Biology subjects

Tinnermann, A.

Publications and source records attributed to Tinnermann, A..

5 recordsLinked to original sources

bioRxiv2026

Starting strong: A descending analgesic dosing scheme enhances pain relief compared to a conventional ascending dosing scheme

Managing pain while minimizing opioid-related harm remains a central clinical challenge. Enhancing drug-related placebo effects has been proposed as one strategy for reducing opioid consumption, yet current dosing guidelines which recommend starting analgesic treatment at a low dose and titrating upward may inadvertently generate negative treatment expectations, since initial drug encounters are often associated with minimal pain relief. This study tested whether the inverse approach of a descending dosing scheme that starts with a strong analgesic dose more effectively enhances placebo-related analgesia than the conventional ascending scheme. Eighty-two healthy participants underwent a heat pain paradigm involving a sham analgesic treatment delivered at three different efficacy levels (low, medium, high). Participants were randomly assigned to a descending (high-to-low) or ascending (low-to-high) treatment-history sequence before receiving an identical, medium-intensity treatment during a subsequent test phase. The descending group showed significantly greater pain relief during the test phase than the ascending group, despite receiving identical treatment. These findings suggest that initiating analgesic treatment with a high, effective dose can amplify placebo-related analgesia relative to conventional dosing schemes, offering a potential strategy for reducing cumulative opioid use without compromising pain relief.

neuroscience↗

bioRxiv2026

Conditioned pain modulation recruits the descending pain modulatory system to inhibit spinal activity

Conditioned pain modulation (CPM) is a phenomenon where the perception of pain is reduced in the presence of a second painful stimulus. In rodents, a similar phenomenon involves descending control pathways that rely on the brainstem to modulate spinal cord activity while in humans, descending mechanisms including the spinal cord remain elusive. In this study, we applied functional MRI to simultaneously record brain and spinal cord responses during CPM in healthy participants. CPM developed over time and was associated with reduced activity in key pain-related brain regions and the spinal cord dorsal horn. Conversely, regions involved in descending pain modulation showed increased activity during CPM. Functional connectivity analyses revealed reduced coupling during CPM between spinal and descending control regions. Our findings demonstrate that CPM involves both the descending pain control system to inhibit spinal activity and bottom-up pain signalling of attenuated spinal responses.

neuroscience↗

bioRxiv2025

EPISeg: Automated segmentation of the spinal cord on echo planar images using open-access multi-center data

Functional magnetic resonance imaging (fMRI) of the spinal cord is relevant for studying sensation, movement, and autonomic function. Preprocessing of spinal cord fMRI data involves segmentation of the spinal cord on gradient-echo echo planar imaging (EPI) images. Current automated segmentation methods do not work well on these data, due to the low spatial resolution, susceptibility artifacts causing distortions and signal drop-out, ghosting, and motion-related artifacts. Consequently, this segmentation task demands a considerable amount of manual effort which takes time and is prone to user bias. In this work, we (i) gathered a multi-center dataset of spinal cord gradient-echo EPI with ground-truth segmentations and shared it on OpenNeuro https://openneuro.org/datasets/ds005143/versions/1.3.0, and (ii) developed a deep learning-based model, EPISeg, for the automatic segmentation of the spinal cord on gradient-echo EPI data. We observe a significant improvement in terms of segmentation quality compared to other available spinal cord segmentation models. Our model is resilient to different acquisition protocols as well as commonly observed artifacts in fMRI data. The training code is available at https://github.com/sct-pipeline/fmri-segmentation/, and the model has been integrated into the Spinal Cord Toolbox as a command-line tool.

neuroscience↗

bioRxiv2023

Ventral premotor cortex influences spinal cord activation during force generation

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is influenced by cerebral primary motor and premotor areas is poorly understood. Here we conducted combined cortico-spinal functional MRI during a simple visually guided isometric force generation task in a group of 20 healthy young subjects. Activation was localized in the ipsilateral cervical spinal cord and contralateral primary motor and premotor areas. The main finding is that spinal activation was influenced by ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding which extends our understanding about human motor function beyond the animal literature.

neuroscience↗

bioRxiv2021

The role of network interactions in opioid analgesia

Opioids are potent analgesic drugs with widespread cortical, subcortical and spinal targets. In particular, the central pain system comprising ascending and descending pain pathways has high opioid receptor densities and is thus crucial for opioid analgesia. Here, we investigated effects of the opioid remifentanil in a large sample (n=78) of healthy male participants using combined cortico-spinal fMRI. This approach offers the possibility to measure BOLD responses simultaneously in the brain and spinal cord allowing us to investigate the role of cortico-spinal coupling in opioid analgesia. Our data show that opioids altered activity in regions involved in pain processing such as somatosensory regions including the spinal cord and pain modulation such as prefrontal regions. Moreover, coupling strength along the descending pain system, i.e. between the medial prefrontal cortex, periaqueductal gray and spinal cord was stronger in participants who reported stronger analgesia during opioid treatment while the reversed pattern was observed in the control group. These results indicate that coupling along the descending pain pathway is a potential mechanism of opioid analgesia and can differentiate between opioid analgesia and unspecific reductions in pain such as habituation.

neuroscience↗