Pathological pain, normally referring to tissue injury-induced inflammatory pain and nerve injury-induced neuropathic pain, is an expression of neural plasticity. Injuries and intense noxious stimuli result in pain hypersensitivity,which is contributed by peripheral sensitization (increased sensitivity of primary sensory nociceptors) and central sensitization (increased sensitivity of spinal dorsal horn and other CNS neurons). Activation of several protein kinases causes both forms of sensitization via posttranslational regulation, such as phosphorylation of key membrane receptors and channels. In particular, activation of multiple signal cascades converge on the activation of MAPK (mitogen-activated protein kinase).Activation of MAPK family members of ERK and p38 by nociceptive activity, growth factors, and inflammatory mediators in primary sensory and secondary order neurons, not only results in posttranslational modification, but also increases the expression of numerous genes via transcriptional and non-transcriptional regulation. Eventually this activation contributes to the development and maintenance of heightened pain sensitivity following injury.

The pain experience includes a sensory-discriminative and an emotional-affective component. The sensory dimension describes the quality, intensity, and spatio-temporal characteristics of the sensation. The affective dimension refers to the unpleasantness or aversion of sensation. The great progress at the genic, molecular, cellular, and systemic level on the study of the sensory dimension of pain has been made over past four decades. However, to consider only the sensory features of pain, and ignore its motivational and affective properties, is to look at only part of the problem. A line of clinic observations indicate that the patients with chronic pain suffer from much more affective disturbance than pain itself. Obviously, physiological arousal and hypervigilance to pain cause negative affect, such as fear, anxiety, angry, worry, aversion, even tendency of suicide, these negative affective states in turn enhance pain sensation. Therefore, the mechanisms underlying the affective dimension of pain have recently received more attention. In order to deepen and expand our understanding of the nature of pain, this review summarizes the main findings regarding affective component of pain in neuroanatomy, neurophysiology, and cell biochemistry

Animals ; Humans ; Pain ; physiopathology ; Pruritus ; physiopathology

Humans ; Pain ; Pruritus

Adult ; Benzene ; poisoning ; Chronic Disease ; Cytochrome P-450 CYP2E1 ; genetics ; Female ; Humans ; Leukocyte Count ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Polymorphism, Genetic

Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer’s disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. PD-1 signaling suppresses the CNS immune response via resident microglia and infiltrating peripheral immune cells. Notably, PD-1 is also widely expressed in neurons and suppresses neuronal activity via downstream Src homology 2 domain-containing protein tyrosine phosphatase 1 and modulation of ion channel function. An improved understanding of PD-1 signaling in the cross-talk between glial cells, neurons, and peripheral immune cells in the CNS will shed light on immunomodulation, neuromodulation, and novel strategies for treating brain diseases.

Humans ; Ion Channels ; Pain ; Pressure ; TRPM Cation Channels ; TRPV Cation Channels ; Temperature

OBJECTIVETo investigate the mechanism for the apoptosis of hippocampus neuron induced by hypothyroidism in perinatal rats.

METHODSHypothyroidism was induced by administration of propylthiouracil (PTU, 50 mg/d) solution to the dams from gestational day 15 by gavage. Pups from both hypothyroid and control groups were harvested at 1, 5, 10 and 15d, respectively. Blood samples were collected at the time of death for the determination of thyroid hormone. Serum free triiodothyronine (FT(3)) and free thyroxine (FT(4)) were measured by chemoluminescence. Hippocampus specimens were collected from the control and hypothyroid pups.Mitochondia was examined under transmission electron microscopy. Translocation of apoptogenic molecules (Bax, cytochrome C and AIF) and activation of caspase-3 were analyzed by Western Blotting.

RESULTSignificantly low circulating FT(3) and FT(4) levels confirmed the hypothyroid status of the experimental pups. Electron microscopy showed that altered morphology of mitochondria significantly increased under hypothyroid conditions. The expression of Bax in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.05),and significantly higher in mitochondria (P<0.001). The expression of cytochrome c in the cytosol of hypothyroid pups was significantly higher than that of control pups at all stages of development (1,10 and 15 d:P<0.05, 5d: P<0.001), and lower in mitochondria (P<0.05). The expression of AIF in the cytosol of hypothyroid pups was higher than that of control pups at all stages of development (P<0.001), and significantly lower in mitochondria (1, 5d: P<0.001, 10, 15 d: P<0.01). he expression of caspase-3 P20 in the cytosol of hypothyroid pups was significantly higher as compared with that of the age-matched controls (1, 15d: P<0.01, 5,1 0 d: P<0.001).

CONCLUSIONThe intrinsic death pathway in mitochondria may be one of the mechanisms with which hypothyroid induces apoptosis of hippocampus neuron in developing rats.

Animals ; Animals, Newborn ; Apoptosis ; physiology ; Female ; Hippocampus ; pathology ; Hypothyroidism ; chemically induced ; pathology ; Neurons ; pathology ; Pregnancy ; Pregnancy Complications ; pathology ; Propylthiouracil ; Rats ; Rats, Wistar

Objective To investigate the changes and clinical significance of peripheral blood mucosal-associated invariant T(MAIT)cells in children with influenza.Methods Children with influenza who received treatment in the outpatient and inpatient departments of a children's hospital from January to May 2023 were selected and divided into the common type group and the severe type group.Healthy children who underwent physical examination in this hospital during the same period were selected as the healthy control group.Within 24 hours after admission,children's venous blood was drawn for testing;ratios of MAIT cells(CD3+CD161+TCRVα7.2+cells)and MAIT cells expressing PD-1,CD69,perforin,and CD107 α were tested by flow cytometry,respectively.Differences among all the groups were compared.Results Compared with the control group,the proportion of peripheral blood MAIT cells in children with common and severe influenza gradually decreased,while the proportion of CD69-ex-pressing and perforin-positive MAIT cells increased gradually.Differences were statistically significant(all P＜0.05).There was no statistically significant difference in the proportion of MAIT cells expressing CD107(P＞0.05).The proportion of PD-1 positive MAIT cells increased(P＜0.05),but there was no statistically significant difference be-tween the common type and severe type groups(P＞0.05).Conclusion The decrease of peripheral blood MAIT cells accompanied with immune activation plays a role in the pathogenesis of influenza.

OBJECTIVETo investigate the relationship between the mRNA expression levels of p53-mediating DNA damage and repair genes in the peripheral blood lymphocytes of workers and their exposures to benzene in their working environment.

METHODSThe mRNA expression levels of p53 and related genes were determined by SYBR Green I chimeric fluorescence quantitative real-time RT-PCR analysis in peripheral blood lymphocytes of 72 workers, who were classified into group A (46 direct exposure to benzene) and group B (26 indirect exposure to benzene) based on their positions, and 29 controls. The differences of gene expression levels were analyzed by software REST 2005. Meanwhile, the peripheral blood leukocytes, hemoglobin and platelet of workers and controls were counted. Benzene content was measured in the samples of toluene, used as raw material, and spraying agents and benzene, toluene and xylene concentrations in the air of workplaces were monitored.

RESULTSThere were no significant differences in the mRNA expression levels of p53, Ku80, Ape1 and Mdm-2 between group A or group B and control group (P > 0.05). The expression up-regulation of p21 mRNA was found, but without significant difference (P > 0.05). However, the mRNA expression levels of Rad51, Bcl-2, Bax, Xpa and Xpc in group A and Rad51 in group B were downregulated significantly (P < 0.05 or P < 0.01). Moreover, both the counts of white blood cell, hemoglobin and platelet in group A were (4.93 +/- 1.27) x 10(9)/L, (123.97 +/- 11.80) g/L and (124.02 +/- 41.22) x 10(9)/L respectively and platelet in group B (135.80 +/- 39.44) x 10(9)/L were significantly lower than in control group (P < 0.05 or P < 0.01).

CONCLUSIONThe mRNA expression levels of some p53-mediating DNA damage and repair genes are downregulated in the workers chronically exposed to low benzene concentration. The working environment impacts on health of group A workers are greater than the ones of group B.

Adult ; Benzene ; adverse effects ; DNA Damage ; DNA Repair ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Occupational Exposure ; adverse effects ; RNA, Messenger ; genetics ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult