Schematics of proposed mechanisms underlying BGJTD- or BeD-modulated pain responses. According to our data, signaling of TNF-α and TrkB appeared to increase after nerve ligation (a). TNF-α, which were decreased by BGJTD treatment, may cause weakening in retrograde signaling of TNFR into the cell body, leading to alleviating pain response (b). After BeD treatment, p-Erk1/2 and IL-6 signals, induced from Schwann cells and macrophages, may transmit the signals of IL-6R into the neuronal cell body (soma), inducing JAK/STAT activation and regulation of target gene expression including the repression of TrkB gene expression (c). Consequently, retrograde TrkB signaling would be attenuated and lead to alleviate pain response.