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Introduction: Smoking is associated with several diseases and affects the immune system. Recently, published data demonstrate an involvement of T helper 17 cells (Th17) and regulatory T cells (Tregs) in the pathogenesis of chronic pain and pain intensity. The role of these T-cell subsets in smoking patients with chronic pain is nebulous so far. We therefore analyzed Th17 cells and Tregs in smokers and nonsmokers with chronic pain., Methods: Analyses of T-cell subsets, mRNA expression and T-cell related cytokine profiles were done in 44 patients with chronic pain. Twenty-two of these patients were smokers. Numbers of T-cell subsets were quantified by flow cytometry. mRNA expression of the Th17- (RAR-related orphan receptor gamma) and Treg (forkhead box protein P3)-specific transcription factors was determined by quantitative real-time PCR, and levels of cytokines were measured by Human Cytokine Multiplex Immunoassay., Results: Compared to nonsmokers, smokers showed significantly enhanced pain levels. On cellular basis, the number of pro-inflammatory Th17 cells (smokers: 2.2 ± 2.5% vs. nonsmokers: 0.5 ± 0.4%; p = .04) was increased, whereas the number of anti-inflammatory Tregs (smokers: 2.5 ± 0.9% vs. nonsmokers: 3.1 ± 1.1%; p = .02) was significantly decreased, resulting in an altered Th17/Treg ratio (Th17/Treg ratio: 0.9 ± 1.0 in smokers vs. 0.2 ± 0.1 in nonsmokers; p < .01). These findings were confirmed by quantitative real-time PCR. Analyses of cytokines revealed only marginal changes., Conclusions: In patients with chronic pain, smoking is associated with enhanced pain levels together with an imbalance of the Th17/Treg ratio. The shift of the Th17/Treg ratio toward inflammation may explain in part the increased pain intensity in these patients., Implications: Smoking is associated with increased pain levels and a pro-inflammatory Th17/Treg shift. The altered Th17/Treg ratio in smoking patients with chronic pain may partly explain their increased pain intensity., German Clinical Trial Register (drks): Registration Trial DRKS00005954., (© The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite substantial progress, pathogenesis and therapy of chronic pain are still the focus of many investigations. The ATP-gated P2X7 receptor (P2X7R) has previously been shown to play a central role in animal models of nociceptive inflammatory and neuropathic pain. Recently, we found that the adaptive immune system is involved in the pathophysiology of chronic nociceptive and neuropathic pain in humans. So far, data regarding P2X7R expression patterns on cells of the adaptive immune system of pain patients are scarce. We therefore analyzed the P2X7R expression on peripheral blood lymphocytes and monocytes, as well as serum levels of IL-1β in patients suffering from chronic nociceptive and neuropathic pain in comparison to healthy volunteers in order to identify individuals who might benefit from a P2X7R modulating therapy.Methods: P2X7R messenger RNA (mRNA) and protein expression were determined in patients with either chronic nociceptive low back pain (CLBP) or neuropathic pain (NeP), and in healthy volunteers by quantitative real-time PCR (qPCR) and by fluorescence-assisted cell-sorting (FACS), respectively. IL-1β serum levels were measured with a multiplex cytokine assay.Results: Compared to healthy volunteers, P2X7R mRNA (1.6-fold, p = 0.038) and protein levels were significantly increased on monocytes (NeP: 24.6 ± 6.2, healthy volunteers: 17.0 ± 5.4; p = 0.002) and lymphocytes (NeP: 21.8 ± 6.5, healthy volunteers: 15.6 ± 5.2; p = 0.009) of patients with NeP, but not in patients with CLBP. Similarly, IL-1β serum concentrations were significantly elevated only in NeP patients (1.4-fold, p = 0.04).Conclusions: A significant upregulation of P2X7R and increased IL-1β release seems to be a particular phenomenon in patients with NeP. P2X7R inhibitors may therefore represent a potential option for the treatment of this frequently intractable type of pain. German Clinical Trial Register (DRKS): Registration Trial DRKS00005954. [ABSTRACT FROM AUTHOR]

Abstract: Background: The amygdala plays an important role in the processing of chronic pain and pain memory formation. Particularly, it is involved in the emotional and affective components of the pain circuitry. The role of kappa opioid receptors in these pain conditions is only partly known. The present study investigates the effect of kappa receptor activation on synaptic transmission and synaptic plasticity in the amygdala. Methods: Electrophysiological in vitro experiments were carried out in brain slices of male C57BL/6JOlaHsd mice. The effect of the kappa opioid receptor agonist U50,488H (5μM) and the selective kappa opioid receptor antagonist nor-BNI (3μM) on field potential (FP) amplitude and the induction of long-term potentiation (LTP) in the basolateral amygdala (BLA) was examined. Results: High frequency stimulation (HFS) of afferents in the lateral amygdala with two trains of 100 pulses at 50Hz increased the FP amplitudes to 119±2% (mean±SEM; n =6) in the BLA. U50,488H decreased synaptic transmission (baseline: 100±0.5%; U50,488H: 86.3±2.4%; n =6) and blocked the induction of LTP (U50,488H: 100±4.1%; HFS: 102.6±7%; n =6). The effect on synaptic transmission and on LTP was completely reversed or prevented by application of nor-BNI, which itself had no effect on synaptic transmission or the induction of LTP. Conclusion: Kappa opioid receptor activation decreases synaptic transmission and inhibits the induction of LTP in the BLA of the mouse. These findings may be associated with the effects of kappa opioid agonists in chronic pain and pain memory formation. [Copyright &y& Elsevier]

Objective. Functional restoration programs for chronic low back pain (CLBP) have been shown to be successful in improving function and, to a lesser extent, in reducing pain. The Munich Functional Restoration Program (MFRP) is a 4-week outpatient program designed to reduce pain and to improve health-related quality of life in patients with a long history of CLBP. Design. In a retrospective matched concurrent-controls therapeutic study, 44 patients with CLBP, who had either undergone MFRP or received an outpatient standard treatment (control) after initial evaluation at the pain center, completed questionnaires 1 year after the respective therapy (t1). The following parameters were assessed: health-related quality of life with Short Form-36 (SF-36), Pain Disability Index (PDI), Numeric Rating Scale (NRS) for pain, depression with the Center for Epidemiological Studies Depression Test (CES-D), and occupational situation. These data were compared with baseline values assessed by a questionnaire completed before starting the respective treatment (baseline, t0). Results. Compared with control, NRS and PDI were significantly better in patients completing the MFRP. Patients of the MFRP group showed also a significant reduction in CES-D as well as an improvement in three of eight SF-36 subscales. No changes were detected in the control group receiving standard treatment. Conclusions. Compared with standard treatment, a functional restoration program for CLBP significantly improves some aspects of health-related quality of life. It results in a decrease of pain and pain-related disability even in patients with a long history of CLBP. [ABSTRACT FROM AUTHOR]

Complex regional pain syndrome (CRPS) develops after-limb injury, with persistent pain and deficits in movement frequently co-occurring. The striatum is critical for mediating multiple mechanisms that are often aberrant in CRPS, which includes sensory and pain processing, motor function, and goal-directed behaviors associated with movement. Yet, much remains unknown with regards to the morphological and functional properties of the striatum and its subregions in this disease. Thus, we investigated 20 patients (15 female, age 58 ± 9 years, right-handed) diagnosed with chronic (6+ months of pain duration) CRPS in the right hand and 20 matched, healthy controls with anatomical and resting-state, functional magnetic resonance imaging. In addition, a comprehensive clinical and behavioral evaluation was performed, where each participant's pain, motor function, and medical history were assessed. Complex regional pain syndrome patients harbored significant abnormalities in hand coordination, dexterity, and strength. These clinical pain- and movement-related findings in CRPS patients were concomitant with bilateral decreases in gray matter density in the putamen as well as functional connectivity increases and decreases among the putamen and pre-/postcentral gyri and cerebellum, respectively. Importantly, higher levels of clinical pain and motor impairment were associated with increased putamen-pre-/postcentral gyri functional connectivity strengths. Collectively, these findings suggest that putaminal alterations, specifically the functional interactions with sensorimotor structures, may underpin clinical pain and motor impairment in chronic CRPS patients. [ABSTRACT FROM AUTHOR]