FIGURE 2.

Barriers to understanding the role of presynaptic N-methyl-D-aspartate receptors (preNMDARs) in superficial dorsal horn (SDH) nociception. (A). Existing literature on preNMDARs in the SDH spans several developmental timepoints. This makes comparison between studies problematic, as NMDAR expression and composition may change throughout development. (B). Almost all studies on preNMDARs in the SDH have been conducted in male or unsexed animals. Because data in recent years has demonstrated substantial sex differences in not only pain and nociception, but in the role of NMDARs in pain, it is critical for future studies to examine preNMDARs in females. (C). The complex circuitry and unknown connectivity of the SDH makes interpreting overall output from the contributions of preNMDARs difficult. Increased mapping of the connectivity of distinct neuronal subpopulations, such as primary afferent terminals, inhibitory and excitatory interneurons, as well as projection neurons, in addition to understanding the distinct contributions of axo-dendritic and axo-axonic connections, will be vital to fully understand the role of preNMDARs in nociception in the SDH. Figure was created using BioRender.com.