Supplementary Material About Discussion

Supplementary material about discussion

To facilitate the understanding of our findings in processing nociceptive transmission, we make a discussion as follows:

From our study, we hypothesized three different potential neurophysiological interactions among EM2, SP, and GABA in the spinal dorsal horn. The first possibility is that EM2 presynaptically inhibits SP release from the primary afferent terminals and also facilitates the presynaptic inhibitory effect of GABAergic neurons in the spinal dorsal horn following primary afferent nociceptive stimulation, which enhances the analgesic effects of EM2. The second possibility is that the up-regulation of SP in the primary afferents after noxious stimulation may partly counteract or balance the analgesic effect of EM2 in the same terminal, while EM2 may down-regulate the postsynaptic release of GABA in the GABAergic interneurons synchronously, which results in facilitating nociceptive transmission to the supraspinal brain area via GABAergic disinhibition mechanisms. The third possibility is that there is no observable difference in the effect of EM2 between SP and GABAergic neurons on the modulation of nociceptive transmission in the dorsal horn; although both EM2 and SP have close contact with GABAergic neurons, each of them may play its own role in nociceptive transmission and modulation. All these possibilities and the synaptic connections between EM2 and SP co-localized fibers and terminals and GABAergic inhibitory interneurons need to be further studied.