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Identification of Phylogenic Sequences Associated with Neuropathic Pain

Neuropathic pain refers to pain arising from nerve damage and tends to follow a chronic trajectory with minimal treatment options. Understanding phylogenic sequences implicated in neuropathic pain could serve to inform early identification of risk and treatment options. To that end, Dr. Lei Yu, Professor in the Center of Alcohol and Substance Use Studies in collaboration with researchers at Kent State University have identified a phylogenic sequence that may be implication in experiences of neuropathic pain. SIP30 has previously been implicated in synaptic vesicle regulation and pain following nerve injury. As such, this research team sought to analyze phylogenic sequences from primates, humans, rodents, and domesticated animals to evaluate divergences in SIP30 and its binding partners, SNAP25 and ZW10 as they relate to neuropathic pain.  Phylogenic trees were constructed to identify variations in SIP30. Further, the researchers sought to identify coiled-coil domains present in SIP30 that serve as a marker of the proteins ability to effectively interact with other proteins. Findings of this work demonstrate that when SIP30 is inhibited, subsequent stimulated exocytosis is inhibited. Phylogenic sequences of SIP30 demonstrated greater divergence compared to SW10 and SNAP25. Notably, sequences were conserved across species, however, primates (including humans) demonstrated great divergence in the coiled-coil domain suggesting that primates accumulate mutations at a faster rate. Taken together, this work adds to the existing knowledge on neuropathic pain and reinforces SIP30 as a potential treatment target.

The full article can be accessed here: https://www.sciencedirect.com/science/article/pii/S2405580823002121

Guo, N., Raincrow, J., Chiu, C. H., & Yu, L. (2024). Phylogenetic analysis of mammalian SIP30 sequences indicating accelerated adaptation of functional domain in primates. Biochemistry and Biophysics Reports37, 101631.