Fig. (4). CaMKIV distinguishes fear memory and chronic pain.

Inflammatory or nerve injuries trigger the release of excitatory neurotransmitter glutamate, and activation of NMDAR leads to an increase in postsynaptic Ca²⁺. Ca²⁺ binds to CaM and leads to activation of Ca²⁺/CaM-dependent protein kinases, such as CaMKIV. In the absence of CaMKIV, fear memory was significantly reduced but behavioral responses to painful stimuli remained unchanged, indicating that fear memory and pain may be dissociated at the molecular level.