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Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

ABSTRACT: The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45, 47, and 48.9°C) in 38 healthy men (age: 27.05?±?5.7?years). We also reconstructed the MFB using multitensor tractography from diffusion magnetic resonance imaging (dMRI) and calculated free-water corrected dMRI measures of fractional anisotropy (FA_t ), radial diffusivity (RD_t ), and axial diffusivity (AD_t ). Lower ratings of interindividual pain intensity correlated with higher FA_t and lower RD_t of the MFB. As changes in FA_t and RD_t may reflect abnormalities in myelination, the results might be interpreted as that a lower pain rating is associated with higher degree of myelination of the MFB and could represent an inhibitory pathway of pain. Our results suggest that alteration of microstructure in the MFB contributes to the interindividual variation of pain perception.

SUBMITTER: Geisler M

PROVIDER: S-EPMC7856635 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

Geisler Maria M Rizzoni Elizabeth E Makris Nikolaos N Pasternak Ofer O Rathi Yogesh Y Bouix Sylvain S Herbsleb Marco M Bär Karl-Jürgen KJ Weiss Thomas T Kikinis Zora Z

Human brain mapping 20201110 4

The perception of pain to noxious stimuli, also known as pain sensitivity, varies among individuals. The comprised brain structures and their white matter pathways are complex and elusive. Here, we aimed to investigate whether variation of microstructure of the medial forebrain bundle (MFB), a tract connecting the basal forebrain with the brain stem, is associated with interindividual pain sensitivity. We assessed interindividual pain sensitivity as a rating of pain intensity to heat stimuli (45 ...[more]

PMID: 33170528

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Project description:Short- and long-term antidepressant effects of deep brain stimulation (DBS) in treatment-resistant depression (TRD) have been demonstrated for several brain targets in open-label studies. For two stimulation targets, pivotal randomized trials have been conducted; both failed a futility analysis. We assessed efficacy and safety of DBS of the supero-lateral branch of the medial forebrain bundle (slMFB) in a small Phase I clinical study with a randomized-controlled onset of stimulation in order to obtain data for the planning of a large RCT. Sixteen patients suffering from TRD received DBS of the slMFB and were randomized to sham or real stimulation for the duration of 2 months after implantation. Primary outcome measure was mean reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) during 12 months of DBS (timeline analysis). Secondary outcomes were the difference in several clinical measures between sham and real stimulation at 8 weeks and during stimulation phases. MADRS ratings decreased significantly from 29.6 (SD +/- 4) at baseline to 12.9 (SD +/- 9) during 12 months of DBS (mean MADRS, n = 16). All patients reached the response criterion, most patients (n = 10) responded within a week; 50% of patients were classified as remitters after 1 year of stimulation. The most frequent side effect was transient strabismus. Both groups (active/sham) demonstrated an antidepressant micro-lesioning effect but patients had an additional antidepressant effect after initiation of stimulation. Both rapid onset and stability of the antidepressant effects of slMFB-DBS were demonstrated as in our previous pilot study. Given recent experiences from pivotal trials in DBS for MDD, we believe that slow, careful, and adaptive study development is germane. After our exploratory study and a large-scale study, we conducted this gateway trial in order to better inform planning of the latter. Important aspects for the planning of RCTs in the field of DBS for severe and chronic diseases are discussed including meaningful phases of intra-individual and between-group comparisons and timeline instead of single endpoint analyses.

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Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

Publications

Microstructural alterations in medial forebrain bundle are associated with interindividual pain sensitivity.

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