N-methyl-D-aspartate Receptor Subunit 2B on Keratinocyte Mediates Peripheral and Central Sensitization in Chronic Post-ischemic Pain in Male Rats.

N-methyl-D-aspartate Receptor Subunit 2B on Keratinocyte Mediates Peripheral and Central Sensitization in Chronic Post-ischemic Pain in Male Rats. Brain Behav Immun. 2020 Feb 04;: Authors: Xu X, Tao X, Huang P, Lin F, Liu Q, Xu L, Xu J, Huang Y Abstract The spinal N-methyl-D-aspartate (NMDA) receptor, and particularly its NR2B subunit, plays a pivotal role in neuropathic pain. However, the role of peripheral NMDA receptor in neuropathic pain is less well understood. We first treated cultured human keratinocytes, HaCaT cells with NMDA or NR2B-specific antagonist, ifenprodil and evaluated the level of total and phosphorylated NR2B at 24h using Western blot. Next, using the chronic post-ischemia pain (CPIP) model, we administered NMDA or ifenprodil subcutaneously into the hind paws of male rats. Nociceptive behaviors were assessed by measuring mechanical and thermal withdrawal thresholds. Expression and phosphorylation of NR2B on keratinocyte were analyzed at 6, 12, 18, and 24 h on day 1 (initiation of pain) as well as day 2, 6, 10 and 14 (development and maintenance of pain) after the ischemia. The level of peripheral sensitization-related proteins (nuclear factor-κB (NF-κB), extracellular regulated protein kinases (ERK), and interleukin-1β (IL-1β)) in epidermis and dorsal root ganglion (DRG) were evaluated by immunofluorescence and western blot. Central sensitization-related C-fos induction, as well as astrocytes and microglia act...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research