In 1905, Henry Head first suggested that transmission of pain-related protopathic information can be negatively modulated by inputs from afferents sensing innocuous touch and temperature. In 1965, Melzak and Wall proposed a more concrete gate control theory of pain that highlights the interaction between unmyelinated C fibers and myelinated A fibers in pain transmission. Here we review the current understanding of the spinal microcircuits transmitting and gating mechanical pain or itch. We also discuss how disruption of the gate control could cause pain or itch evoked by innocuous mechanical stimuli, a hallmark symptom for many chronic pain or itch patients.
Animals ; Humans ; Nerve Net ; pathology ; physiopathology ; Pain ; pathology ; Pruritus ; pathology ; Spinal Cord ; pathology ; Synaptic Transmission ; physiology

Pain and itch are unpleasant sensations that often accompany infections caused by viral, bacterial, parasitic, and fungal pathogens. Recent studies show that sensory neurons are able to directly detect pathogens to mediate pain and itch. Nociceptor and pruriceptor neurons respond to pathogen-associated molecular patterns, including Toll-like receptor ligands, N-formyl peptides, and bacterial toxins. Other pathogens are able to silence neuronal activity to produce analgesia during infection. Pain and itch could lead to neuronal modulation of the immune system or behavioral avoidance of future pathogen exposure. Conversely, pathogens could modulate neuronal signaling to potentiate their pathogenesis and facilitate their spread to other hosts. Defining how pathogens modulate pain and itch has critical implications for sensory neurobiology and our understanding of host-microbe interactions.
Animals ; Humans ; Infection ; complications ; etiology ; pathology ; Neurons ; pathology ; Pain ; etiology ; pathology ; Pruritus ; etiology ; pathology

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

Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
Mice ; Animals ; Gyrus Cinguli/physiology* ; Pruritus/pathology* ; Mesencephalon ; Cerebral Cortex/pathology* ; Neurons/pathology*

OBJECTIVETo investigate the pathogenic and clinical presentation and laboratory tests of bullous rash in hand, foot and mouth disease (HFMD) in Xi'an from January 2013 to December 2014 by retrospective analysis.

METHODA total of 224 specimens were collected from clinically diagnosed HFMD cases who were characterized by widespread mucocutaneous bullous reactions in Xi'an Children's Hospital from January 2013 to December 2014, the identification and subtyping of the isolates were conducted with real-time fluorescent quantitative RT-PCR. A retrospective analysis was performed to analyze the clinical presentation, laboratory tests and late follow-up problems of the HFMD.

RESULTIn the clinically diagnosed HFMD cases who were characterized by widespread mucocutaneous bullous reactions, 207 were caused by coxsackievirus A6 (CA6), accounting for 92. 4% of all cases with bullous, 4 were caused by enterovirus 71 (EV71), accounting for 1.8%, 10 were caused by coxsackievirus A16 (CA16), accounting for 4. 5%; 4 cases were negative for these viruses. In the cases positive for intestinal virus-nucleic acid, 130 were male, 90 were female; male to female ratio was 1. 44: 1, 203 were <5 years old, accounting for 92. 3%. Leukocytosis was found in 75 cases (34. 1%); high-sensitivity C-reactive protein (hsCRP) increased in 200 cases (90. 9%); elevated myocardial enzyme CK-MB was found in 35 cases (15. 9%), alanine aminotransferase increased in 15 cases (6. 8%); 187 cases had fever (85. 0%). None of the cases had serious complications such as encephalitis or myocarditis. In the course of the critical phase bullous rash or large vesicle-like changes, obvious itching, and facial rash appeared. After the fluid in the bullae was absorbed or the bullae ruptured or became ulcerated, scar formation and large areas of exfoliation occurred, with no effusion on the newly formed epithelium in the base, without significant pigmentation on later follow-up. In the late follow up process, 52 cases in CA6-positive patients (25. 1%) developed onychomadesis within 2-4 weeks after onset, 1 to 8 nails, an average of 4. 3 fell off, new nails grew, the nail bed showed no structural abnormalities and hyperplasia after falling off, the surface was smooth, had no hypertrophy, left no sequelae.

CONCLUSIONThe pathogen in HFMD characterized by widespread bullous reactions was mainly the CA6, this kind of HFMD was mainly mild type, with significant itching, later the bullae may have scar formation and skin exfoliation, in some cases onychomadesis may occur.

Child ; Enterovirus A, Human ; Enterovirus Infections ; pathology ; Exanthema ; pathology ; Female ; Fever ; Hand, Foot and Mouth Disease ; pathology ; Humans ; Male ; Pruritus ; Retrospective Studies

PURPOSE: To present a case of ocular sparoganosis presenting as itching sensation. METHODS: A 60-year-old woman presented for removal of an itchy subconjunctival mass in her left eye. Her ocular findings were normal, except for a subconjunctival mass (1.5 x 1.5 mm). RESULTS: A parasite excised from the subconjunctival mass was identified as a sparganum, by microscopic examination after hematoxylin-eosin staining. The mummified parasite was identified as the plerocercoid phase of the sparganum, by microscopy. CONCLUSIONS: Although rare, parasitic disease should be suspected in a palpable subconjunctival mass unresponsive to the medical treatment.
Sparganosis/*complications/pathology/surgery ; Pruritus/*etiology ; Ophthalmologic Surgical Procedures ; Middle Aged ; Korea ; Humans ; Female ; Eye/*parasitology

Humans ; Lymphoma, T-Cell, Cutaneous/complications* ; Neuroglia ; Pruritus/pathology* ; Skin Neoplasms/complications* ; Spinal Cord/pathology* ; Sympathetic Nervous System

OBJECTIVEIn order to improve the cognition and early diagnosis of primary biliary cirrhosis (PBC), we investigated clinical and pathological characteristics of PBC.

METHODSClinical data of 37 PBC patients together with pathological findings of 20 PBC patients were reviewed.

RESULTSAmong the 37 patients, 35 were women and the mean age at diagnosis was (53.4 8.9) years. The most frequent clinical presentations were jaundice (70.3%), fatigue (70.3%), and pruritus (56.8%). Serum glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) levels were markedly elevated in all patients (P50 was 467.50 U/L and 424.00 U/L, respectively). Among the 37 cases, 35 (94.6%) had total bile acids elevation, 32 (86.5%) had serum cholesterol elevation and 32 (86.5%) serum IgM elevation, 34 (91.9%) were positive for anti-mitochondrial antibody (AMA) and/or AMA-M2. Liver biopsy in 20 PBC patients mainly found: fibrosis in 17 cases (85%), interlobular bile duct lesions in 13 (65%), lobular mononuclear inflammation in 13 (65%), lymphocytic hepatocellular piecemeal necrosis in 10 (50%), and bile pigment accumulation in 9 (45%). The results of nonparametric test showed that GGT was related with pathological stage (P=0.002) and interlobular bile duct lesions (P=0.01).

CONCLUSIONSPBC is mostly found in middle-aged women. Accurate and prompt diagnosis of PBC should be based on the clinical presentation, biochemical and immunological indexes, and hepatic pathological changes. The level of GGT may partly reflect the severity of the histological lesions

Bile Acids and Salts ; Biopsy ; Fatigue ; Female ; Humans ; Liver Cirrhosis, Biliary ; pathology ; Male ; Middle Aged ; Mitochondria ; Portal System ; Pruritus ; gamma-Glutamyltransferase

Tuberculosis continues to be the biggest public health problem worldwide. Tuberculosis verrucosa cutis (TVC) is a verrucose form of cutaneous tuberculosis that occurs in previously sensitised individuals due to exogenous reinfection with Mycobacterium tuberculosis or Mycobacterium bovis, and it reflects good cell-mediated immunity. An elderly man presented with multiple fungating growths, which were painless but associated with mild itching and serous discharge, on the right foot for 40 years. The lesions were free from deeper structures and no inguinal lymphadenopathy was observed. A provisional diagnosis of epithelioma was made based on the features described. However, incisional biopsy indicated that the lesions were tuberculous. As part of the anti-tubercular therapy, the lesions were excised and the wounds covered with split-thickness skin graft. The patient's recovery was uneventful, with no graft loss or infection reported. This case illustrates the importance of recognising cutaneous forms of tuberculosis, especially TVC, as an important differential diagnosis of epithelioma.
Biopsy ; Carcinoma ; diagnosis ; Diagnosis, Differential ; Humans ; Male ; Middle Aged ; Mycobacterium bovis ; Mycobacterium tuberculosis ; Pruritus ; Skin ; pathology ; Tuberculosis, Cutaneous ; diagnosis

PURPOSE: We report a case of recurrent ocular thelaziasis by Thelazia callipaeda. CASE SUMMARY: A 71-year-old male visited the ophthalmic clinic, complaining of itching, a foreign body sensation, and irritation in the right eye. He was previously diagnosed with Thelazia callipaeda infection, 3 months prior, at another hospital. A parasite, shaped like a thin small thread, was found in the conjunctival sac of his right eye, with active movement. The parasite was identified as Thelazia callipaeda by pathology. Four months after removal of the parasite, symptoms relapsed in the same eye. Two parasites were rediscovered and removed. Since then, no additional specific sign related to the parasite has been noted in follow- up examinations. CONCLUSIONS: Due to frequent recurrence of infections caused by the short life cycle of the parasite, monthly follow-up examinations are required for at least 1 year after discovery of the parasite.
Aged ; Follow-Up Studies ; Foreign Bodies ; Humans ; Lacrimal Apparatus ; Life Cycle Stages ; Male ; Parasites ; Pathology ; Pruritus ; Recurrence ; Sensation ; Thelazioidea