Biology subjects

Emrick, J. J.

Publications and source records attributed to Emrick, J. J..

5 recordsLinked to original sources

bioRxiv2026

Deep-tissue mechanosensation emerges from the interaction of external force and internal tissue state

Muscle sensation is often considered in terms of proprioception, but muscle pain illustrates that other types of sensory neurons are also involved. Here, we show that trigeminal neurons innervating the masseter muscle fall into three classes: A{beta} low-threshold mechanoreceptors, A{delta} high-threshold mechanoreceptors (A{delta}-HTMRs), and peptidergic neurons (PEP). All three types are recruited by mechanical stimulation, with massage being a particularly effective stimulus. Chemogenetic activation of masseter A{delta}-HTMRs and PEP neurons results in pain-like symptoms. Moreover, acute and chronic inflammation sensitize nociceptors, altering behavioral tolerance in an animal model of massage. Taken together, our results provide a framework for understanding muscle somatosensation and how massage of sore muscles may be painful yet beneficial. SignificanceMuscle sensation is usually most prominent when something goes wrong: after overuse, injury, or inflammation, even ordinary pressure or movement can become painful. Yet how mechanical force is detected in muscle, and when a stimulus becomes painful, remain poorly understood. Here, we identify a simple cellular organization for muscle mechanosensation in which three sensory-neuron classes encode force through graded population recruitment. Massage effectively recruited all three classes, including the two nociceptive populations. We further show that these nociceptive neurons are sensitized by acute and chronic inflammation, leading to enhanced recruitment during massage. These findings show that the representation of mechanical force in muscle can be shaped by tissue state and provide a foundation for understanding muscle soreness, pain, and therapeutic touch.

neuroscience↗

bioRxiv2026

Trpv1+ sensory innervation of the salivary gland drives pain and supports saliva secretion

Sensory neurons have been increasingly recognized as vital contributors to deep tissue function. However, how these specialized neurons contribute to salivary gland function remains largely undefined. Here, we uncover a role for trigeminal somatosensory afferents in salivary gland perception and function using in situ-based classification, in vivo calcium imaging, behavioral assays, and targeted ablation. Retrograde labeling from the submandibular gland complex revealed substantial direct innervation from trigeminal neurons. Further categorization confirmed that Trpv1+ sensory neurons provided dense innervation of the Whartons ducts. TRPV1 agonist ductal infusion directly activated gland complex-associated neurons in the trigeminal ganglia and evoked a robust pain phenotype. Targeted Trpv1+ ablation disrupted Whartons ducts structure and dramatically reduced stimulated saliva volume. Our work provides the first evidence that Trpv1+ sensory neurons maintain salivary architecture and are necessary for stimulated saliva production, revealing a vital interoceptive role for direct trigeminal innervation in submandibular gland health.

physiology↗

bioRxiv2026

LabGrymace: Automated Analysis of Mouse Grimace for Quantitative Assessment of Pain Dynamics

Accurate assessment of pain in animal models is essential for understanding pain mechanisms, developing analgesics, and ensuring animal welfare. The Mouse Grimace Scale (MGS) provides a sensitive, non-invasive measure of spontaneous pain by quantifying pain-related facial expressions, but its utility is limited by labor-intensive manual scoring, observer variability, and reliance on static images that fail to capture the temporal dynamics of facial behavior. Existing automated approaches improve throughput but typically rely on highly standardized imaging conditions, selected viewing angles, and static facial appearance, while providing limited temporal resolution and little insight into the relative contributions of individual facial action units. Here, we introduce LabGrymace, an open-source, artificial intelligence-powered framework for automated, frame-by-frame analysis of pain-related facial dynamics in freely moving mice. Built on the LabGym behavioral analysis platform, LabGrymace uses deep-learning-based facial feature detection and tracking to quantify ear, eye, and nose movements continuously from video recordings. To generate a quantitative pain metric and facilitate reproducibility, we calibrated facial dynamics against graded chemogenetic activation of nociceptors and identified the kinematic features most strongly associated with pain intensity. These features were integrated into a weighted composite pain score that reflects the differential contributions of individual facial action units. LabGrymace accurately classified pain-related facial actions and generated continuous pain scores without manual frame selection or restrictive recording conditions. The resulting pain scale exhibited dose-dependent responses generalized across distinct pain modalities, including visceral pain induced by MgSO and somatic pain induced by capsaicin. By combining automated facial-feature analysis with quantitative temporal modeling, LabGrymace provides an objective, scalable, interpretable, and flexible tool for assessing spontaneous pain in laboratory mice.

neuroscience↗

bioRxiv2025

KneEZ Clear, an Effective Tissue Clearing Protocol to Study Musculoskeletal Tissues in the Mouse

Wholemount, 3-dimensional (3D) tissue imaging holds significant promise for analyzing heterogeneous musculoskeletal tissues, such as knee joints, that demand time- and labor-intensive processing using traditional histological methods. Current musculoskeletal clearing protocols rely on either solvent-based tissue clearing, which substantially alters the size and architecture of cleared tissues, possibly compromising downstream quantification and perhaps more importantly reducing signal from endogenous fluorescent reporters, or on expensive and time-consuming hydrogel-based approaches that requires specialized equipment. While aqueous-based clearing overcomes these challenges, there is a clear need for a method that is optimized for clearing musculoskeletal tissues and that can easily be implemented in a standard lab environment. Here, we present KneEZ Clear, a simple, rapid, and flexible aqueous-based method that renders mineralized and non-mineralized tissues of murine knee joints optically transparent. We show that KneEZ Clear, which is based on the EZ Clear method, is highly flexible, demonstrating efficacy in a wide range of murine musculoskeletal tissues including the vertebral column, hindlimb, skull, and teeth. Critically, KneEZ Clear does not require specialized equipment and retains endogenous signal from fluorophores and fluorescent proteins. Additionally, following clearing and wholemount imaging, precious samples can still be processed for subsequent 2D histological analyses for validation or further study. Finally, we show that KneEZ Clear can be applied to samples of disease models to reveal alterations in tissue architecture and homeostasis. The simplicity, versatility, and efficiency of KneEZ Clear for optical clearing of musculoskeletal tissues will accelerate our understanding of cellular interactions and dynamics in homeostasis and disease.

physiology↗

bioRxiv2024

Intradental mechano-nociceptors serve as sentinels that prevent tooth damage

Pain is the anticipated output of the trigeminal sensory neurons that innervate the tooths vital interior1,2; however, the contribution of intradental neurons to healthy tooth sensation has yet to be defined. Here, we employ in vivo Ca2+ imaging to identify and define a population of myelinated high-threshold mechano-nociceptors (intradental HTMRs) that detect superficial structural damage of the tooth, produce pain, and initiate a jaw opening reflex. Intradental HTMRs remain inactive when direct forces are applied to the intact tooth but become responsive to forces when the structural integrity of the tooth is compromised, and the dentin or pulp is exposed. Their terminals collectively innervate the inner dentin through overlapping receptive fields, allowing them to monitor the superficial structures of the tooth. Indeed, intradental HTMRs detect superficial enamel damage and encode its degree, and their responses persist in the absence of either PIEZO2 or Nav1.83,4. As predicted, chemogenetic activation of intradental HTMRs results in a marked pain phenotype like that produced by systemic chemogenetic activation of nociceptors. Remarkably, optogenetic activation of intradental HTMRs triggers a rapid, jaw opening reflex via contraction of the digastric muscle. Taken together, our data indicate that intradental HTMRs serve as sentinels that guard against mechanical threats to the tooth; their activation not only triggers pain, but also results in physical tooth separation, which would prevent damage during mastication. Our work provides a new perspective of intradental neurons, highlighting their protective role, and illustrates the functional diversity of interoreceptors.

neuroscience↗