Scheme 1.

Schematic illustration of the potential mechanisms by which N-butanoyl-2-(2-methoxy-6H-isoindolo[2,1-a]indol-11-yl)ethanamine (IIK-7) modulates pain. The extent of neuroinflammation in neuropathic pain depends on the two-way interactions between neurons and immune cells. According to current literature, microglia are the important cells that mediate neuronal inflammation at the spinal cord level after axotomy. Though microglial are known to be key cells involved in NP, their mechanisms of activation remain elusive. Current evidence indicates that reactive oxygen species (ROS) stimulate the activation. In the present study, we have shown, for the first time, that infusion of IIK-7 prevents microglial cell activation in partial sciatic nerve-transected rats. Simultaneously, IIK-7 treatment affects directly and/or indirectly intracellular pathways, which play a key role in regulating the immune response cascade: STAT3, CASP-3, HMGB-1 and iNOS proteins. These molecular actions of IIK-7 might be responsible for its analgesic effect during neuropathic pain and need future investigation.

Abbreviations: IIK-7, N-Butanoyl 2-(9-methoxy-6H-iso-indolo[2,1-a]indol-11-yl)-ethan-amine; P44/42 MAPK, P44/42 mitogen-activated protein kinase; iNOS, inducible nitric oxide synthase; ROS, reactive oxygen species; STAT3, Signal transducer and activator of transcription 3; CASP-3, caspase3; HMGB-1, High mobility group box 1.