GABAB receptor activation attenuates inflammatory orofacial pain by modulating interleukin-1β in satellite glial cells: Role of NF-κB and MAPK signaling pathways

Orofacial inflammation could activate satellite glial cells (SGCs) in the trigeminal ganglion (TG) to produce interleukin 1 beta (IL-1 beta) which plays crucial roles in the development of inflammatory pain. Recent studies have shown that gamma-amino butyric acid-B (GABA(B)) receptor could modulate the expression of inflammatory cytokines in microglia and astrocytes in the spinal cord. The objective of this study was to investigate whether GABA(B) receptors in TG SGCs attenuate inflammatory facial pain via mediating IL-1 beta following inflammation and its mechanisms. Complete Freund's adjuvant (CFA) was injected into the whisker pad of rats to induce inflammation in vivo. Lipopolysaccharide (LPS) was added to culture medium to activate SGCs in vitro. Behavioral measures showed that microinjection of baclofen (a selective GABA(B) receptor agonist) into the TG ameliorated the mechanical allodynia of CFA-treated rats. Interestingly, baclofen pretreatment inhibited SGC activation and IL-1 beta production, however, preserved the decreased expression of GABA(B) receptors in SGCs activated by CFA in vivo and LPS in vitro. In addition, baclofen suppressed the increased expression of p-NF- kappa B p65, p-I kappa B alpha, and p-p38 MAPK, while reversed the decreased production of I kappa B alpha, and further enhanced the increased expression of p-ERK(1/2) in LPS-treated SGCs in vitro. Finally, those effects of baclofen were abolished by saclofen (a specific GABA(B) receptor antagonist) co-administration. Altogether, these results demonstrated for the first time that activation of GABA(B) receptor might inhibit IL-1 beta production by suppressing NF- kappa B and p38 MAPK signaling pathway activation and restore GABA(B) receptor expression in SGCs to attenuate inflammatory facial pain