With dependence on opioids, such as codeine, morphine, and heroin, steadily increasing amongst the American public, the withdrawal symptoms associated with disuse are receiving much more attention. Our research identifies neurons that are implicated in the hyperanalgesic response to the cessation of opiate medication after dependence has been established. These neurons, identified by the cholecystokinin protein (CCK), are localized in regions of the central nervous system that are responsible for transducing painful signals from the periphery to the brain. In particular, our research focuses on the substantia gelatinosa of the spinal cord and the trigeminal nucleus within the brain stem; the spinal cord is responsible for transmitting painful signals from below the shoulders, and the trigeminal nucleus is responsible for transmitting pain from above the shoulders. Our research supports the hypothesis that neurons with high levels of CCK expression (CCK(+) neurons) are involved in the transmission of pain from the periphery, where the pain occurs, to the brain, where it is perceived. We did not find that the CCK(+) neurons communicate through GABA neurotransmission, and we will continue researching how these neurons communicate, as well as the implications they have on the modulation of pain by opiate use/disuse.