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IntroductionIt is well known that there are significant differences in the prevalence of chronic pain between males and females. Human and animal imaging studies have shown that chronic pain profoundly alters the structure and function of brain regions. However, there is limited research on the sex-specific mechanisms underlying the brain plasticity and adaptive changes associated with chronic pain. In this article, we conducted a multimodal study to evaluate how nerve injury-induced chronic pain affects the brain.MethodsMale and female Sprague-Dawley (SD) rats with spared nerve injury (SNI) model underwent resting-state functional magnetic resonance imaging (rs-fMRI) (male sham group: n = 18; male SNI group: n = 18; female sham group: n = 20; female SNI group: n = 18) and magnetic resonance diffusion tensor imaging (DTI) (male sham group: n = 23; male SNI group: n = 21; female sham group: n = 20; female SNI group: n = 21) scanning. ICA method, Fractional amplitude of low-frequency fluctuations (fALFF), immunofluorescence staining, and graph theory analysis was utilized to extract the rs-fMRI changes of brain regions of each group.ResultsUsing SNI model, which promotes long-lasting mechanical allodynia, we found that neuropathic pain deeply modified the intrinsic organization of the brain functional network in male and female rats (main effect of operation: F = 298.449, P < 0.001). 64 independent components (ICs) in the brain were divided and assigned to 16 systems. In male rats, we observed significant alterations in the microstructure of the hippocampal cornu ammonis 1 and cornu ammonis 2 (CA1/CA2) region, as indicated by increased mean diffusivity (MD) (CA1_L: P = 0.02; CA1_R: P = 0.031; CA2_L: P = 0.035; CA2_R: P = 0.015) and radial diffusivity (RD) (CA1_L: P = 0.028; CA1_R: P = 0.033; CA2_L: P = 0.037; CA2_R: P = 0.038) values, along with enhanced activating transcription factor 3 (ATF3) expression. Conversely, in female rats, we found significant increases in the fractional amplitude of low frequency fluctuations (fALFF) value within the hippocampal dentate gyrus (DG) (F = 5.419, P = 0.023), accompanied by elevated c-Fos signal (F = 6.269, P = 0.031). Furthermore, graph theory analysis revealed notable differences in the small-world network of the hippocampal system in female rats, characterized by reduced small-world attributes and increased inter-nodal transmission efficiency.DiscussionOur study indicates sex differences in structural and functional alterations in the hippocampal system in rats under chronic pain conditions. The results suggest that the hippocampus system plays an important role in the different mechanisms of chronic pain in different sexes. These findings provide reliable insights to explore the complex mechanisms underlying sex differences in chronic pain.

The disorder of mitochondrial functions plays a key role in oncogenesis. It is known that TSPO (18-kDa translocator protein) lies in a peculiar location at the interface between the mitochondria and the cytosol. TSPO is found in many types of tissues and is associated with multiple cellular processes, including apoptosis, cell proliferation and the regulation of mitochondria. However, the involvement of TSPO in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that TSPO is upregulated in HCC tissue and is associated with poor differentiation and poor survival. Multivariate analyses showed that TSPO was an independent predictive factor for poor prognosis in HCC patients. For the first time, we provided evidence that TSPO knockdown suppressed HCC cell proliferation in vitro. Hence, TSPO knockdown-induced apoptosis by disturbing mitochondrial function by enhancing the formation of reactive oxygen species (ROS) and decreasing the mitochondrial membrane potential (ΔΨm). An assay exploring the underlying mechanism revealed that TSPO knockdown modulated apoptotic regulatory proteins by regulating the ERK signaling pathway. Through a functional assay and an in vivo mouse model, the anti-cancer effect of PK11195, a specific ligand of TSPO, on HCC was revealed. In summary, TSPO may potentially serve as a prognostic biomarker, and TSPO might be a potential therapeutic target for HCC.

Objective: To explore the suitable dosage of dexmedetomidine preemptive analgesia combined with transverse abdominal muscle block for postoperative analgesia of colon cancer. Methods: From March 2018 to October 2019, 120 patients undergoing laparoscopic radical resection of colon cancer in our hospital were randomly divided into control group (group C, without dexmedetomidine), low-dose group (group L, 0.5 μg/kg), medium-dose group (group M, 1 μg/kg) and high-dose group (group M, 0.5μ g/kg) The Mean arterial pressure, MAP), Heart rate, HR) and visual analog scale (vas) pain were compared at 2 h(T0), 4 h(T1), 8 h(T2), 12 h(T3), 24 h(T4) and 48 h(T5) after operation The pain sensitive area of mechanical stimulation was measured at T4, T5 and 72 h (T6) after operation. The adverse reactions of patients after operation were compared. Results: Compared with C group, MAP and HR of L, M and H groups decreased in different degrees at each time point. MAP and HR of m and h groups were lower than those of l group at different time points (P<0.05). The VAS score and pain sensitive area of T4-T6 in l, m and h groups were significantly lower than those in c group (P<0.05), but there was no significant difference in Ramsay score among groups (p > 0.05). The vas score and pain sensitive area of m and h groups were lower than those of l group (P<0.05). Incidence of postoperative adverse reactions in l, m and h groups was lower than that in c group (P<0.05). Conclusion: Dexmedetomidine at doses of 1 μg/kg and 1.5 μg/kg has a good analgesic effect without increasing the incidence of adverse reactions. It is recommended that 1 μg/kg Dexmedetomidine be used as an auxiliary drug dose of ropivacaine during TAP block. At the same time, it is necessary to strengthen monitoring to avoid adverse reactions such as hypotension and bradycardia. [ABSTRACT FROM AUTHOR]