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Yang Chen, Xiaoen Bian, Junnan Wang, Fang Yan, Jing Gao, Tao Sun Department of Pain Management, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, People’s Republic of ChinaCorrespondence: Tao Sun, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwu Road, Jinan, Shandong, 250021, People’s Republic of China, Email suntaosdph@163.comPurpose: Chronic inflammatory pain is usually treated with oral non-steroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs can cause some adverse events, and local preparation is an important alternative drug. Currently, small sample clinical studies show that loxoprofen sodium hydrogel patch (LX-P) has good analgesic and anti-inflammatory effects; however, there is a lack of real-world clinical research data.Patients and Methods: This study included 60 patients with chronic inflammatory pain. They were treated with LX-P without affecting their real-world treatment for two weeks.Results: After 2 weeks of continuous medication, 93.33% of the patients stated that the treatment was effective. Only 3.33% of the patients had a relapse after 4 weeks. Moreover, the swelling range and degree of swelling decreased markedly and the dysfunction of the pain site was markedly alleviated. The total satisfaction of patients after treatment reached 90.00%.Conclusion: In this real-world observational study, LX-P showed good efficacy and safety in patients with chronic inflammatory pain.Keywords: loxoprofen sodium hydrogel patch, real-world study, chronic inflammatory pain, non-steroidal anti-inflammatory drugs

Ling-Ling Xu,1– 4,* Yao Yan,1– 3,* Yu-Min Yuan,1– 3 Ying Li,1– 3 Jun Jiang,1– 3 Li-Cai Zhang1– 3 1Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical University, Xuzhou, People’s Republic of China; 3NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou, People’s Republic of China; 4Department of Anesthesiology, Nanjing Gaochun People’s Hospital, Nanjing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li-Cai Zhang, Email licaizhang001@163.comObjective: To assess the receptors of TRPV1 and GABAB1 receptors that were colocalized in cerebrospinal fluid contacting nucleus (CSF-contact nucleus) of chronic inflammatory pain (CIP) rats bringing inspiration for reducing chronic pain.Methods: A rat model of CIP was constructed by plantar injection of complete Freund’s adjuvant (CFA), and the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured 1, 3, 5, 7, 10, and 14 days after plantar injection. In the first part of the experiment, rats with CIP were divided into the immunofluorescence group and the coimmunoprecipitation (Co-IP) group (n = 6). Rats in the immunofluorescence group were injected with the retrograde tracer CB conjugated with Alexa Fluor 594 into the lateral ventricle two days before the injection of CFA into the plantar surface of the left paw. Three days later, rats that exhibited hyperalgesia were perfused, and their brains were extracted and used for double immunofluorescence staining of the CSF-contacting nucleus. Rats in the Co-IP group were anesthetized and dissected 3 days after CFA injection, and fresh brain segments containing the CSF-contacting nucleus were collected for Co-IP to assess the colocalization of TRPV1 and GABAB1 in the CSF-contacting nucleus (n = 6). In the second part of the experiment, SD rats were divided into the normal saline group (control group) and the CFA group. Fresh CSF-contacting nucleus-containing tissues were collected for Western blot analysis 3 days after plantar injection to observe the changes in TRPV1 and GABAB1 expression in the CSF-contacting nucleus.Results: TRPV1 and GABAB1 were co-expressed in the CSF-contacting nucleus in rats with CIP, and their expression was upregulated.Conclusion: TRPV1 and GABAB1 in the CSF-contacting nucleus are jointly involved in CIP in rats, and there is a direct or indirect link between TRPV1 and GABAB1.Keywords: cerebrospinal fluid-contacting nucleus, TRPV1 receptor, GABAB1 receptor, chronic inflammatory pain

Jian-hua He,1,* Ling Yu,2,* Zhi-yong Wang,1 Qiang Wang,3 Jun-Li Cao,4 Lian-bing Gu1 1Department of Anesthesiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Ultrasound, Affiliated Hospital of Integrate Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing,People’s Republic of China; 3Department of Anesthesiology, Nanjing Meishan Hospital, Nanjing, People’s Republic of China; 4Jiangsu Key Laboratory of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lian-bing GuDepartment of Anesthesiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Baiziting 42#, Nanjing, Jiangsu 210009, People’s Republic of ChinaTel/fax +86 25 8328 4765Email lbg6519@163.comPurpose: Chronic inflammatory pain is a common condition in the clinic, and the underlying mechanism is not being completely understood. Various studies have demonstrated that central and peripheral sensitization and synaptic plasticity could play crucial functions in chronic inflammatory pain. Moreover, families of monocarboxylate transporters (MCTs) are closely related to cellular metabolism and synaptic plasticity, and it is also reported that MCTs participate in chronic inflammatory pain. Nevertheless, there is a probability of the engaging role of MCT 1 is in chronic inflammatory pain, but its specific cellular level mechanism is yet to be investigated. In our study, we hypothesized that MCT 1 in the spinal dorsal horn plays an important part in chronic inflammatory pain.Methods: In experiment A, rats were gone through nociceptive behavioral testing at 1 d day before and 1 d, 3 d, and 7 d after completing complete Freund’s adjuvant (CFA) injection. The specimens collected for detecting MCT 1 by Western blotting. In experiment B, rats were randomly divided into four groups. Intrathecal injection of MCT 1 inhibitor and nociceptive behavioral tests were performed 1 d day before and 1 d, 3 d, 7 d, 14 d, and 21 d after CFA injection. MCT 1 and p-ERK levels in spinal dorsal horn were measured by Western blotting, and GFAP in spinal dorsal horn was detected by immunofluorescence.Results: The expression of MCT 1 in the spinal dorsal horn was increased during chronic inflammatory pain in rats. The intrathecal injection of an MCT 1 inhibitor evidently diminished the expression of MCT 1 and GFAP in the spinal dorsal horn, and the behavioral nociceptive responses were also attenuated. Meanwhile, the expression of p-ERK was also decreased by the intrathecal injection of an MCT 1 inhibitor.Conclusion: Our results indicate that MCT 1 very likely play a critical role in regulating chronic inflammatory pain and may influence the regulation of synaptic plasticity via ERK in the spinal dorsal horn of rats.Keywords: chronic inflammatory pain, monocarboxylate transporter 1, spinal dorsal horn, astrocyte, synaptic plasticity

Yuanyuan Wu,1 Xinmiao Yao,2 Yongliang Jiang,1 Xiaofen He,1 Xiaomei Shao,1 Junying Du,1 Zui Shen,1 Qiaoying He,1 Jianqiao Fang1 1Department of Neurobiology and Acupuncture Research, The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 2The Third Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang, China Abstract: Pain is considered a multidimensional conscious experience that includes a sensory component and a negative affective-motivational component. The negative affective-motivational component of pain is different from the sensory component and amplifies the pain experience. Nowadays, a significant number of preclinical research groups have focused their attention on the affective symptoms of pain. In the present study, we investigated the pain aversion and anxiety-like behavior of the complete Freund’s adjuvant (CFA)-induced chronic pain model. CFA rats experienced spontaneous pain during pain-paired conditioning (pain aversion) and spontaneous pain produces an affective response (anxiety-like behavior). Moreover, pain aversion was gradually attenuated, while the anxiety-like behavior increased in 4 weeks. Therefore, although the negative effect (including pain aversion and anxiety) is always associated with hyperalgesia, the manifestations of negative effect may follow different time courses, which may influence the progress of primary disease. The findings illustrate that targeted therapy should focus on a specific aspect in different stages of pain. Our study emphasizes the necessity of using multiple tests to study pain comorbidities. Keywords: pain, pain aversion, pain affection, anxiety-like behavior, chronic inflammatory pain, rat

Objective: To assess the receptors of TRPV1 and GABA B1 receptors that were colocalized in cerebrospinal fluid contacting nucleus (CSF-contact nucleus) of chronic inflammatory pain (CIP) rats bringing inspiration for reducing chronic pain., Methods: A rat model of CIP was constructed by plantar injection of complete Freund's adjuvant (CFA), and the paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured 1, 3, 5, 7, 10, and 14 days after plantar injection. In the first part of the experiment, rats with CIP were divided into the immunofluorescence group and the coimmunoprecipitation (Co-IP) group (n = 6). Rats in the immunofluorescence group were injected with the retrograde tracer CB conjugated with Alexa Fluor 594 into the lateral ventricle two days before the injection of CFA into the plantar surface of the left paw. Three days later, rats that exhibited hyperalgesia were perfused, and their brains were extracted and used for double immunofluorescence staining of the CSF-contacting nucleus. Rats in the Co-IP group were anesthetized and dissected 3 days after CFA injection, and fresh brain segments containing the CSF-contacting nucleus were collected for Co-IP to assess the colocalization of TRPV1 and GABA B1 in the CSF-contacting nucleus (n = 6). In the second part of the experiment, SD rats were divided into the normal saline group (control group) and the CFA group. Fresh CSF-contacting nucleus-containing tissues were collected for Western blot analysis 3 days after plantar injection to observe the changes in TRPV1 and GABA B1 expression in the CSF-contacting nucleus., Results: TRPV1 and GABA B1 were co-expressed in the CSF-contacting nucleus in rats with CIP, and their expression was upregulated., Conclusion: TRPV1 and GABA B1 in the CSF-contacting nucleus are jointly involved in CIP in rats, and there is a direct or indirect link between TRPV1 and GABA B1 ., Competing Interests: The authors declare no potential conflicts of interest in this research., (© 2022 Xu et al.)