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.
Phase:
Phase 2
Details
Lead Sponsor:
Northwestern University
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)