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Neuron Jul 2023Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many...
Vagal sensory neurons monitor mechanical and chemical stimuli in the gastrointestinal tract. Major efforts are underway to assign physiological functions to the many distinct subtypes of vagal sensory neurons. Here, we use genetically guided anatomical tracing, optogenetics, and electrophysiology to identify and characterize vagal sensory neuron subtypes expressing Prox2 and Runx3 in mice. We show that three of these neuronal subtypes innervate the esophagus and stomach in regionalized patterns, where they form intraganglionic laminar endings. Electrophysiological analysis revealed that they are low-threshold mechanoreceptors but possess different adaptation properties. Lastly, genetic ablation of Prox2 and Runx3 neurons demonstrated their essential roles for esophageal peristalsis in freely behaving mice. Our work defines the identity and function of the vagal neurons that provide mechanosensory feedback from the esophagus to the brain and could lead to better understanding and treatment of esophageal motility disorders.
Topics: Animals; Mice; Core Binding Factor Alpha 3 Subunit; Esophagus; Gastrointestinal Motility; Homeodomain Proteins; Mechanoreceptors; Neurons, Afferent; Sensory Receptor Cells; Stomach; Vagus Nerve
PubMed: 37192624
DOI: 10.1016/j.neuron.2023.04.025 -
Cell Mar 2024Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG...
Dorsal root ganglia (DRG) somatosensory neurons detect mechanical, thermal, and chemical stimuli acting on the body. Achieving a holistic view of how different DRG neuron subtypes relay neural signals from the periphery to the CNS has been challenging with existing tools. Here, we develop and curate a mouse genetic toolkit that allows for interrogating the properties and functions of distinct cutaneous targeting DRG neuron subtypes. These tools have enabled a broad morphological analysis, which revealed distinct cutaneous axon arborization areas and branching patterns of the transcriptionally distinct DRG neuron subtypes. Moreover, in vivo physiological analysis revealed that each subtype has a distinct threshold and range of responses to mechanical and/or thermal stimuli. These findings support a model in which morphologically and physiologically distinct cutaneous DRG sensory neuron subtypes tile mechanical and thermal stimulus space to collectively encode a wide range of natural stimuli.
Topics: Animals; Mice; Ganglia, Spinal; Sensory Receptor Cells; Single-Cell Gene Expression Analysis; Skin
PubMed: 38442711
DOI: 10.1016/j.cell.2024.02.006 -
Cell Aug 2023The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology...
The properties of dorsal root ganglia (DRG) neurons that innervate the distal colon are poorly defined, hindering our understanding of their roles in normal physiology and gastrointestinal (GI) disease. Here, we report genetically defined subsets of colon-innervating DRG neurons with diverse morphologic and physiologic properties. Four colon-innervating DRG neuron populations are mechanosensitive and exhibit distinct force thresholds to colon distension. The highest threshold population, selectively labeled using Bmpr1b genetic tools, is necessary and sufficient for behavioral responses to high colon distension, which is partly mediated by the mechanosensory ion channel Piezo2. This Aδ-HTMR population mediates behavioral over-reactivity to colon distension caused by inflammation in a model of inflammatory bowel disease. Thus, like cutaneous DRG mechanoreceptor populations, colon-innervating mechanoreceptors exhibit distinct anatomical and physiological properties and tile force threshold space, and genetically defined colon-innervating HTMRs mediate pathophysiological responses to colon distension, revealing a target population for therapeutic intervention.
Topics: Ganglia, Spinal; Mechanoreceptors; Colon; Neurons; Skin
PubMed: 37541195
DOI: 10.1016/j.cell.2023.07.007 -
Neuron Jun 2023Light touch sensation begins with activation of low-threshold mechanoreceptor (LTMR) endings in the skin and propagation of their signals to the spinal cord and...
Light touch sensation begins with activation of low-threshold mechanoreceptor (LTMR) endings in the skin and propagation of their signals to the spinal cord and brainstem. We found that the clustered protocadherin gamma (Pcdhg) gene locus, which encodes 22 cell-surface homophilic binding proteins, is required in somatosensory neurons for normal behavioral reactivity to a range of tactile stimuli. Developmentally, distinct Pcdhg isoforms mediate LTMR synapse formation through neuron-neuron interactions and peripheral axonal branching through neuron-glia interactions. The Pcdhgc3 isoform mediates homophilic interactions between sensory axons and spinal cord neurons to promote synapse formation in vivo and is sufficient to induce postsynaptic specializations in vitro. Moreover, loss of Pcdhgs and somatosensory synaptic inputs to the dorsal horn leads to fewer corticospinal synapses on dorsal horn neurons. These findings reveal essential roles for Pcdhg isoform diversity in somatosensory neuron synapse formation, peripheral axonal branching, and stepwise assembly of central mechanosensory circuitry.
Topics: Sensory Receptor Cells; Spinal Cord; Cadherins; Synapses; Spinal Cord Dorsal Horn; Protein Isoforms
PubMed: 37028432
DOI: 10.1016/j.neuron.2023.03.012 -
BMC Musculoskeletal Disorders Jun 2023The purpose of this study was to investigate the effect of instrument-assisted soft tissue mobilization (IASTM) versus myofascial release therapy (MRT) on college... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The purpose of this study was to investigate the effect of instrument-assisted soft tissue mobilization (IASTM) versus myofascial release therapy (MRT) on college students with chronic mechanical neck pain (CMNP).
METHODS
Thirty-three college students with a mean age of 21.33 ± 0.98 involved in distance learning due to the Corona Virus 2019 (COVID-19) restriction were randomized to receive either IASTM on the upper trapezius and levator scapulae muscles or MRT. Researchers measured their pain with a visual analog scale (VAS), function with neck disability index (NDI), and pain pressure threshold (PPT) with a pressure algometer. The subjects received eight therapy sessions over four weeks and outcome measures were assessed pre and post-intervention. The study was registered as a clinical trial on clinicaltrials.gov (registration number: NCT05213871).
RESULT
Unpaired t-test showed no statistical significance between the two groups post-intervention regarding improvement in pain, function, and PPT (p > 0.05).
CONCLUSION
This study showed insignificant differences between groups. However, we did not use a control group, indicating that the improvement in outcomes may not have been caused by the intervention.
STUDY DESIGN
Quasi-experimental two groups pre-posttest clinical trial.
LEVEL OF EVIDENCE
Therapy, level 2b.
Topics: Humans; Young Adult; Adult; Neck Pain; Myofascial Release Therapy; COVID-19; Pain Threshold; Myofascial Pain Syndromes; Chronic Pain
PubMed: 37270471
DOI: 10.1186/s12891-023-06540-5 -
Trials Jun 2023Muscle stretching exercises preserve corporal flexibility and decrease the retraction and shortening of myofascial and articular structures. These exercises are... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Muscle stretching exercises preserve corporal flexibility and decrease the retraction and shortening of myofascial and articular structures. These exercises are recommended for the treatment of fibromyalgia (FM). The purpose of the study was to verify and compare the effect of muscle stretching exercises on FM patients based on the global posture reeducation method against segmental muscle stretching exercises, both used in concert with an educational approach rooted in cognitive behavioral therapy.
METHODS
Forty adults with FM were randomly allocated into two groups: global and segmental. The two kinds of therapies were performed in 10 individual sessions once a week. Two assessments were made: one at baseline and one at the end of therapy. The primary outcome variable was pain intensity (Visual Analog Scale). The secondary outcome variables were multidimensional pain (McGill Pain Questionnaire), the pain threshold at tender points (dolorimetry), attitudes toward chronic pain (Survey of Pain Attitudes-Brief Version), body posture (Postural Assessment Software Protocol), postural control (Modified Clinical Test of Sensory Interaction on Balance), flexibility (sit-and-reach test), the impact of FM on quality of life (Fibromyalgia Impact Questionnaire, FIQ), and self-reported perceptions and body self-care.
RESULTS
At the end of treatment, there were no statistically significant differences between the groups in the outcome variables. Furthermore, the groups presented lower pain intensity (baseline vs. final; global group: 6 ± 1.8 vs. 2.2 ± 1.6 cm, p<0.01; segmental group: 6.3 ± 2.1 vs. 2.5 ± 1.7 cm, p<0.01), higher pain threshold (p ≤ 0.01), lower total FIQ score (p < 0.01), and greater postural control (p < 0.01) after treatment.
CONCLUSIONS
Muscle stretching exercises based on global posture reeducation and segmental muscle stretching exercises, both used in concert with an educational approach rooted in cognitive behavioral therapy, reduced the pain intensity and impact of FM on quality of life. These exercises also improved FM patients' pain threshold at tender points, attitudes toward chronic pain, and postural control. There were no differences between global posture reeducation and segmental muscle stretching exercises.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02384603 . Registered on 10 March 2015.
Topics: Adult; Humans; Fibromyalgia; Muscle Stretching Exercises; Quality of Life; Chronic Pain; Posture; Treatment Outcome
PubMed: 37280637
DOI: 10.1186/s13063-023-07422-w