TLR4 and Pain: The lack of NOD1 and NOD2 affects the serotonergic signaling of gut and brain, the proliferation of hippocampal cells, and the maturation of neurons, which makes the mice lacking both of them vulnerable to HPA overactivation under stimulation, thus showing anxiety, cognitive impairment, and depression.378–380 TLR4 is very important in the process of neuropathic pain caused by infection and sterile neuronal injury.