Chronic pain is a major clinical problem with limited treatment options. Previous studies have demonstrated that activation of adenosine monophosphate-activated protein kinase (AMPK) can attenuate neuropathic pain. Inflammation/immune response at the site of complete Freund’s adjuvant (CFA) injection is known to be a critical trigger of the pathological changes that produce inflammatory pain. However, whether activation of AMPK produces an analgesic effect through inhibiting the proinflammatory cytokines, including interleukin-1β (IL-1β), in inflammatory pain remains unknown. Inflammatory pain was induced in mice injected with CFA. The effects of AICAR (5-aminoimidazole-4-carboxyamide ribonucleoside, an AMPK activator), Compound C (an AMPK inhibitor), and IL-1ra (an IL-1 receptor antagonist) were tested at day 4 after CFA injection. Inflammatory pain was assessed with von Frey filaments and hot plate. Immunoblotting, hematoxylin and eosin (H&E) staining, and immunofluorescence were used to assess inflammation-induced biochemical changes. The AMPK activator AICAR produced an analgesic effect and inhibited the level of proinflammatory cytokine IL-1β in the inflamed skin in mice. Moreover, activation of AMPK suppressed CFA-induced NF-κB p65 translocation from the cytosol to the nucleus in activated macrophages (CD68+ and CX3CR1+) of inflamed skin tissues. Subcutaneous injection of IL-1ra attenuated CFA-induced inflammatory pain. The AMPK inhibitor Compound C and AMPKα shRNA reversed the analgesic effect of AICAR and the effects of AICAR on IL-1β and NF-κB activation in inflamed skin tissues. Our study provides new information that AMPK activation produces the analgesic effect by inhibiting NF-κB activation and reducing the expression of IL-1β in inflammatory pain.

Background: Chemotherapy is an important treatment for children with cancer, and chemotherapy-induced pain is an important role in affecting patients' quality of life. In our study, bibliometric analysis was used to identify current research hotspots and future research trends of chemotherapy and pain in children over the last decade. Our findings can provide a reference for the research in the field of chemotherapy and pain in children.Method: Publications of chemotherapy and pain in children were collected from the Web of Science Core Collection database. CiteSpace was used to analyze publication characteristics from 2013 to 2022.Results: We identified 1,130 eligible publications in the field of chemotherapy and pain in children, with an increasing trend of publications over the last decade. In the field of chemotherapy and pain in children, the United States had the most publication with 346, followed by China with 135. The author with the most published papers was Pamela S Hinds (n = 8) from the United States. The journals that published the most papers were the Journal of pediatric hematology oncology (n = 44) and Medicine (n = 44). The Journal of Clinical Oncology was cited the most frequency (n = 422). St. Jude Children's Research Hospital had the most publication (n = 23). The specific keywords related to the field of chemotherapy and pain in children were “children”, “chemotherapy”, “management”, “childhood cancer”, “randomized controlled trial” and “efficacy”. Emerging research focuses predominantly on symptomatic and supportive interventions for chemotherapy and pain in children.Conclusion: Attention to chemotherapy and pain in children with cancer was insufficient. This bibliometric analysis showed the upward trend of chemotherapy and pain in children over the last decade. More studies are needed to improve the quality of life in children with chemotherapy-induced pain. This study may provide useful information to guide future research on chemotherapy and pain in children.