Mol Pain
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Cyclin dependent kinase 5 (Cdk5) is a key neuronal kinase whose activity can modulate thermo-, mechano-, and chemo-nociception. Cdk5 can modulate nociceptor firing by phosphorylating pain transducing ion channels like the transient receptor potential vanilloid 1 (TRPV1), a thermoreceptor that is activated by noxious heat, acidity, and capsaicin. TRPV1 is phosphorylated by Cdk5 at threonine-407 (T407), which then inhibits Ca2+ dependent desensitization. ⋯ However, behavioral tests showed that the TRPV1T407A knock-in mice have reduced aversion to oral capsaicin along with a trend towards decreased facial displays of pain after a subcutaneous injection of capsaicin into the vibrissal pad. In addition, the TRPV1T407A mice display basal thermal hypoalgesia with increased paw withdrawal latency while tested on a hot plate. These results indicate that phosphorylation of TRPV1 by Cdk5 can have important consequences on pain perception, as loss of the Cdk5 phosphorylation site reduced capsaicin- and heat-evoked pain behaviors in mice.
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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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Bone cancer pain (BCP) is a clinically intractable mixed pain, involving inflammation and neuropathic pain, and its mechanisms remain unclear. CXC chemokine receptor 1 (CXCR1, IL-8RA) and 2 (CXCR2, IL-8RB) are high-affinity receptors for interleukin 8 (IL8). According to previous studies, CXCR2 plays a crucial role in BCP between astrocytes and neurons, while the role of CXCR1 remains unclear. ⋯ Intrathecal injection of CXCR1-siRNA reduced phosphorylated JAK2/STAT3 protein levels and the NLRP3 inflammasome (NLRP3, caspase1, and IL-1β) levels. Furthermore, in vitro cytological experiments confirmed this conclusion. The study results suggest that the spinal chemokine receptor CXCR1 activation mediates BCP through JAK2/STAT3 signaling pathway and NLRP3 inflammasome (NLRP3, caspase1, and IL-1β).
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Spinal neuroinflammation plays a critical role in the genesis of neuropathic pain. Accumulating data suggest that abscisic acid (ABA), a phytohormone, regulates inflammatory processes in mammals. In this study, we found that reduction of the LANCL2 receptor protein but not the agonist ABA in the spinal cord is associated with the genesis of neuropathic pain. ⋯ These changes are ameliorated when ABA is added with LPS. The anti-inflammatory effects induced by ABA do not requires Gi protein activity. Our study reveals that the ABA/LANCL2 system is a powerful endogenous system regulating spinal neuroinflammation and nociceptive processing, suggesting the potential utility of ABA as the management of neuropathic 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.