Identification of sensory fiber types in mouse temporomandibular joint tissues.

Temporomandibular joint (TMJ) disorders (TMJDs) are linked to heightened nerve sensitivity in TMJ tissues. To set the groundwork for investigating the mechanisms governing this increased responsiveness, this study aimed to identify the types of nerves in the retrodiscal tissue (retrodisc), anterior disc, and joint capsule of mouse TMJ using immunohistochemistry (IHC) and reporter mice. The pan-sensory neuronal marker pgp9.

Innervation of Retrodiscal Tissues in Patients with Temporomandibular Joint Disorder.

Temporomandibular joint (TMJ) disorders (TMJDs) are a group of musculoskeletal conditions affecting the orofacial region and often associated with facial pain. Understanding the sensory innervation of TMJ structures, particularly the retrodiscal tissue, is essential for identifying pain mechanisms in TMJD because to study these mechanisms, we must first determine the sensory neuronal makeup of the TMJ. However, data on nerve types within TMJ tissues remain limited.

Identification of Sensory Fiber Types in Mouse Temporomandibular Joint Tissues.

Temporomandibular joint (TMJ) disorders (TMJDs) are linked to heightened nerve sensitivity in TMJ tissues. To set the groundwork for investigating the mechanisms governing this increased responsiveness, this study aimed to identify the types of nerves in the retrodiscal tissue (retrodisc), anterior disc, and joint capsule of mouse TMJ using immunohistochemistry (IHC) and reporter mice. The pan-sensory neuronal marker pgp9.

Investigating Mechanically Activated Currents from Trigeminal Neurons of Nonhuman Primates.

Pain sensation often involves mechanical modalities. Mechanically activated (MA) ion channels on sensory neurons underly responsiveness to mechanical stimuli. MA current properties have mainly been derived from rodent sensory neurons.

Modeling Masticatory Myalgia to Headache-like Referred Pain Triggers Local Gene Plasticity at Referred Pain Sites.

Patients with myofascial pain in the head and neck area report widespread and referred pain, including headache. Existing preclinical models fail to replicate this clinical phenotype; therefore, we aimed to develop animal models mimicking referred pain phenomenon and investigate whether referred pain leads to gene plasticity at the referred sites. We modeled masticatory myalgia by stimulation of either the masseter (MM) or temporal muscle (TM) in mice.

Investigating Mechanically Activated Currents from Trigeminal Neurons of Non-Human Primates.

Introduction: Pain sensation has predominantly mechanical modalities in many pain conditions. Mechanically activated (MA) ion channels on sensory neurons underly responsiveness to mechanical stimuli. The study aimed to address gaps in knowledge regarding MA current properties in higher order species such as non-human primates (NHP; common marmosets), and characterization of MA currents in trigeminal (TG) neuronal subtypes.

Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females.

This study investigated the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hindpaws and dorsal root ganglia (DRG). Bulk RNA-seq was used to examine these gene expression changes at 1, 16, and 31 days post-last PTX. At these time points, differentially expressed genes (DEGs) were predominantly related to the reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis.

Degenerative and regenerative peripheral processes are associated with persistent painful chemotherapy-induced neuropathies in males and females.

This study aimed to investigate the time course of gene expression changes during the progression of persistent painful neuropathy caused by paclitaxel (PTX) in male and female mouse hind paws and dorsal root ganglia (DRG). Bulk RNA-seq was used to investigate the gene expression changes in the paw and DRG collected at 1, 16, and 31 days post-PTX. At these time points, differentially expressed DEGs were predominantly related to reduction or increase in epithelial, skin, bone, and muscle development and to angiogenesis, myelination, axonogenesis, and neurogenesis.

Sensory innervation of masseter, temporal and lateral pterygoid muscles in common marmosets.

Myogenous temporomandibular disorders is associated with an increased responsiveness of nerves innervating the masseter (MM), temporal (TM), and lateral pterygoid muscles (LPM). This study aimed to examine sensory nerve types innervating MM, TM and LPM of adult non-human primate-common marmosets. Sensory nerves were localized in specific regions of these muscles.

Associations of tissue damage induced inflammatory plasticity in masseter muscle with the resolution of chronic myalgia.

Gene plasticity during myogenous temporomandibular disorder (TMDM) development is largely unknown. TMDM could be modeled by intramuscular inflammation or tissue damage. To model inflammation induced TMDM we injected complete Freund's adjuvant (CFA) into masseter muscle (MM).

Transcriptional profiles of non-neuronal and immune cells in mouse trigeminal ganglia.

Non-neuronal cells constitute 90%-95% of sensory ganglia. These cells, especially glial and immune cells, play critical roles in the modulation of sensory neurons. This study aimed to identify, profile, and summarize the types of trigeminal ganglion (TG) non-neuronal cells in naïve male mice using published and our own data generated by single-cell RNA sequencing, flow cytometry, and immunohistochemistry.

Transcriptional Profiles of Non-neuronal and Immune Cells in Mouse Trigeminal Ganglia.

Non-neuronal cells constitute 90-95% of sensory ganglia. These cells play critical roles in modulation of nociceptive signal transmissions by sensory neurons. Accordingly, the aim of this review-study was to identify, profile and summarize TG non-neuronal cell types in naïve male mice using published and our own data generated by single-cell RNA sequencing (scRNA-seq), flow cytometry (FC) and immunohistochemistry (IHC).

Association of inflammation and tissue damage induced biological processes in masseter muscle with the resolution of chronic myalgia.

Biological processes linked to intramuscular inflammation during myogenous temporomandibular disorder (TMDM) are largely unknown. We mimicked this inflammation by intra-masseteric muscle (MM) injections of complete Freund’s adjuvant (CFA) or collagenase type 2 (Col), which emulates tissue damage. CFA triggered mechanical hypersensitivity at 1d post-injection was mainly linked to processes controlling chemotactic activity of monocytes and neutrophils.

Trigeminal neurons control immune-bone cell interaction and metabolism in apical periodontitis.

Apical periodontitis (AP) is an inflammatory disease occurring following tooth infection with distinct osteolytic activity. Despite increasing evidence that sensory neurons participate in regulation of non-neuronal cells, their role in the development of AP is largely unknown. We hypothesized that trigeminal ganglia (TG) Nav1.

Sex-dependent pain trajectories induced by prolactin require an inflammatory response for pain resolution.

Pain development and resolution patterns in many diseases are sex-dependent. This study aimed to develop pain models with sex-dependent resolution trajectories, and identify factors linked to resolution of pain in females and males. Using different intra-plantar (i.

A Female-Specific Role for Calcitonin Gene-Related Peptide (CGRP) in Rodent Pain Models.

We aimed to investigate a sexually dimorphic role of calcitonin gene-related peptide (CGRP) in rodent models of pain. Based on findings in migraine where CGRP has a preferential pain-promoting effect in female rodents, we hypothesized that CGRP antagonists and antibodies would attenuate pain sensitization more efficaciously in female than male mice and rats. In hyperalgesic priming induced by activation of interleukin 6 signaling, CGRP receptor antagonists olcegepant and CGRP both given intrathecally, blocked, and reversed hyperalgesic priming only in females.

Prolactin signaling modulates stress-induced behavioral responses in a preclinical mouse model of migraine.

Objective: The aim of this study was to determine if prolactin signaling modulates stress-induced behavioral responses in a preclinical migraine model.

Background: Migraine is one of the most complex and prevalent disorders. The involvement of sex-selective hormones in migraine pathology is highly likely as migraine is more common in women and its frequency correlates with reproductive stages.

Identification of Trigeminal Sensory Neuronal Types Innervating Masseter Muscle.

Understanding masseter muscle (MM) innervation is critical for the study of cell-specific mechanisms of pain induced by temporomandibular disorder (TMDs) or after facial surgery. Here, we identified trigeminal (TG) sensory neuronal subtypes (MM TG neurons) innervating MM fibers, masseteric fascia, tendons, and adjusted tissues. A combination of patch clamp electrophysiology and immunohistochemistry (IHC) on TG neurons back-traced from reporter mouse MM found nine distinct subtypes of MM TG neurons.

Pituitary hormones are specifically expressed in trigeminal sensory neurons and contribute to pain responses in the trigeminal system.

Trigeminal (TG), dorsal root (DRG), and nodose/jugular (NG/JG) ganglia each possess specialized and distinct functions. We used RNA sequencing of two-cycle sorted Pirt-positive neurons to identify genes exclusively expressing in L3-L5 DRG, T10-L1 DRG, NG/JG, and TG mouse ganglion neurons. Transcription factor Phox2b and Efcab6 are specifically expressed in NG/JG while Hoxa7 is exclusively present in both T10-L1 and L3-L5 DRG neurons.

Redefining the Role of Lymphotoxin Beta Receptor in the Maintenance of Lymphoid Organs and Immune Cell Homeostasis in Adulthood.

Lymphotoxin beta receptor (LTβR) is a promising therapeutic target in autoimmune and infectious diseases as well as cancer. Mice with genetic inactivation of LTβR display multiple defects in development and organization of lymphoid organs, mucosal immune responses, IgA production and an autoimmune phenotype. As these defects are imprinted in embryogenesis and neonate stages, the impact of LTβR signaling in adulthood remains unclear.

Meningeal CGRP-Prolactin Interaction Evokes Female-Specific Migraine Behavior.

Objective: Migraine is three times more common in women. CGRP plays a critical role in migraine pathology and causes female-specific behavioral responses upon meningeal application. These effects are likely mediated through interactions of CGRP with signaling systems specific to females.

Sex Differences in Nociceptor Translatomes Contribute to Divergent Prostaglandin Signaling in Male and Female Mice.

Background: There are clinically relevant sex differences in acute and chronic pain mechanisms, but we are only beginning to understand their mechanistic basis. Transcriptome analyses of rodent whole dorsal root ganglion (DRG) have revealed sex differences, mostly in immune cells. We examined the transcriptome and translatome of the mouse DRG with the goal of identifying sex differences.

Transcriptomic sex differences in sensory neuronal populations of mice.

Many chronic pain conditions show sex differences in their epidemiology. This could be attributed to sex-dependent differential expression of genes (DEGs) involved in nociceptive pathways, including sensory neurons. This study aimed to identify sex-dependent DEGs in estrous female versus male sensory neurons, which were prepared by using different approaches and ganglion types.