Effect of CXCL12/CXCR4 signaling on neuropathic pain after chronic compression of dorsal root ganglion.

Neuropathic pain is a complex, chronic pain state that often accompanies tissue damage, inflammation or injury of the nervous system. However the underlying molecular mechanisms still remain unclear. Here, we showed that CXCL12 and CXCR4 were upregulated in the dorsal root ganglion (DRG) after chronic compression of DRG (CCD), and some CXCR4 immunopositive neurons were also immunopositive for the nociceptive neuronal markers IB4, TRPV1, CGRP, and substance P. The incidence and amplitude of CXCL12-induced Ca2+ response in primary sensory neurons from CCD mice was significantly increased compared to those from control animals. CXCL12 depolarized the resting membrane potential, decreased the rheobase, and increased the number of action potentials evoked by a depolarizing current at 2X rheobase in neurons from CCD mice. The mechanical and thermal hypernociception after CCD was attenuated by administration of a CXCR4 antagonist AMD3100. These findings suggest that CXCL12/CXCR4 signaling contributes to hypernociception after CCD, and targeting CXCL12/CXCR4 signaling pathway may alleviate neuropathic pain.

Altered serum levels of TNF-α, IL-6 and IL-18 in manic, depressive, mixed state of bipolar disorder patients.

Bipolar disorder (BD) is associated with alterations of cytokines in the immune system. The aim of this study was to assess the serum levels of TNF-α, IL-6 and IL-18 in manic, depressive, mixed state patients of BD. The correlations between the serum cytokines levels with the demographic characteristics and the psychiatric symptoms were also assessed. We measured serum TNF-α, IL-6 and IL-18 levels using an enzyme-linked immunosorbent assay (ELISA) from 59 BD patients (37 in manic state, 12 in depressive state, 10 in mixed state) and 80 healthy control subjects. The psychotic symptoms of BD were assessed using the Hamilton Depression Scale (HAMD) and the Young Mania Rating Scale (YMRS). The results showed that serum TNF-α and IL-6 levels in manic, depressive and mixed state BD patients were significantly higher than that in controls, while serum IL-18 level was only significantly higher in depressive patients. Serum IL-6 level was significantly positively correlated with YMRS scores in manic episode as well as in mixed episode. When gender and age were added as potentially confounding covariate terms, the differences between controls and each mood state patients were still significant. Our findings provided additional evidence that elevated TNF-α, IL-6 and IL-18 pathway activities may be involved in the psychopathology of BD. Due to the lack of controlling important confounding factors, such as BMI, smoking status and alcohol use, further studies are required to confirm the roles of TNF-α, IL-6 and IL-18.

Relationship of serum levels of TNF-α, IL-6 and IL-18 and schizophrenia-like symptoms in chronic ketamine abusers.

OBJECTIVE: Exposing to NMDAR receptor antagonists, such as ketamine, produces schizophrenia-like symptoms in humans and deteriorates symptoms in schizophrenia patients. Meanwhile, schizophrenia is associated with alterations of cytokines in the immune system. This study aims to examine the serum TNF-α, IL-6 and IL-18 levels in chronic human ketamine users as compared to healthy subjects. The correlations between the serum cytokines levels with the demographic, ketamine use characteristics and psychiatric symptoms were also assessed. METHODS: 155 subjects who fulfilled the criteria of ketamine dependence and 80 healthy control subjects were recruited. Serum TNF-α, IL-6 and IL-18 levels were measured using an enzyme-linked immunosorbent assay (ELISA). The psychiatric symptoms of the ketamine abusers were assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 and IL-18 levels were significantly higher, while serum TNF-α level was significantly lower among ketamine users than among healthy controls (p<0.05). Serum TNF-α levels showed a significant negative association with PANSS total score (r=-0.210, p<0.01) and negative subscore (r=-0.300, p<0.01). No significant association was found between PANSS score and serum levels of IL-6 and IL-18. CONCLUSIONS: Serum levels of TNF-α, IL-6 and IL-18 were altered in chronic ketamine abusers which may play a role in schizophrenia-like symptoms in chronic ketamine abusers.

Attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members and the general population in a large city in Guangzhou, China.

PURPOSE: Stigma towards people with mental illness is believed to be widespread in low and middle income countries. METHODS: This study assessed the attitudes towards people with mental illness among psychiatrists, psychiatric nurses, involved family members of patients in a psychiatric facility and the general public using a standard 43-item survey (N = 535). Exploratory factor analysis identified four distinctive attitudes which were then compared using Analysis of Covariance (ANCOVA) among the four groups, all with ties to the largest psychiatric facility in Guangzhou, China, adjusting for sociodemographic differences. RESULTS: Four uncorrelated factors expressed preferences for 1) community-based treatment, social integration and a biopsychosocial model of causation, 2) direct personal relationships with people with mental illness, 3) a lack of fear and positive views of personal interactions with people with mental illness, 4) disbelief in superstitious explanations of mental illness. Statistically significant differences favored community-based treatment and biopsychosocial causation (factor 1) among professional groups (psychiatrists and nurses) as compared with family members and the general public (p < 0.001); while family members, unexpectedly, showed far weaker personal preferences for direct personal relationships with people with mental illness than all three other groups (p < 0.001). CONCLUSION: Both psychiatrists and nurses showed greater support for social integration and biopsychosocial understandings of mental illness than the lay public, most likely because of their training and experience, while family members showed the least positive attitudes towards direct personal relationships with people with mental illness. These findings suggest support for a more extensive, formal system of care that gives family members some distance from the problems of their relatives and support in their care.