Serotonin transporter binding in the hypothalamus correlates negatively with tonic heat pain ratings in healthy subjects: A [11C]DASB PET study

Kupers, Ron; Frøkjær, Vibe G.; Erritzoe, David; Naert, Arne; Budtz-Joergensen, Esben; Nielsen, Finn Årup; Kehlet, Henrik; Knudsen, Gitte M.

doi:10.1016/j.neuroimage.2010.09.010

Cited by 29 publications

(24 citation statements)

References 61 publications

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“…Although there is a study that reported the relationship between pain and 5-HTT in the human brain using PET (Kupers et al, 2011), it is not clear how 5-HTT is related to the analgesic effect. More recently, it was reported that emotion and pain are closely linked through the 5-HT system (Bushnell et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Occupancy of serotonin transporter by tramadol: a positron emission tomography study with [11C]DASB

Ogawa

Tateno

Arakawa

et al. 2014

Int. J. Neuropsychopharm.

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Tramadol is used for the treatment of pain, and it is generally believed to activate the μ-opioid receptor and inhibit serotonin (5-HT) and norepinephrine (NE) transporters. Recent findings from animal experiments suggest that 5-HT reuptake inhibition in brain is related to pain reduction. However, there has been no report of 5-HT transporter (5-HTT) occupancy by tramadol at clinical doses in humans. In the present study, we investigated 5-HTT occupancy by tramadol in five subjects receiving various doses of tramadol by using positron emission tomography (PET) scanning with the radioligand [11C]DASB. Our data showed that mean 5-HTT occupancies in the thalamus by single doses of tramadol were 34.7% at 50 mg and 50.2% at 100 mg. The estimated median effective dose (ED50) of tramadol was 98.1 mg, and the plasma concentration was 0.33 μg/ml 2 h after its administration; 5-HTT occupancy by tramadol was dose-dependent. We estimated 5-HTT occupancy at 78.7% upon taking an upper limit dose (400 mg) of tramadol. The results of the present study support the finding that 5-HTT inhibition is involved in the mechanism underlying the analgesic effect of tramadol in humans, and a clinical dose of tramadol sufficiently inhibits 5-HTT reuptake; this inhibition is similar to that shown by selective serotonin reuptake inhibitors (SSRIs).

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Section: Discussionmentioning

confidence: 99%

Occupancy of serotonin transporter by tramadol: a positron emission tomography study with [11C]DASB

Ogawa

Tateno

Arakawa

et al. 2014

Int. J. Neuropsychopharm.

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“…SERT binding in the hypothalamus was observed to be negatively associated with pain (Kupers et al 2011), while cognitive functioning was found to be positively correlated to SERT levels in right dorsolateral PFC, caudate and left ventrolateral PFC (Madsen et al 2011a). Another negative association was found between SERT binding in the thalamus and stress and anxiety (Ichise et al 2006;Reimold et al 2011).…”

Section: Transportersmentioning

confidence: 96%

Serotonin and molecular neuroimaging in humans using PET

2011

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The serotonergic system is one of the most important modulatory neurotransmitter systems in the human brain. It plays a central role in major physiological processes and is implicated in a number of psychiatric disorders. Along with the dopaminergic system, it is also one of the phylogenetically oldest human neurotransmitter systems and one of the most diverse, with 14 different receptors identified up to this day, many of whose function remains to be understood. The system's functioning is even more diverse than the number of its receptors, since each is implicated in a number of different processes. This review aims at illustrating the distribution and summarizing the main functions of the serotonin (5-hydroxytryptamin, 5-HT) receptors as well as the serotonin transporter (SERT, 5-HTT), the vesicular monoamine transporter 2, monoamine oxidase type A and 5-HT synthesis in the human brain. Recent advances in in vivo quantification of these different receptors and enzymes that are part of the serotonergic system using positron emission tomography are described.

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“…However, the expression of SERT in the hypothalamus was poorly defined as spatial resolution of nuclear imaging techniques is limited, and delineation of a structure as small and heterogeneous as the hypothalamus is cumbersome with conventional region-of-interest (ROI) analysis [20]. To our knowledge, only one study demonstrated hypothalamic SERT binding using PET and [ 11 C]DASB, although the delineation of the hypothalamus was not strictly defined [21]. …”

Section: Introductionmentioning

confidence: 99%

Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

et al. 2013

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BackgroundSerotonergic neurons in the rodent hypothalamus are implicated in key neuroendocrine and metabolic functions, including circadian rhythmicity. However, the assessment of the serotonergic system in the human hypothalamus in vivo is difficult as delineation of the hypothalamus is cumbersome with conventional region-of-interest analysis. In the present study, we aimed to develop a method to visualize serotonin transporters (SERT) in the hypothalamus. Additionally, we tested the hypothesis that hypothalamic SERT binding ratios are different between patients with hypothalamic impairment (HI), pituitary insufficiency (PI), and control subjects (C).MethodsSERT availability was determined in 17 subjects (6 HI, 5 PI, and 6 healthy controls), 2 h after injection of 123I-N-ω-fluoropropyl-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ([123I]FP-CIT), using single-photon emission computed tomography (performed on a brain-dedicated system) fused with individual magnetic resonance imaging (MRI) scans of the brain. The hypothalamus (representing specific SERT binding) and cerebellum (representing nonspecific binding) were manually delineated on each MRI to assess [123I]FP-CIT binding and specific-to-nonspecific binding ratios.ResultsIn each healthy subject, [123I]FP-CIT binding was higher in the hypothalamus than in the cerebellum, and the mean hypothalamic binding ratio of SERT was 0.29 ± 0.23. We found no difference in hypothalamic binding ratios between HI, PI, and control subjects (HI 0.16 ± 0.24, PI 0.45 ± 0.39, C 0.29 ± 0.23, p value 0.281).ConclusionsWe were able to demonstrate SERT binding in the human hypothalamus in vivo. However, we did not find altered hypothalamic SERT binding in patients with hypothalamic impairment.Trial registrationNetherlands Trial Register: NTR2520

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Serotonin transporter binding in the hypothalamus correlates negatively with tonic heat pain ratings in healthy subjects: A [11C]DASB PET study

Cited by 29 publications

References 61 publications

Occupancy of serotonin transporter by tramadol: a positron emission tomography study with [11C]DASB

Occupancy of serotonin transporter by tramadol: a positron emission tomography study with [11C]DASB

Serotonin and molecular neuroimaging in humans using PET

Imaging of serotonin transporters with [123I]FP-CIT SPECT in the human hypothalamus

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