The mesolimbic system plays a critical role both in modulating pain and mediating the response to opiates.This has been discussed in detail under General Description of the Overall Center. This system ofdopaminergic neurons that project from the ventral tegmental area (VTA) has been implicated in the rewardmechanism of opiates and is a focal point in the process of addiction (Koob and Le Moal, 2001; Nestler, 2004;Volkow et al., 2004; Nestler, 2005; Spanagel and Heilig, 2005). Moreover, a common attribute of drugs ofabuse is the release of dopamine in NAc. Adaptations within this system are believed to be a mechanism ofaddiction. Alterations within the dopaminergic system also have been found to be associated with pain statesin both animal and human imaging studies (Borsook and Becerra, 2006; Schweinhardt et al., 2006). Evidencefor the important role of striatal D2DR in modulating pain in humans has been reviewed recently by Hagelberget al. (Hagelberg et al., 2004). This convergence of brain regions and receptor system that impact upon bothmodulation of pain and the rewarding effects of drugs of abuse suggests the central hypothesis to be tested bythis proposal.
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