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  • In this study we find that DH CBD induces


    In this study, we find that DH-CBD induces analgesic effects on inflammatory but not acute pain and the mibefradil australia level of spinal α1 GlyRs increased after CFA paw injection. These results suggest that GlyR α1 is only involved in chronic pain. A possible explanation is that once the expression of α1 GlyRs increases during the progress of chronic inflammatory pain, the cannabinoid potentiation of α1 GlyRs is probably sufficient to inhibit excitability of the spinal cord neurons in charge of pain signal transmission and therefore induces analgesic effects. Consistently, similar phenomena regarding acute versus inflammatory pain were also observed in K/O mice in the previous pain research. For instance, the transient receptor potential cation channel subfamily V member 1 (TRPV1), protein kinase C (PKC) or microsomal prostaglandin E synthase-1 (mPGES-1) K/O mice only showed altered responses to inflammatory or neuropathic pain, but not acute pain (MalmbergCC et al., 1997, Bolcskei et al., 2005, Kamei et al., 2004, Pogatzki-Zahn et al., 2005). Consistent with this study, some previous studies also observed an increased level of these key proteins, such as TRPV1 and PKC, in the CNS after inflammation (Cheng et al., 2008, Pogatzki-Zahn et al., 2005, Yu et al., 2008). Additionally, the above-mentioned feature of DH-CBD makes it a competitive candidate analgesic as it can specifically relieve the chronic inflammatory pain without impairing the normal transmission of sensory information.
    Conflicts of interest
    Acknowledgements We acknowledge support from the National Key Research and Development Program of China (2016YFC1300500-2), National Natural Science Foundation of China (Grants 31471014, 91432103, 91649121), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant XDB02010000), the Fundamental Research Funds for the Central Universities, the Major/Innovative Program of Development Foundation of Hefei Center for Physical Science and Technology, and Recruitment Program of Global Experts, and the National Institutes of Health (Grant AA10422).
    Introduction There are many amino acids in the human body, some of which function as neurotransmitters in the central mibefradil australia nervous system (CNS). β-alanine (β-amino acid) is an endogenous small amino acid and a structural analog of the major inhibitory neurotransmitters, glycine (α-amino acid) and γ-gamma aminobutyric acid (GABA, γ-amino acid) [1]. Fig. 1 shows that the structural formulae of these three amino acids are very simple and similar, with only differences in the number of carbon chains. β-alanine is present in blood, organs, muscles, the CNS [[1], [2], [3]]. β-alanine can act as a neuromodulator [3] or neurotransmitter, like glycine and GABA [4], in the CNS. β-alanine is released following electrical stimulation in the rat neocortex [5] and medulla oblongata [6], and rabbit superior colliculus [4]. β-alanine pharmacologically activates glycine and GABAA receptors with less efficacy than their native ligands in the brain [7,8]. Additionally, β-alanine decreases glutamatergic excitation by binding to the glycine co-agonist site on the N-methyl-d-aspartate receptor [9,10]. These dual effects of β-alanine are unique, and contribute to neuroprotective action in the hippocampus [11] and visual information transmission in the retina [4,12]. Autoradiography studies show that β-alanine is localized in neurons and glial cells in the spinal cord [13]. Studies indicate that β-alanine plays an important role in the spinal cord [14,15]. Intrathecal β-alanine decreased vocalizations and skin hyperalgesia triggered by intrathecal administration of strychnine in rats [14]; however, another study reported that β-alanine did not reduce allodynia and hyperalgesia caused by strychnine in mice [15]. β-alanine inhibits the firing of spinal cord neurons in frogs, chicks, mice, and cat, which has been attributed to an increase in Cl− and/or K+ conductance in the neuronal membrane of spinal cord [[16], [17], [18], [19]].