Biology subjects

Malapert, P.

Publications and source records attributed to Malapert, P..

3 recordsLinked to original sources

bioRxiv2025

C-LTMRs Regulate Thermosensation and Gate the Transition from Acute to Chronic Pain

C-low threshold mechanoreceptors (C-LTMRs) are traditionally associated with affective touch, yet emerging evidence suggests broader roles in sensory processing and pain modulation. We developed an intersectional genetic approach to selectively ablate C-LTMRs in adult mice by combining Nav1.8IRES-FLPo and THCreER drivers with a conditional DTR reporter. This approach yields robust, tissue-specific deletion of C-LTMRs without off-target effects in non-sensory tissues. C-LTMR-ablated mice exhibit altered thermotaxis behavior, including a sharpened and spatially restricted preference for warmth, while maintaining largely intact responses to touch. Remarkably, following surgical or chemotherapeutic injury, these mice display persistent mechanical and cold hypersensitivity, implicating C-LTMRs in the resolution of pain. Transcriptomic profiling of dorsal root ganglia (DRG) and dorsal horn of the spinal cord (DHSC) revealed widespread transcriptional dysregulation in pathways related to extracellular matrix remodeling, vascular function and gliogenesis in naive mice. In C-LTMR-ablated mice, paclitaxel failed to induce pro-recovery transcriptional programs and instead promoted persistent neuroinflammatory signatures. These findings establish C-LTMRs as key modulators of pain recovery, acting through tissue-specific transcriptional programs that suppress inflammation and support sensory homeostasis.

neuroscience↗

bioRxiv2024

Single cell RNA-sequencing reveals GINIP-expressing neurons as the main targets of focused ultrasound

Dorsal root ganglion (DRG) neurons have a wide range of functions, including touch, pain and itch. These neurons have emerged as promising targets for non-invasive focused ultrasound (FUS) neuromodulation. However, our knowledge of the molecular and physical mechanisms underlying FUS-evoked responses in DRG neurons is limited. Here, we investigate the neuromodulatory capabilities of FUS in cultured DRG neurons in combination with calcium imaging. We find that a 20-MHz FUS burst of 1-ms duration at an acoustic pressure of 5 MPa elicited calcium responses in 52% of DRG neurons. Single-cell RNA sequencing reveals that the majority of FUS-sensitive neurons belong to three subsets of DRG neurons; C-LTMRs, the MRGPRD-expressing C-HTMRs and A6-LTMRs. FUS excites all these neuronal subtypes by membrane deformation, suggesting a mechanism mediated by mechanosensitive ion channels. Our results identify FUS parameters that activate distinct subsets of DRG neurons and open new avenues for using FUS stimulation to modulate DRG neuron function.

neuroscience↗

bioRxiv2023

Gut microbiota promotes pain chronicity in Myosin1A deficient male mice

Over the past decade, the gut microbiota has emerged as an important regulator of nervous systems health and disease states1. Yet, its contribution to the pathogenesis of chronic somatic pain remains poorly documented. Chronic pain is a heavily debilitating disease affecting more than 1.5 billion people worldwide that can manifest through a long-lasting hypersensitivity to mechanical and/or thermal stimulations2,3. Maladaptive responses of dorsal root ganglia (DRG) neurons and spinal cord (SC) interneurons to tissue injuries and also of non-neuronal cells including DRG macrophages and SC microglia are acknowledged as important drivers of sensory symptoms underlying chronic pain4,3,5-7. Recent evidence shows that signals from gut microbiota are required for the initiation of injury-induced sensory hypersensitivity, via the ability to interact with the immune system8-11. However, whether and how gut microbiota promotes pain chronicity remains unknown. Here, we report that male mice lacking Myosin1a (KO)12 raised under single genotype housing conditions (KO-SGH) are predisposed to develop chronic injury-induced mechanical pain. We demonstrate that this predisposition is caused by their dysbiotic gut microbiota, which sustains the immune response in the DRG following neuropathic injury. Parental antibiotic treatment modifies gut microbiota composition and completely rescues the injury-induced chronic pain and associated DRG inflammatory response in male KO-SGH offspring. Together, our data establish a causal relationship between a dysbiotic gut microbiota and the predisposition to injury-induced chronic pain.

neuroscience↗