of diseases with either bone cancer pain, neuropathic pain, cystitis pain, osteoarthritis and rheumatoid arthritis pain, dental pain, in particular, periodontitis and pulpitis. In all the diseases studied, a high prevalence of CXCR3 and/or its ligand were identified where CXCR3 is a key player in the pathophysiological process of many inflammatory conditions. CXCR3 and its ligands, particularly CXCL10, modulate nociception via actions in the dorsal root ganglia and dorsal horn of the spinal cord, in cases of bone cancer pain, neuropathic, and joint pain. However, with the other studied disease, no direct link to pain has been made, although it contributes to the pathological progression of the diseases and hence would be a causal factor for the pain. Furthermore, CXCR3 appears to play a role in desensitizing the opioid receptor in the descending modulatory pathway within the brain stem as well as modulating opioid-induced hyperalgesia in the dorsal horn of the spinal cord. Further research is required for understanding the exact mechanisms of CXCR3 in pain modulation centrally and peripherally. A greater understanding of the immunological activities and pharmacological consequence of CXCR3 and its ligands could help in the discovery of newer drugs for modulating pain arising from pathogenic or inflammatory sources. Given the significance of the CXCR3 for nociception, its utilization may prove to be beneficial as a target for analgesia.
CXCR3是一种参与免疫细胞募集和炎症反应的知名受体。病理性炎症会导致疼痛刺激，进而引发伤害感受。因此，我们决定回顾关于CXCR3的最新研究，以确定其在针对身体各个部位的多种临床病症中疼痛调节的确切作用。研究是从PubMed Medline中选取的，这些研究将CXCR3与骨癌疼痛、神经性疼痛、膀胱炎疼痛、骨关节炎和类风湿性关节炎疼痛、牙科疼痛（特别是牙周炎和牙髓炎）等疾病的进展相关联。在所有研究的疾病中，均发现CXCR3和/或其配体的高患病率，其中CXCR3是许多炎症病症病理生理过程中的关键因素。在骨癌疼痛、神经性疼痛和关节疼痛的情况下，CXCR3及其配体，特别是CXCL10，通过在背根神经节和脊髓背角的作用来调节伤害感受。然而，对于其他研究的疾病，虽然它促成了疾病的病理进展，因此可能是疼痛的一个因果因素，但尚未建立与疼痛的直接联系。此外，CXCR3似乎在使脑干内下行调节通路中的阿片受体脱敏以及调节脊髓背角的阿片类药物诱导的痛觉过敏方面发挥作用。需要进一步研究以了解CXCR3在中枢和外周疼痛调节中的确切机制。对CXCR3及其配体的免疫活性和药理学后果有更深入的了解，可能有助于发现用于调节由致病或炎症源引起的疼痛的新型药物。鉴于CXCR3对伤害感受的重要性，将其作为镇痛靶点可能会被证明是有益的。
