Pain and Motivated Behavior
Pain provides a useful protective role; through avoidance learning, pain helps to decrease the probability of engaging in tissue-damaging, or otherwise dangerous experiences. However, pain is frequently accompanied by negative affective states. In conditions of chronic pain, despair and depression may lead to life threatening events, such as suicidality. Thus, dissecting the neuronal mechanisms responsible for the development of negative affective states represents an important step in improving the treatment of the emotional component of pain.
In addition to the development of negative affective states, recent reports demonstrate that 25% of patients experiencing pain misuse drugs of abuse, a maladaptive behavior that can lead to involuntary overdose and/or addiction. Indeed, despite their extremely efficacious treatment for severe and acute pain, opioid analgesics possess a high misuse liability. As the opioid epidemic in the US continues to worsen, it is critical that we determine the factors and neuronal adaptations in specific brain circuits to develop novel strategies to tackle the co-occurrence of pain and negative affective states that can ultimately lead to opioid misuse.
The mesolimbic pathway, composed of the ventral tegmental area (VTA) and the nucleus accumbens (NAc) areas, represents a central hub for the processing of both rewarding and aversive stimuli. In patients afflicted by either pain, substance use disorder, or depression this dopaminergic pathway is dysregulated. Indeed, dopamine release in the NAC from VTA neurons is strongly decreased in afflicted patients. Numerous laboratories have described a crucial role for the opioid systems in controlling dopaminergic function in both physiological and pathological conditions. However, the mechanisms underlying dopaminergic function dysregulation in conditions of pain driving negative affective states or misuse liability remain to be determined.
One of the goals of our laboratory is to dissect the molecular and neural mechanisms underlying pain-induced adaptations in central opioid systems in order to understand how pain conditions drive negative affect which may result in opioid seeking behavior.