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Papers of the Week

Papers: 12 Mar 2022 - 18 Mar 2022

Animal Studies

2022 Mar 16


Evaluation of chiral N,N-dimethyl-sphingosine for the interaction between nerve growth factor and tropomyosin receptor kinase A.


Murai Y, Sekiguchi A, Hirakawa T, Usuki S, Igarashi Y, Monde K
Chirality. 2022 Mar 16.
PMID: 35297105.


Neuropathic pain is an unbearable condition caused by nervous system damage. As distinct acute pain, neuropathic pain is chronic, and it severely influences quality of life. N,N-Dimethyl-d-erythro-sphingosine (DMS), a neuropathic pain inducer, is metabolited de novo from sphingosine. In a recent study, metabolomics showed an increased concentration level of DMS in the spinal cord in mice with neuropathic pain. Nerve growth factor (NGF) is one of the peripheral nervous system targeted pain factors that interact with tropomyosin receptor kinase A (trkA). On the basis of this information, we were interested in the possibility that DMS may induce neuropathic pain-like behavior through an increase of NGF activity. In this study, we showed that DMS can enhance the binding of NGF to trkA, followed by neurite outgrowth of epidermal nerve fibers and phosphorylation of trkA. In addition, a stereoisomer, N,N-dimethyl-l-erythro-sphingosine, did not any show such biological activities. The results suggest that DMS can enhance the binding of NGF to trkA and that its stereochemistry is an essential factor for exhibiting its activity.