Chronic pain and itch are a pathological operation of the somatosensory system at the levels of primary sensory neurons, spinal cord and brain. Pain and itch are clearly distinct sensations, and recent studies have revealed the separate neuronal pathways that are involved in each sensation. However, the mechanisms by which these sensations turn into a pathological chronic state are poorly understood. A proposed mechanism underlying chronic pain and itch involves abnormal excitability in dorsal horn neurons in the spinal cord. Furthermore, an increasing body of evidence from models of chronic pain and itch has indicated that synaptic hyperexcitability in the spinal dorsal horn might not be a consequence simply of changes in neurons, but rather of multiple alterations in glial cells. Thus, understanding the key roles of glial cells may provide us with exciting insights into the mechanisms of chronicity of pain and itch, and lead to new targets for treating chronic pain and itch.
Animals ; Chronic Pain ; pathology ; Humans ; Neuralgia ; metabolism ; Pruritus ; pathology ; Sensory Receptor Cells ; physiology ; Spinal Cord ; pathology

Lung cancer is a major medical problem. Despite advances in molecular biology and pharmacology, the outcome of lung cancer treatment is unsatisfactory. Clinically, inflammation and cancer are closely associated, and, genetically, these two processes are regulated by the same gene loci. Inflammation promotes cancer formation. Increasing evidence shows that neuroimmune interaction involving inflammatory disease and the vagus nerves are crucial in the interaction. Airway sensory receptors are biosensors that detect the lung inflammatory process through various mediators and cytokines. This information is transmitted through vagal afferents to the brain and produces a host of responses that regulate the extent and intensity of inflammation. Tumor cells express receptors for neurotransmitters and provide a substrate for direct interaction with neurons. Thus, neural regulation of the immune response is targeted towards inflammation as well as tumors. The airway sensors can detect cancer-related cytokines, which provides a direct pathway to inform the brain of tumor growth. The knowledge of how these sensors may monitor tumor progression and provide neuroimmune interaction in the control of tumor development and metastasis will improve our treatment of lung cancer.
Carcinogenesis ; Cytokines ; physiology ; Humans ; Inflammation ; pathology ; Lung ; innervation ; pathology ; Lung Neoplasms ; pathology ; Sensory Receptor Cells ; physiology ; Vagus Nerve ; physiology

Cough remains the most common reason for patients to seek medical attention. Although the exact prevalence is difficult to estimate, recurrent cough is reported in up to 40% of the population. For the investigation and treatment of chronic cough, it is important to understand its etiology, particularly when the underlying pathology exists outside the respiratory tract. Although there is no consensus as to the best diagnostic strategy for chronic cough, many protocols combine laboratory investigations with empirical trials of treatment. Specific treatment for the underlying disease of cough along with etiologic diagnosis should be emphasized rather than nonspecific antitussive therapy because nonspecific pharmacologic treatments have changed little during the last 50 years, without any significant advances from opiatebased compounds. Recently, molecular structures of cough receptors and mediators have been identified. Vanilloid receptor-1 is one of ion channel receptors expressed on the sensory neurons of cough reflex. Substances inhibiting ion channels and receptor antagonists of tachy-or bradykinins are being investigated. Thus safer and more effective agents to deal with this common problem are believed to be available in the near future.
Bradykinin ; Consensus ; Cough* ; Diagnosis* ; Gastroesophageal Reflux ; Humans ; Ion Channels ; Molecular Structure ; Pathology ; Prevalence ; Reflex ; Respiratory System ; Sensory Receptor Cells

Different physical and chemical stimuli are detected by the peripheral sensory receptors of dorsal root ganglion (DRG) neurons, and the generated inputs are transmitted via afferent fibers into the central nervous system. The gene expression profiles of DRG neurons contribute to the generation, transmission, and regulation of various somatosensory signals. Recently, the single-cell transcriptomes, cell types, and functional annotations of somatosensory neurons have been studied. In this review, we introduce our classification of DRG neurons based on single-cell RNA-sequencing and functional analyses, and discuss the technical approaches. Moreover, studies on the molecular and cellular mechanisms underlying somatic sensations are discussed.
Animals ; Ganglia, Spinal ; cytology ; Gene Regulatory Networks ; Humans ; Pain ; genetics ; metabolism ; pathology ; Sensory Receptor Cells ; metabolism ; Sequence Analysis, RNA ; Transcriptome

Cutaneous neurogenic inflammation (CNI) is inflammation that is induced (or enhanced) in the skin by the release of neuropeptides from sensory nerve endings. Clinical manifestations are mainly sensory and vascular disorders such as pruritus and erythema. Transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) are non-selective cation channels known to specifically participate in pain and CNI. Both TRPV1 and TRPA1 are co-expressed in a large subset of sensory nerves, where they integrate numerous noxious stimuli. It is now clear that the expression of both channels also extends far beyond the sensory nerves in the skin, occuring also in keratinocytes, mast cells, dendritic cells, and endothelial cells. In these non-neuronal cells, TRPV1 and TRPA1 also act as nociceptive sensors and potentiate the inflammatory process. This review discusses the role of TRPV1 and TRPA1 in the modulation of inflammatory genes that leads to or maintains CNI in sensory neurons and non-neuronal skin cells. In addition, this review provides a summary of current research on the intracellular sensitization pathways of both TRP channels by other endogenous inflammatory mediators that promote the self-maintenance of CNI.
Animals ; Chronic Disease ; Dendritic Cells ; metabolism ; pathology ; Dermatitis ; metabolism ; pathology ; Gene Expression Regulation ; Humans ; Inflammation ; metabolism ; pathology ; Keratinocytes ; metabolism ; pathology ; Mast Cells ; metabolism ; pathology ; Sensory Receptor Cells ; metabolism ; pathology ; TRPA1 Cation Channel ; biosynthesis ; TRPV Cation Channels ; biosynthesis

Peripheral itch stimuli are transmitted by sensory neurons to the spinal cord dorsal horn, which then transmits the information to the brain. The molecular and cellular mechanisms within the dorsal horn for itch transmission have only been investigated and identified during the past ten years. This review covers the progress that has been made in identifying the peptide families in sensory neurons and the receptor families in dorsal horn neurons as putative itch transmitters, with a focus on gastrin-releasing peptide (GRP)-GRP receptor signaling. Also discussed are the signaling mechanisms, including opioids, by which various types of itch are transmitted and modulated, as well as the many conflicting results arising from recent studies.
Action Potentials ; drug effects ; Analgesics, Opioid ; pharmacology ; Animals ; Humans ; Pruritus ; metabolism ; pathology ; Sensory Receptor Cells ; metabolism ; Spinal Cord ; pathology ; Synaptic Transmission ; physiology

A subset of patients of amyotrophic lateral sclerosis (ALS) present with mutation of Cu/Zn superoxide dismutase 1 (SOD1), and such mutants caused an ALS-like disorder when expressed in rodents. These findings implicated SOD1 in ALS pathogenesis and made the transgenic animals a widely used ALS model. However, previous studies of these animals have focused largely on motor neuron damage. We report herein that the spinal cords of mice expressing a human SOD1 mutant (hSOD1-G93A), besides showing typical destruction of motor neurons and axons, exhibit significant damage in the sensory system, including Wallerian-like degeneration in axons of dorsal root and dorsal funiculus, and mitochondrial damage in dorsal root ganglia neurons. Thus, hSOD1-G93A mutation causes both motor and sensory neuropathies, and as such the disease developed in the transgenic mice very closely resembles human ALS.
Amyotrophic Lateral Sclerosis/enzymology/*pathology ; Animals ; Axons/*pathology ; Disease Models, Animal ; Ganglia, Spinal/pathology ; Humans ; Mice ; Mice, Transgenic ; Mitochondria/pathology ; Motor Neurons/metabolism/pathology ; Mutation ; Nerve Degeneration/*pathology ; Sensory Receptor Cells/*pathology ; Spinal Cord/*pathology ; Superoxide Dismutase/genetics/*physiology