Figure 2.

Neuro-immune interaction contributing to the establishment of pain during AKI. The figure shows the injured kidney secreting the immune cells and mediators that induce peripheral sensitization of nociceptor sensory neurons leading to pain. During inflammation induced by the injury, there is a loss of the cell architecture of the kidney tissues. This leads to release of specific immune cells, signal mediators, growth factors and inflammatory mediators. Together the influx of these cells leads to phosphorylation and/or gating of sodium ion channels Na_v1.7, Na_v1.8, Na_v1.9, as well as the cation channels TRPV1, summing up to increased peripheral sensitization by action potential generation via calcium signaling. The Prostaglandin E₂ (PGE₂) also act via their receptors (EP1–4) to aid in peripheral sensitization by similar path. The tumor necrosis factor alpha (TNF-α) and IL-1β produced by mast cells, macrophages, and neutrophils also sensitize nociceptors mainly via calcium signaling. The same route is followed by NGF and GPCR signaling which act on the calcium channels. Along with these, the High mobility group box 1 protein (HMGB1) also activates the toll like receptors and increases expression of TRPV1 which mediates the pain signaling. The drugs used against pain in AKI have also been included.