The enzyme soluble epoxide hydrolase (sEH) regulates the levels of a group of potent bioactive lipids, the so called epoxygenated fatty acids (EFAs). These fatty acids have a variaty of biological functions.

The arachidonic acid derived epoxy eicosatrienoic acids (EETs) for instance are established autocrine and paracrine messengers. Recently it has been demonstrated that  inhibition of sEH leads to increased EFAs and reduction of pain.  ^[1]

There are a number of other physiological functions of EETs including angiogenesis, neurohormone release, cell proliferation, hypertension G protein signaling, modulation of ion channel activity, and a variety of effects associated with modulation of NFkappaB. ^[2][3] Many of these important biological effects can be modulated by sEHIs but also by natural occuring eicosanoids which offer new therapeutic possibilities.^[4] 

Inhibitors of sEH block both inflammatory and neuropathic pain and elevation of EFAs, in both the nervous systems, blocks pain. Other lipids such as the Cannabinoids also excert anti-neuropathic pain effects and recently one of these naturally occuring lipids, was found to be effective in neuropathic pain studies. ^[5][6]

Jan M. Keppel Hesselink, MD, PhD, october 2010 

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