Increasing evidence suggests that long-term opioids and pain induce similar adaptive changes in the brain's reward circuits, however, how pain alters the addictive properties of opioids remains poorly understood. In this study using a rat model of morphine self-administration (MSA), we found that short-term pain, induced by an intraplantar injection of complete Freund's adjuvant (CFA), acutely decreased voluntary morphine intake, but not food intake, only at a morphine dose that did not affect pain itself. Pre-treatment with indomethacin, a non-opioid inhibitor of pain, before the pain induction blocked the decrease in morphine intake. In rats with steady MSA, the protein level of GluA1 subunits of glutamate AMPA receptors (AMPARs) was significantly increased, but that of GluA2 was decreased, resulting in an increased GluA1/GluA2 ratio in central nucleus of the amygdala (CeA). In contrast, pain decreased the GluA1/GluA2 ratio in the CeA of rats with MSA. Microinjection of NASPM, a selective inhibitor of homomeric GluA1-AMPARs, into CeA inhibited morphine intake. Furthermore, viral overexpression of GluA1 protein in CeA maintained morphine intake at a higher level than controls and reversed the pain-induced reduction in morphine intake. These findings suggest that CeA GluA1 promotes opioid use and its upregulation is sufficient to increase opioid consumption, which counteracts the acute inhibitory effect of pain on opioid intake. These results demonstrate that the CeA GluA1 is a shared target of opioid and pain in regulation of opioid use, which may aid in future development of therapeutic applications in opioid abuse.

Kawasaki disease (KD) is an acute vasculitis, which leads to 20% of sufferers developing coronary artery aneurysm in children if not appropriately treated. Therefore, the early diagnosis of KD is essential for alleviating the risk of developing heart disease. MicroRNAs (miRNAs) are a large class of small non-coding RNAs which post-transcriptionally regulate gene expression and have been shown to play critical roles in numerous biological processes and diseases. In this study, we used high-throughput miRNA sequencing and found dozens of miRNAs are highly expressed in platelets. By comparing the miRNA expression profile of platelets of acute KD patients and other febrile patients, miR-222-3p is validated to be significantly upregulated in platelets of acute KD patients. Furthermore, KEGG pathway analysis shows that targets of miR-222-3p are enriched in immune-related signaling pathways. Our study uncovers the potential of miR-222-3p in platelets as biomarker for early diagnosis of Kawasaki disease.

Exposure to opiates induces locomotor sensitization in rodents, which has been proposed to correspond to the compulsive drug-seeking behaviour. Numerous studies have demonstrated that locomotor sensitization can occur in a dopamine transmission-independent manner; however, the underlying mechanisms are unclear.

The rostral ventromedial medulla (RVM) is a key brainstem structure that conveys powerful descending influence of the central pain-modulating system on spinal pain transmission and processing. Serotonergic (5-HT) neurons are a major component in the heterogeneous populations of RVM neurons and in the descending pathways from RVM. However, the descending influence of RVM 5-HT neurons on pain behaviors remains unclear.

This study was designed to explore differences in the ultrasonographic characteristics of medullary thyroid carcinoma (MTC) and papillary thyroid carcinoma (PTC). This study included 35 cases of MTC and 96 cases of PTC that were surgically and pathologically confirmed. Preoperative ultrasound images were retrospectively reviewed by two physicians (with 5 years' experience in thyroid ultrasound) under the premise of unknown pathological results. Various ultrasonic features of nodules were assessed objectively. The clinical features of components were determined by other physicians. Age, sex, unilateral or bilateral involvement of thyroid gland, lesion size, margin, shape, echogenicity, calcification, intranodular blood flow, cervical lymph node, and tumor node metastasis (TNM) stage were compared between MTC and PTC groups. Age, sex, involvement of the thyroid gland, margin, and calcification were similar for the MTC and PTC groups. Compared with the PTC group, the lesion size in the MTC group was significantly larger (P < 0.001). A taller-than-wide shape (aspect ratio > 1) was significantly less likely in the MTC group than the PTC group (P < 0.001). A mixed echogenicity was significantly more common in the MTC group than the PTC group (P = 0.003). The MTC group had significantly enhanced intranodular blood flow (P < 0.001). The TNM stage of the MTC group was significantly higher than that of PTC group (P = 0.001). Medullary thyroid carcinomas differ significantly from PTCs in lesion size, shape, echogenicity, and intranodular blood flow.

The amygdala is important in regulation of emotion-associated behavioral responses both to positive reinforcing stimuli such as addicting opioids and to negative aversive stimuli such as fear and pain. Glutamatergic neurotransmission in amygdala plays a predominant role in amygdala neuronal circuits involved in these emotional responses. However, how specific glutamate receptors act to mediate these amygdala functions remains poorly understood. In this study, we investigated the role of GluA1 subunits of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in central amygdala in modulating behavioral response to aversive stimuli by pain and by opioid withdrawal. We found that the protein level of GluA1 in the central nucleus of amygdala (CeA) was significantly increased in rats under persistent pain and viral upregulation of CeA GluA1 increased pain responses of both hyperalgesia and allodynia in rats. In contrast, the viral upregulation of CeA GluA1 inhibited, while knockdown of CeA GluA1 enhanced, place aversion induced by naloxone-precipitated morphine withdrawal. These results reveal a differential action of CeA GluA1 on the aversive event of sensory pain and opioid withdrawal, likely reflecting two distinct synaptic circuits of GluA1-predominant AMPA receptors within CeA for regulation of pain sensitivity and emotional response to opioid withdrawal.

The mechanism of the therapeutic action of antidepressants remains uncertain in traditional Chinese medicine (TCM). In this study, we selected 7 classical TCM prescriptions and utilised an automatic video-tracking system to monitor the rest/wake behaviour of larval zebrafish at 4 days post-fertilisation (dpf) for 48 hours. We found that the curative effects of the prescriptions were dose-dependent. K-means clustering was performed according to the shared behavioural phenotypes of the zebrafish. The results revealed that the rest/wake behavioural profiles induced by the same class of prescriptions were similar. A correlation analysis was conducted between the TCM prescriptions and the known compounds. The results showed that the TCM prescriptions correlated well with some well-known compounds. Therefore, we predicted that they may share a similar mechanism of action. This paper describes the first study to combine TCM research with zebrafish rest/wake behaviour in vivo and presents a powerful approach for the discovery of the mechanism of action of TCM prescriptions.