Mol Pain
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Pain involves both sensory and affective dimensions. The amygdala is a key player in linking nociceptive stimuli to negative emotional behaviors or affective states. Relief of pain is rewarding and activates brain reward circuits. ⋯ Activation of the VTA-CeA neural pathway using optogenetic approaches relieved incisional pain. Administration of a D2 receptor agonist reversed the pain relief elicited by light-induced activation of the VTA-CeA pathway. These findings indicate that the VTA-CeA circuit is involved in pain relief in mice via dopamine receptor D2 in the CeA.
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Can mice recognize themselves in a mirror? The answer is unclear. Previous studies have reported that adult mice - when shown itch-like videos - demonstrated itch empathy. However, this was proven to be unreproducible in other studies. ⋯ Differently, in the case of chemical pain (formalin injection), animals' nociceptive responses to formalin during Phase II were significantly enhanced in the mirrored open field. A new format of heat map was developed to help the analysis of the trace of mice in the open field. Our results suggest that mice do recognize the presence of mice in the mirror, and their nociceptive - but not itch - responses are enhanced.
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Background: Accumulating evidence shows that N6-methyladenosine (m6A) modulators contribute to the process of chronic pain. However, the exact mechanisms of m6A writers involved in visceral hypersensitivity of Irritable bowel syndrome (IBS) remain unclear. This article aimed to reveal a new mechanism for the progression of IBS. ⋯ Moreover, YTHDC1, the only m6A-associated protein predicted by bioinformatics to bind to circKcnk9, modulated visceral hypersensitivity through regulating the nuclear export of circKcnk9 in an m6A-dependent manner. Notably, FISH data suggested that the increased nuclear staining of circKcnk9 caused by siYTHDC1 could be recovered by overexpression of YTHDC1 wild type (WT) but not YTHDC1 negative control (NC) in PC12 cells. Conclusions: Our findings reveal a new regulatory mechanism in progress of IBS, that is, METTL3 modulates visceral hypersensitivity through regulating the nuclear export of circKcnk9 in YTHDC1-dependent manner.
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DNA hydroxylation catalyzed by Tet dioxygenases occurs abundantly in neurons in mammals. However, effects of ten-eleven translocation methylcytosine dioxygenase 1 (TET1) expression and hydroxymethylation status on neuron injury remain unclear. This study was designed to explore the effects of TET1 and TET2 expression in the inflammatory pain of rats induced by complete Freund's adjuvant (CFA). ⋯ Intrathecal administration of Bobcat339 improved mechanical and thermal pain threshold in CFA rats. Our findings highlight the role of TET1 in chronic inflammatory pain model. The expression of TET1 was increased in CFA rats, and suppression of TET1 will ameliorate inflammatory pain.
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Osteoarthritis (OA) is a common osteoarthropathy with chronic inflammatory pain as the core symptom in middle-aged and elderly people. LncRNA MEG3 (Maternally expressed gene 3) is involved in the development of OA via regulation of angiogenesis, which causes the activation and overexpression of transient receptor potential vanilloid type-1 (TRPV1). In this study, we investigated the mechanism of MEG3-TRPV1 signaling in chronic inflammatory pain (CIP) of rat model. ⋯ Treatment with a TRPV1 antagonist also significantly relieved chronic inflammatory pain in CFA-induced rats. In general, our results reveal that MEG3 alleviates chronic inflammatory pain by downregulating TRPV1 expression. These findings may provide new therapeutic targets in the treatment of patients with OA.