Dopamine Dependence of Offset Analgesia

Offset analgesia is a psychophysical phenomenon characterized by a transient, disproportionately large decrease in pain following a slight reduction in noxious stimulus intensity. This phenomenon is both mechanistically and clinically interesting. Mechanistically, it uncouples a noxious stimulus from pain qualia-two often-conflated constructs. Clinically, it is blunted in patients with chronic pain, making it a biomarker for chronic pain. Yet, we do not understand how offset analgesia occurs. By elucidating offset analgesia's mechanisms, we will gain a greater understanding of the nociceptive-pain circuitry. Moreover, it would transmute offset analgesia from a psychophysical correlate of chronic pain to a biomarker that provides neurophysiological insight. This project will investigate the dopaminergic basis of offset analgesia using fMRI and pharmacological perturbations.The fMRI portion of this work will investigate the correlative role of nucleus accumbens in offset analgesia. If the mesolimbic system is responsible for offset analgesia, its dynamics should capture the temporal dissociation between the noxious stimulus (temperature) and pain ratings.In the pharmacological portion of this work, we will administer methylphenidate or placebo (double-blinded, within-subject, crossover trial) to assess the effects of increased dopamine availability on offset analgesia's dynamics.

Inclusion Criteria:-Exclusion Criteria:PregnantHistory of chronic painHistory of neurological diagnosisHistory of psychiatric diagnosis