Cortical influences on brainstem circuitry responsible for conditioned pain modulation in humans.
Conditioned pain modulation (CPM) is a powerful endogenous analgesic mechanism which can completely inhibit incoming nociceptor signals at the primary synapse. The circuitry responsible for CPM lies within the brainstem and involves the subnucleus reticularis dorsalis (SRD). While the brainstem is critical for CPM, the cortex can significantly modulate its expression, likely via the brainstem circuitry critical for CPM. Since higher cortical regions such as the anterior, mid-cingulate, and dorsolateral prefrontal cortices are activated by noxious stimuli and show reduced activations during other analgesic responses, we hypothesized that these regions would display reduced responses during CPM analgesia. Furthermore, we hypothesized that functional connectivity strength between these cortical regions and the SRD would be stronger in those that express CPM analgesia compared with those that do not. We used functional magnetic resonance imaging to determine sites recruited during CPM expression and their influence on the SRD. A lack of CPM analgesia was associated with greater signal intensity increases during each test stimulus in the presence of the conditioning stimulus compared to test stimuli alone in the mid-cingulate and dorsolateral prefrontal cortices and increased functional connectivity with the SRD. In contrast, those subjects exhibiting CPM analgesia showed no change in the magnitude of signal intensity increases in these cortical regions or strength of functional connectivity with the SRD. These data suggest that during multiple or widespread painful stimuli, engagement of the prefrontal and cingulate cortices prevents the generation of CPM analgesia, raising the possibility altered responsiveness in these cortical regions underlie the reduced CPM observed in individuals with chronic pain. Hum Brain Mapp 37:2630-2644, 2016. © 2016 Wiley Periodicals, Inc.
Department of Anatomy and Histology, University of Sydney, Sydney, 2006, Australia.
Andrew M
AM
Youssef
School of Medicine, Western Sydney University, Sydney, Australia.|Neuroscience Research Australia, Sydney, Australia.
Vaughan G
VG
Macefield
Department of Anatomy and Histology, University of Sydney, Sydney, 2006, Australia.
Luke A
LA
Henderson
D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D001933:Brain Stem / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000503:physiopathology*; D005260:Female; D006358:Hot Temperature; D006801:Humans; D008046:Lip; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000503:physiopathology; D010146:Pain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D058748:Pain Perception / Q000502:physiology*; D011601:Psychophysics; D055815:Young Adult
cingulate cortex; diffuse noxious inhibitory control; dorsolateral prefrontal cortex; endogenous analgesia; subnucleus reticularis dorsalis