bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.64898/2026.10.08.757642

Precision cell-state silencing of injured afferents alleviates spontaneous neuropathic pain

Cooper, A. H.·Chrysostomidou, P.·Jurado Santos, A.·Cui, H.·Adesida, S.·Redondo Canales, M.·Bakina, A.·Barry, A. M.·Baskozos, G.·Bennett, D. L.·Weir, G. A.
View original source ↗Export metadata ↓

Abstract

Excessive primary afferent activity sustains neuropathic pain, but safe and effective therapeutic inhibition has proved elusive. Realising the promise of gene therapies to meet this challenge requires strategies to identify and selectively target the neuronal populations responsible. Here, we use chemo- and optogenetic approaches to demonstrate that activity in injured afferents drives spontaneous pain but is dispensable for normal sensory function, thereby creating a therapeutic opportunity. Guided by chromatin accessibility profiling, we create an injury-responsive viral vector that confers >95% specificity for injured sensory neurons. Combined with the translationally relevant chemogenetic PSAM4-GlyR, this targeting module effectively silences hyperexcitable human sensory neurons and alleviates spontaneous neuropathic pain in mice. These findings establish precision cell-state targeting of sensory neurons as a promising therapeutic strategy for chronic pain.

Explore related subjects

neurosciencePreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Cooper, A. H., Chrysostomidou, P., Jurado Santos, A., Cui, H., Adesida, S., Redondo Canales, M., Bakina, A., Barry, A. M., Baskozos, G., Bennett, D. L., Weir, G. A.. 2026-10-15. Precision cell-state silencing of injured afferents alleviates spontaneous neuropathic pain. https://doi.org/10.64898/2026.10.08.757642

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

B-REAL: A keypoint-less behavior platform for offline classification and real-time detection

Two obstacles limit automated behavior analysis in neuroethology: the burden of first training pose estimation models, and the inability to identify behavior quickly enough for real-time classification that could trigger stimuli, drug delivery, or environmental manipulations. Here we present B-REAL, a pose-free classifier that maps raw video to behavior faster than video frames are recorded, even on a CPU. Given substantially less training data, B-REAL matched or surpassed established methods trained on full benchmark rodent or fly datasets, particularly on rare and even single-frame behaviors. Pretraining on unlabeled video further improves its accuracy without slowing inference or training time. In closed loop, rewarding mice for B-REAL-detected grooming more than doubled their performance of grooming bouts. B-REAL thus makes closed-loop behavioral experiments practical with minimal annotation and standard hardware.

neuroscience↗
bioRxiv2026

Comparing re-referencing methods for human intracranial EEG

Stereo-electroencephalography (SEEG) involves the implantation of depth electrodes in the brain to monitor epileptic seizures for surgical feasibility. As the electrodes advance into deeper limbic structures, the macro contacts distributed along the shaft record electrical activity from more lateral sites, while a bundled array of microwires simultaneously captures highly localised signals from the tip of the electrode. In a clinical setting these electrical signals are recorded relative to a reference signal, which may be sub-optimal for subsequent analyses that are unrelated to clinical objectives. Therefore, a secondary re-referencing operation is often undertaken to transform the signal in relation to a specific hypothesis. Despite a recent surge in SEEG studies, comparative studies on the much-understudied issue of re-referencing are sparse. Here, we analyse data collected from 16 human patients during an episodic memory task and comparatively apply a range of re-referencing methods to both macro contact and micro-wire data. We find that the choice of method changes the proportion of trials that survive artefact rejection, low frequency power, and the aperiodic background against which that power is read. In the hippocampal recordings, however, no method differed from any other in the size of a memory effect in power or spike-field coherence. This early transformative decision therefore bears on how the signal is described. We found no evidence that it changes the detectability of the behavioural effects tested here, and no method reversed the direction of a memory effect.

neuroscience↗
bioRxiv2026

Dietary vitamin B5 positively regulates intestinal neuropeptide secretion in C. elegans

Vitamin B5 is an essential vitamin that must be acquired via diet or by the gut microbiota, and vitamin B5 deficiency or altered vitamin B5 metabolism leads to a variety of physiological and neuronal disorders. We conducted a genetic analysis of the effects of exogenous vitamin B5 in C. elegans, and we found that vitamin B5 confers protection to toxicity caused by oxidative stress and acute exposure to vitamin B5 positively regulates neuropeptide secretion. We identified a sodium-dependent multivitamin transporter family member, smvt-1 that is required for B5 uptake into cells and for protection conferred by vitamin B5. Vitamin B5 positively regulates the intestinal secretion of FLP-2, a neuropeptide-like protein whose release activates the antioxidant response. Vitamin B5 promotes FLP-2 secretion rapidly, specifically, and in a manner that is dependent upon uptake into intestinal cells by smvt-1. Vitamin B5-induced neuropeptide secretion is strictly dependent upon the SNARE protein aex-4/SNAP-25 and on the calcium dependent protein kinase C family member, pkc-2/PKCa in the intestine. These results reveal a previously uncharacterized function for dietary vitamin B5 in positively regulating intestinal neuropeptide secretion from dense core vesicles and in shaping the antioxidant response.

neuroscience↗