Anti­inflammatory actions of gabapentin and pregabalin on the substance P­induced mitogen­activated protein kinase activation in U373 MG human glioblastoma astrocytoma cells.

ABSTRACT

Gabapentin (GBP) and pregabalin (PGB) exert antinociceptive effects on chronic nociceptive responses with neuropathic or inflammatory conditions. Furthermore, it is considered that GBP and PGB exhibit anti­inflammatory effects by modulating the substance P (SP)­mediated neurokinin­1 receptor (NK1R; a SP receptor) response. Thus, in the present study, the effects of GBP and PGB on SP­induced activation were investigated in the human glioblastoma astrocytoma U373 MG cell line, which expresses high levels of functional high­affinity NK1R, and produces interleukin (IL)­6 and IL­8 in response to SP. The results indicated that GBP and PGB suppressed the SP­induced production of IL­6, and IL­8 in U373 MG cells. Furthermore, GBP and PGB inhibited the SP­induced phosphorylation of p38 mitogen­activated protein kinase (MAPK) and nuclear factor (NF)­κB, and the nuclear translocation of NF­κB in U373 MG cells. Together, these observations suggest that GBP and PGB likely prevent SP­induced IL­6 and IL­8 production in U373 MG cells via the inhibition of signaling molecules, including p38 MAPK and NF­κB, thereby exhibiting antineuroinflammatory effects.