Departments of Urology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, 60611, USA.
Division of Pediatric Gastroenterology, Children's Mercy Hospital, Kansas City, MO, USA.
Sci Rep. 2018 May 8;8(1):7188. doi: 10.1038/s41598-018-24056-0.
The etiology of chronic pelvic pain syndromes remains unknown. In a murine urinary tract infection (UTI) model, lipopolysaccharide of uropathogenic E. coli and its receptor TLR4 are required for post-UTI chronic pain development. However, downstream mechanisms of post-UTI chronic pelvic pain remain unclear. Because the TRPV1 and MCP-1/CCR2 pathways are implicated in chronic neuropathic pain, we explored their role in post-UTI chronic pain. Mice were infected with the E. coli strain SΦ874, known to produce chronic allodynia, and treated with the TRPV1 antagonist capsazepine. Mice treated with capsazepine at the time of SΦ874 infection failed to develop chronic allodynia, whereas capsazepine treatment of mice at two weeks following SΦ874 infection did not reduce chronic allodynia. TRPV1-deficient mice did not develop chronic allodynia either. Similar results were found using novelty-suppressed feeding (NSF) to assess depressive behavior associated with neuropathic pain. Imaging of reporter mice also revealed induction of MCP-1 and CCR2 expression in sacral dorsal root ganglia following SΦ874 infection. Treatment with a CCR2 receptor antagonist at two weeks post-infection reduced chronic allodynia. Taken together, these results suggest that TRPV1 has a role in the establishment of post-UTI chronic pain, and CCR2 has a role in maintenance of post-UTI chronic pain.
慢性盆腔疼痛综合征的病因尚不清楚。在小鼠尿路感染 (UTI) 模型中，尿路致病性大肠杆菌的脂多糖及其受体 TLR4 是 UTI 后慢性疼痛发展所必需的。然而，UTI 后慢性盆腔疼痛的下游机制仍不清楚。因为 TRPV1 和 MCP-1/CCR2 途径与慢性神经性疼痛有关，所以我们探讨了它们在 UTI 后慢性疼痛中的作用。将大肠杆菌菌株 SΦ874 感染小鼠，该菌株已知会产生慢性痛觉过敏，并给予 TRPV1 拮抗剂辣椒素治疗。在 SΦ874 感染时给予辣椒素治疗的小鼠未能发展为慢性痛觉过敏，而在 SΦ874 感染后两周给予辣椒素治疗的小鼠则不会减轻慢性痛觉过敏。TRPV1 缺陷型小鼠也没有发展为慢性痛觉过敏。使用新奇抑制进食 (NSF) 评估与神经性疼痛相关的抑郁行为也得到了类似的结果。报告小鼠的成像也显示，在 SΦ874 感染后，骶神经根节中 MCP-1 和 CCR2 的表达被诱导。在感染后两周给予 CCR2 受体拮抗剂治疗可减轻慢性痛觉过敏。总之，这些结果表明 TRPV1 在 UTI 后慢性疼痛的建立中起作用，而 CCR2 在 UTI 后慢性疼痛的维持中起作用。
