Sheng li xue bao : [Acta physiologica Sinica]
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This study was aimed to investigate the mechanisms of the modulation effect of activation of spinal Mas-related gene C (MrgC) receptors on hyperalgesia induced by intraplantar (i.pl.) injection of (Tyr6)-γ2-MSH-6-12 (MSH) or complete Freund's adjuvant (CFA). Paw withdrawal latency test and immunohistochemistry were used to observe the effect of intrathecal (i.t.) administration of MSH or BAM8-22, two selective agonists of MrgC receptor, in hyperalgesia in rats. The results showed that i.t. administration of MSH inhibited acute hyperalgesic response induced by i.pl. application of MSH, while did not change thermal nociceptive threshold in naïve rats. ⋯ The i.t. injection of BAM8-22 at a dose of 30 nmol evidently reduced the number of CFA-evoked nitric oxide synthase (NOS)-positive neurons and the expression of calcitonin gene-related peptide (CGRP)-immunoreactivity positive nerve fibers at L3-L5 segments of the spinal cord. These results suggest that the activation of MrgC receptor in CFA-induced inflammation reduces inflammatory hyperalgesia through inactivation of NOS neurons and down-regulation of CGRP expressions, and generates delayed but long-lasting anti-nociception through the endogenous activation of MOR via indirect mechanisms. Agonists for MrgC receptors may, therefore, represent a new class of antihyperalgesics for treating inflammatory pain because of the highly specific expression of their targets.
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Review
[Involvement of adrenomedullin in the pathogenesis of inflammatory pain and morphine tolerance].
The increase of pronociceptive mediators in the dorsal root ganglia (DRG) and spinal dorsal horn is an important mechanism in the pathogenesis of inflammatory pain and opioid tolerance. Adrenomedullin (AM) belongs to calcitonin gene-related peptide (CGRP) family and has been recently demonstrated to be a pain-related peptide. ⋯ The present review highlights the recent developments regarding the involvement of AM in these two disorders. The neurological mechanisms of AM's actions are also discussed.