Biology subjects

Sprenger, C.

Publications and source records attributed to Sprenger, C..

3 recordsLinked to original sources

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↗

bioRxiv2019

The parietal operculum preferentially encodes heat pain and not salience

Substantial controversy exists as to which part of brain activity is genuinely attributable to pain-related percepts, and which activity is due to general aspects of sensory stimulation, such as its salience, or the accompanying arousal. The challenge posed by this question rests largely in the fact that pain per se exhibits highly intense but unspecific characteristics. These therefore should be matched by potential control conditions. Here, we used a unique combination of functional magnetic resonance imaging, behavioral and autonomic measures to address this longstanding debate in pain research.\n\nSubjects rated perceived intensity in a sequence alternating between heat and sound stimuli. Neuronal activity was monitored using fMRI. Either modality was presented in six different intensities, three of which lay above the pain threshold (for heat) or the unpleasantness threshold (for sound). We performed our analysis on 26 volunteers in which psychophysiological responses (as per skin conductance responses) did not differ between the two stimulus modalities. Having thus ascertained a comparable amount of stimulation-related but unspecific activation, we analyzed stimulus response functions after painful stimulation, and contrasted them with those of the matched acoustic control condition. Furthermore, analysis of fMRI data was performed on the brain surface to circumvent blurring issues stemming from the close proximity of several regions of interest located in heavily folded cortical areas. We focused our analyses on insular and periinsular regions which are strongly involved in processing of painful stimuli. We employed an axiomatic approach to determine areas showing higher activation in painful compared to non-painful heat, and at the same time showing a steeper stimulus response function for painful heat as compared to unpleasant sound. Intriguingly, an area in the posterior parietal operculum emerged whose response showed a pain preference after satisfying all axiomatic constraints.\n\nThis result has important implications for the interpretation of functional imaging findings in pain research, as it clearly demonstrates that there are areas whose activity following painful stimulation is not due to general attributes or results of sensory stimulation, such as salience or arousal. Conversely, several areas did not conform to the formulated axioms to rule out general factors as explanations.

neuroscience↗

bioRxiv2017

Anterior cingulate cortex connectivity is associated with suppression of behavior in a rat model of chronic pain

A cardinal feature of persistent pain that follows injury is a general suppression of behavior, in which motivation is inhibited in a way that promotes energy conservation and recuperation. Across species, the anterior cingulate cortex (ACC) is associated with the motivational aspects of phasic pain, but whether it mediates motivational functions in persistent pain is less clear. Using burrowing behavior as an marker of non-specific motivated behavior in rodents, we studied the suppression of burrowing following painful CFA or control injection into the right knee-joint of 37 rats (18 with pain), and examined associated neural connectivity with ultra-high-field resting state functional MRI. We found that connectivity between ACC and the subcortex correlated with the reduction in burrowing behavior observed following the pain manipulation. In a full replication study we confirmed these findings in a group of 44 rats (23 with pain). Across both datasets, reduced burrowing was assosciated with increased connectivity between ACC and subcortical structures including hypothalamic/preoptic nuclei and the bed nucleus of the stria terminalis. Together, the findings implicate ACC connectivity as a robust correlate of the motivational aspect of persistent pain in rodents.

neuroscience↗