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.