A multimodal disease modifying approach to treat neuropathic pain - inhibition of soluble epoxide hydrolase (sEH)

Both neuronal and non-neuronal mechanisms have been proposed to contribute to neuropathic pain (NP). All currently approved treatments for NP modulate neuronal targets and provide only symptomatic relief. Here we review evidence that inhibition of soluble epoxide hydrolase (sEH), the enzyme that degrades epoxyeicosatrienoic acids (EETs), has potential to be a multimodal, disease modifying approach to treat NP: (1) EET actions involve both endogenous opioid system and the GABAergic systems thus provide superior pain relief compared to morphine or gabapentin, (2) EETs are directly anti-inflammatory and inhibit expression of inflammatory cytokines and adhesion molecules thus can prevent continued nerve damage; and (3) EETs promote nerve regeneration in cultured neurons. Thus, an sEH inhibitor will not only provide effective pain relief, but would also block further nerve damage and promote healing.