There is growing evidence that opioids including fentanyl, as well as endogenous damage-associated molecular patterns (DAMPs) and peripheral inflammation associated with tissue damage from cancer or chemotherapy, can activate central innate immune cells (i.e. glia) via the toll-like receptor (TLR) family of pattern recognition receptors (e.g. TLR4) [8–11]. The gene discussed is TLR4; the disease is cancer.