Nerve injury sensitizes a pronociceptive signaling pathway that is tonically silenced by endogenous pain inhibitory NPY-Y1 activity: NMDAR → AC1 → TRPA1/V1. In this model, a Y1 receptor antagonist or NPY knockdown suppresses NPY-Y1, leading to disinhibition of pronociceptive neurotransmitter release, spinal neuron excitability and, ultimately, pain. Line Arrows denote activation/production; Line Dot denotes inhibition.