Simultaneous fMRI–PET of the opioidergic pain system in human brain

Abstract

MRI and PET provide complementary information for studying brain function. While the potential use of simultaneous MRI/PET for clinical diagnostic and disease staging has been demonstrated recently; the biological relevance of concurrent functional MRI-PET brain imaging to dissect neurochemically distinct components of the blood oxygenation level dependent (BOLD) fMRI signal has not yet been shown. We obtained sixteen fMRI-PET data sets from eight healthy volunteers. Each subject participated in randomized order in a pain scan and a control (nonpainful pressure) scan on the same day. Dynamic PET data were acquired with an opioid radioligand, [11C]Diprenorphine, to detect endogenous opioid releases in response to pain. BOLD fMRI data were collected at the same time to capture hemodynamic responses. In this simultaneous human fMRI-PET imaging study, we show co-localized responses in thalamus and striatum related to pain processing, while modality specific brain networks were also found. Co-localized fMRI and PET signal changes in the thalamus were positively correlated suggesting pain-induced changes in opioid neurotransmission contribute a significant component of the fMRI signal change in this region. Simultaneous fMRI-PET provides unique opportunities allowing us to relate specific neurochemical events to functional hemodynamic activation and to investigate the impacts of neurotransmission on neurovascular coupling of the human brain in vivo.

Endogenous opioidergic dysregulation of pain in fibromyalgia: a PET and fMRI study

“…30 The only other pain studies we are aware of that employed PET and fMRI together were performed in healthy individuals and used the non-selective radioligand ([ 11 C]diprenorphine). 16; 64 Our study is also the first to perform a whole brain search specifically correlating fMRI BOLD responses to pain with resting MOR BP. Our findings suggest that the dysregulation of the endogenous opioid system we previously reported in these FM patients is strongly related to an objective neural marker of their pain sensitivity.…”

The altered right frontoparietal network functional connectivity in migraine and the modulation effect of treatment

“…A previous study 58 showed that pain relief could produce negative reinforcement through activation of the mesocorticolimbic reward-valuation circuitry. A recent human fMRI-PET study 59 found that increased endogenous opioid releases were at nucleus accumbens during pressure pain. Taken together, our results suggest that the cognitive control network, reward system, and descending pain modulatory network may all be involved in the modulation process of acupuncture treatment.…”

News and views on in-vivo imaging of neurotransmission using PET and MRI

“…In a study that investigated pain modulation, simultaneously co-localized fMRI and PET signal changes with the opioid-ligand [ 11 C]diprenorphine were found in the thalamus and striatum. The positive correlation between thalamic changes in binding potential and magnitude of BOLD signal change suggests that pain-induced changes in opioid receptor binding directly contributes to the fMRI signal change in this region 90 . Other studies have investigated sequentially obtained PET receptor availability and fMRI signal in the same subjects: In the context of the opioid receptor system, BOLD response patterns due to watching movie clips of painful situations were shown to be correlated with μ-opioid receptor availability, as measured with [ 11 C]carfentanil, but not with D2 receptor availability, as measured with [ 11 C]raclopride 109 , suggesting the involvement of the opioid system, but not the dopamine system in vicarious pain.…”

“…Thus, the postulated role of the opioid system in mediating the effects of amphetamine needs to be further investigated. To assess whether such pain-induced changes in opioid neurotransmission contribute a significant component of the blood oxygenation level dependent (BOLD) functional MRI signal, simultaneous PET/MRI has been performed using [ 11 C]diprenorphine and dynamic data acquisition 90 . This study showed co-localized responses in thalamus and striatum related to pain processing indicating a correlation between opioid release and functional hemodynamic activation during pain.…”