Intrathecal administration of adrenomedullin induces mechanical allodynia and neurochemical changes in spinal cord and DRG.
This study investigated the effect of adrenomedullin (AM) on mechanical pain sensitivity and its possible mechanisms. Intrathecal injection of AM receptor agonist AM1-50 (20 μg) once per day briefly reduced mechanical pain threshold on days 1 and 2 but induced prolonged mechanical allodynia on day 3. However, AM1-50 did not change mechanical pain sensation when the AM receptor antagonist AM22-52 (20 μg) was intrathecally co-administered. Daily administration of AM1-50 (20 μg) for 3 days increased expression of phosphorylated extracellular signal-regulated protein kinase (pERK) and neuronal nitric oxide synthase (nNOS) in the spinal dorsal horn. The AM-induced increase in pERK and nNOS was inhibited by the co-administration of AM22-52. The chronic administration of AM1-50 also increased expression of microglial maker Iba1 and astrocytic marker GFAP (glial fibrillary acidic protein) in the spinal dorsal horn in an AM22-52-sensitive manner. Furthermore, the application of AM1-50 (10 nM, 3 h) to dorsal root ganglion (DRG) explant cultures induced an increase in the expression of transient receptor potential vanilloid 1 (TRPV1). The treatment with AM1-50 did not change TRPV1 expression in DRG in the presence of AM22-52 (2 μM). These results suggest that the increased AM bioactivity induced mechanical allodynia and may contribute to the mechanical pain hypersensitivity under pathological conditions. The mechanisms may involve the activation of ERK signaling pathway and spinal glia as well as the recruitment of nNOS and TRPV1 in the spinal dorsal horn or DRG. The present study indicates that inhibition of the activation AM receptor might provide a fruitful strategy to relieving chronic pain.
['Huang|Hao|H|', 'Wang|Mei|M|', 'Hong|Yanguo|Y|']
D053607:Adrenomedullin D000818:Animals D002135:Calcium-Binding Proteins D002478:Cells, Cultured D004347:Drug Interactions D048049:Extracellular Signal-Regulated MAP Kinases D005727:Ganglia, Spinal D005904:Glial Fibrillary Acidic Protein D006930:Hyperalgesia D007278:Injections, Spinal D008297:Male D008840:Microfilament Proteins D052248:Nitric Oxide Synthase Type I D010147:Pain Measurement D010446:Peptide Fragments D010766:Phosphorylation D051381:Rats D013116:Spinal Cord D066148:Spinal Cord Dorsal Horn D050916:TRPV Cation Channels
Adrenomedullin (AM) pERK Spinal dorsal horn Dorsal root ganglion (DRG) Transient receptor potential vanilloid 1 (TRPV1) Glia