Biology subjects

Nahman-Averbuch, H.

Publications and source records attributed to Nahman-Averbuch, H..

6 recordsLinked to original sources

bioRxiv2026

Hormonal factors are poor indicators of endometriosis pain

Endometriosis is a common yet understudied condition in which sex hormones play a key role in the etiology and pathophysiology of the disease. Sex hormones are dysregulated in endometriosis and are pharmacologically targeted to reduce symptoms including pain, but the relationships between endometriosis-related pain with sex hormone levels and their receptors are not clear. In 60 women previously diagnosed or undergoing laparoscopic surgery for the diagnosis of endometriosis, we collected patient-reported endometriosis/pelvic pain intensity in the last 30 days, pain interference scale, and the Endometriosis Health Profile 30 (EHP30) pain subscale. In a sub-sample of 38 participants, biopsies from control non-lesion pelvic peritoneum and endometrial lesion tissues were collected during surgery to analyze the tissue abundance of the primary receptors for estrogen, as well as androgen, progesterone, and prolactin receptors. Serum was collected to analyze systemic sex hormone levels including estradiol, prolactin, progesterone, and testosterone. Between tissues, we found elevated transcript levels for estrogen receptor alpha (ESR1) in lesions, but no difference in estrogen receptor beta (ESR2) transcript levels between tissue samples were found. Relating tissue receptor transcript levels to clinical pain revealed that only ESR1 and PGR in lesions were negatively associated with endometriosis/pelvic pain intensity, however, following false discovery rate correction the association with ESR1 was no longer statistically significant. No other tissue or systemic factors were associated with clinical pain outcomes. Together, these data demonstrate unique alterations in receptor abundance in lesions yet select transcript levels only weakly relate to pain in endometriosis.

neuroscience↗

bioRxiv2026

Preferential innervation of endometriosis by hyperexcitable Ret/GFRα1+ nociceptors associates with target GDNF and clinical pain

Endometriosis is a prevalent condition characterized by chronic pelvic pain that is frequently refractory to treatment. While the mechanisms underlying this pain remain poorly defined, clinical evidence often indicates that lesion innervation, but not disease stage (e.g. number and depth of lesions), correlate with pelvic pain severity. However, characterization of lesion-innervating neurons is incomplete, revealing an opportunity to identify novel, disease-modifying therapeutics. Here, we coupled functional analyses of lesion-innervating neurons in a mouse model with concurrent identification and characterization of lesion-innervating neurons from pain-phenotyped endometriosis patients. Following the confirmation of abdominal-directed pain-like behaviors in the mouse model, electrophysiological analysis revealed that lesion-innervating dorsal root ganglion (DRG) neurons are hyperexcitable compared to matched controls. These neurons are predominantly small-diameter and bind Isolectin B4, an established marker of the GDNF Family Ligand receptor, Ret. GDNF is concentrated within the stromal layer of both mouse and human lesions, adjacent to axons expressing the GDNF co-receptor, GFR1. Critically, clinical pain correlates with lesion GDNF level, axonal density, and neuronal GFR1 levels. These data provide evidence that endometrial lesions may recruit the Ret-positive subpopulation of nociceptors where they become sensitized and increase patient pain.

neuroscience↗

bioRxiv2024

The brainstem's red nucleus was evolutionarily upgraded to support goal-directed action

The red nucleus is a large brainstem structure that coordinates limb movement for locomotion in quadrupedal animals (Basile et al., 2021). The humans red nucleus has a different pattern of anatomical connectivity compared to quadrupeds, suggesting a unique purpose (Hatschek, 1907). Previously the function of the human red nucleus remained unclear at least partly due to methodological limitations with brainstem functional neuroimaging (Sclocco et al., 2018). Here, we used our most advanced resting-state functional connectivity (RSFC) based precision functional mapping (PFM) in highly sampled individuals (n = 5) and large group-averaged datasets (combined N [~] 45,000), to precisely examine red nucleus functional connectivity. Notably, red nucleus functional connectivity to motor-effector networks (somatomotor hand, foot, and mouth) was minimal. Instead, red nucleus functional connectivity along the central sulcus was specific to regions of the recently discovered somato-cognitive action network (SCAN; (Gordon et al., 2023)). Outside of primary motor cortex, red nucleus connectivity was strongest to the cingulo-opercular (CON) and salience networks, involved in action/cognitive control (Dosenbach et al., 2007; Newbold et al., 2021) and reward/motivated behavior (Seeley, 2019), respectively. Functional connectivity to these two networks was organized into discrete dorsal-medial and ventral-lateral zones. Red nucleus functional connectivity to the thalamus recapitulated known structural connectivity of the dento-rubral thalamic tract (DRTT) and could prove clinically useful in functionally targeting the ventral intermediate (VIM) nucleus. In total, our results indicate that far from being a motor structure, the red nucleus is better understood as a brainstem nucleus for implementing goal-directed behavior, integrating behavioral valence and action plans.

neuroscience↗

bioRxiv2022

Not all noise-reduction methods for fMRI preprocessing are created equal

Preprocessing fMRI data requires striking a fine balance between conserving signals of interest and removing noise. Typical steps of preprocessing include motion correction, slice timing correction, spatial smoothing, and high-pass filtering. However, these standard steps do not remove many sources of noise. Thus, noise-reduction techniques such as CompCor and FIX have been developed to further improve the ability to draw meaningful conclusions from the data. The ability of these techniques to minimize noise while conserving signals of interest has been tested almost exclusively in resting-state fMRI datasets and, only rarely, in task-related fMRI datasets. Application of noise-reduction techniques to task-related fMRI is particularly important given that such procedures have been shown to reduce false positive rates. However, little remains known about the impact of different noise reduction techniques on the retention of signal, particularly during tasks that may be associated with systemic physiological changes. In this paper, we compared two noise-reduction techniques, i.e. FIX and CompCor, in an fMRI dataset including noxious heat stimulation and non-noxious auditory stimulation. Results show that preprocessing including FIX noise-reduction technique conserves significantly more signal than a preprocessing protocol including CompCor noise-reduction technique in both noxious heat and non-noxious auditory stimulations, while removing only slightly less noise. These results suggest that FIX might be the most appropriate technique to achieve the balance between conserving signals of interest and removing noise.

neuroscience↗

bioRxiv2020

DISSOCIATION BETWEEN INDIVIDUAL DIFFERENCES IN SELF-REPORTED PAIN INTENSITY AND UNDERLYING BRAIN ACTIVATION

Pain is a uniquely individual experience. Previous studies have highlighted changes in brain activation and morphology associated with inter- and intra-individual pain perception. In this study we sought to characterize brain mechanisms associated with individual differences in pain in a large sample of healthy participants (N = 101). Pain ratings varied widely across individuals. Moreover, individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. However, brain activation related to inter-individual differences in pain was not detected, despite clear sensitivity of the BOLD signal to small differences in noxious stimulus intensities within individuals. These findings raise questions about the utility of fMRI as an objective measure to infer reported pain intensity.

neuroscience↗

bioRxiv2020

Pain sensitivity does not differ between obese and healthy weight individuals

There is emerging evidence suggesting a relationship between obesity and chronic pain. We investigated whether pain-free obese individuals display altered pain responses to acute noxious stimuli, thus raising the possibility of greater pain sensitivity and potential susceptibility for chronic pain development. Psychophysical and anthropometric data were collected from 39 individuals with an obese body mass index (BMI) classification (BMI[≥]30) and 40 age/sex-matched individuals of a healthy BMI (BMI<24.9). Since BMI may be an inaccurate index of obesity, additional anthropometric parameters of central adiposity, and percent body fat (BF%) were examined. Pain responses to supra-threshold noxious heat and cold stimuli were examined. Subjects provided pain intensity and unpleasantness ratings to noxious heat (49{degrees}C) applied at varying durations (5s, 12s, 30s) and locations (ventral forearm/lower leg). Cold pain ratings, thresholds, and tolerances were obtained following immersion of the hand in a cold-water bath (0-2{degrees}C). Between-group differences in pain responses, as well as relationships between pain responses and obesity parameters were examined. Importantly, confounds that may influence pain such as anxiety, depression, impulsivity, sleepiness, and quality of life were assessed. No between-group differences in pain sensitivity to noxious heat and cold stimuli were found. After controlling for sex, no relationships were found between BMI, central adiposity, or BF% and pain responses to noxious heat or cold stimuli. These results indicate that obesity, BF%, and central adiposity have little influence on pain sensitivity in obese individuals. Accordingly, it is unlikely that obesity alone increases susceptibility for chronic pain development via amplification of nociceptive processes.

neuroscience↗