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Profiling of how nociceptor neurons detect danger; new and old foes.

The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a common language of ligands and receptors, the immune and sensory nervous systems work in concert to accomplish such protective functions. While this bidirectional communication helps to protect from danger, it can contribute to disease pathophysiology. Thus, the somatosensory nervous system is anatomically positioned within primary and secondary lymphoid tissues and mucosa to modulate immunity directly. Upstream of this interplay, neurons detect danger which prompts the release of neuropeptides initiating i) defensive reflexes (ranging from withdrawal response to coughing); and ii) chemotaxis, adhesion and local infiltration of immune cells. The resulting outcome of such neuro-immune interplay is still ill-defined, but consensual findings start to emerge and support neuropeptides as blockers of T 1-mediated immunity but also as drivers of T 2 immune responses. However, the modalities detected by nociceptors revealed broader than mechanical pressure and temperature sensing and include signals as various as cytokines and pathogens to immunoglobulins and even microRNAs. Along these lines, we aggregated various dorsal root ganglion sensory neurons expression profiling datasets supporting such wide-ranging sensing capabilities and to help identify novel danger detection modalities of these cells. Thus, revealing unexpected aspects of nociceptor neurons biology might prompt the identification of novel drivers of immunity, means to resolve inflammation and strategies to safeguard homeostasis. This article is protected by copyright. All rights reserved.

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Brain mechanisms of social touch-induced analgesia in females.

Supportive touch has remarkable benefits in childbirth and during painful medical procedures. But does social touch influence pain neurophysiology, ie, the brain processes linked to nociception and primary pain experience? What other brain processes beyond primary pain systems mediate their analgesic effects? In this study, women (N = 30) experienced thermal pain while holding their romantic partner's hand or an inert device. Social touch reduced pain and attenuated functional magnetic resonance imaging activity in the Neurologic Pain Signature (NPS)-a multivariate brain pattern sensitive and specific to somatic pain-and increased connectivity between the NPS and both somatosensory and "default mode" regions. Brain correlates of touch-induced analgesia included reduced pain-related activation in (1) regions targeted by primary nociceptive afferents (eg, posterior insula, and anterior cingulate cortex); and (b) regions associated with affective value (orbitofrontal cortex), meaning (ventromedial prefrontal cortex [PFC]), and attentional regulation (dorsolateral PFC). Activation reductions during handholding (vs holding a rubber device) significantly mediated reductions in pain intensity and unpleasantness; greater pain reductions during handholding correlated with greater increases in emotional comfort, which correlated with higher perceived relationship quality and (a trend toward) greater perceived closeness with the romantic partner. The strongest mediators of analgesia were activity reductions in a brain circuit traditionally associated with stress and defensive behavior in mammals, including ventromedial and dorsomedial PFC, rostral anterior cingulate cortex, amygdala/hippocampus, hypothalamus, and periaqueductal gray matter. Social touch affects core brain processes that contribute to pain and pain-related affective distress in females, and should be considered alongside other treatments in medical and caregiving contexts.

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Depression comorbid with hyperalgesia: Different roles of neuroinflammation induced by chronic stress and hypercortisolism.

Recent studies have indicated that inflammatory pathways and hypothalamic-pituitary-adrenal (HPA) axis function may be responsible for the interaction between pain and depression.

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The Relation of Self-Compassion to Functioning among Adults with Chronic Pain.

Previous research has shown that self-compassion is associated with improved functioning and health outcomes among multiple chronic illnesses. However, the role of self-compassion in chronic pain-related functioning is understudied. The present study sought to understand the association between self-compassion and important measures of functioning within a sample of patients with chronic pain. Treatment-seeking individuals (N= 343 with chronic pain) that were mostly White (97.9%) and female (71%) completed a battery of assessments that included the Self-Compassion Scale (SCS), as well as measures of pain-related fear, depression, disability, pain acceptance, success in valued activity, and use of pain coping strategies. Cross-sectional multiple regression analyses that controlled for age, sex, pain intensity, and pain duration, revealed that self-compassion accounted for a significant and unique amount of variance in all measures of functioning (r range: .07 – .32, all p < .001). Beta weights indicated that higher self-compassion was associated with lower pain-related fear, depression, and disability, as well as greater pain acceptance, success in valued activities, and utilization of pain coping strategies. These findings suggest that self-compassion may be a relevant adaptive process in those with chronic pain. Targeted interventions to improve self-compassion in those with chronic pain may be useful. SIGNIFICANCE: Self-compassion is associated with better functioning across multiple general and pain-specific outcomes, with the strongest associations among measures related to psychological functioning and valued living. These findings indicate that self-compassion may be an adaptive process that could minimize the negative impact of chronic pain on important areas of life. This article is protected by copyright. All rights reserved.

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Self-regulatory ability, fatigue, and the experience of pain: Mechanistic insights from pain-free undergraduates.

Self-regulatory (SR) ability is an important resource for managing pain, but chronic pain patients experience chronic self-regulatory fatigue even when they are not in pain. Pressure pain thresholds (PPT) and pain inhibition are two mechanisms that differentiate people with and without chronic pain. It was hypothesized that trait SR ability would be associated with higher PPT and better pain inhibition and that PPT and pain inhibition would be lower following high versus low SR fatigue. Three studies tested these hypotheses. Study 1 had 240 pain-free undergraduates complete measures of trait SR ability and PPT; 122 also provided data on pain inhibition. Study 2 had 38 of Study 1's participants return for two additional sessions in which they underwent PPT testing under conditions of high or low SR fatigue (within-person, counterbalanced). Study 3 repeated these procedures with pain inhibition as the outcome (n = 39). Results revealed that individual differences in SR ability were not associated with PPT or pain inhibition (all ps > 0.05). Within people, neither PPT (F(1, 36) = 1.57, p = 0.22) nor pain inhibition (F(1, 37) = 1.79, p = 0.19) were significantly different under conditions of low versus high SR fatigue. Results do not support the hypotheses that PPT or pain inhibition associate with individual differences in trait SR ability or transient changes in state SR fatigue in the absence of pain. Instead, the SR deficits in chronic pain patients may arise from the experience of chronic pain.

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The diagnostic accuracy of headache measurement instruments: A systematic review and meta-analysis focusing on headaches associated with musculoskeletal symptoms.

To systematically review the available literature on the diagnostic accuracy of questionnaires and measurement instruments for headaches associated with musculoskeletal symptoms.

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Depression Trends in Patients with Chronic Pain: An Analysis of the Nationwide Inpatient Sample.

Chronic pain remains a major public health issue that affects the lives of many worldwide, including patients with chronic pain. Comorbidities like depression have been associated with decreased quality of sleep, decreased enjoyment of life activities, increased anxiety, and decreased efficacy in treatments among patients with chronic pain. Despite these associations, the trends and demographic characteristics of patients with chronic pain with depression is yet to be investigated.

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Weeding Out the Problem: The Impact of Preoperative Cannabinoid Use on Pain in the Perioperative Period.

The recreational and medical use of cannabinoids has been increasing. While most studies and reviews have focused on the role of cannabinoids in the management of acute pain, no study has examined the postoperative outcomes of surgical candidates who are on cannabinoids preoperatively. This retrospective cohort study examined the impact of preoperative cannabinoid use on postoperative pain scores and pain-related outcomes in patients undergoing major orthopedic surgery.

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Altered monoamine levels in the dorsal striatum of the rat are associated with alterations in behavioural selection and motivation following peripheral nerve injury and acute stress.

Chronic neuropathic pain and psychological stress interact to compromise goal-directed control over behaviour following mild psychological stress. The dorsomedial (DMS) and dorsolateral (DLS) striatum in the rat are crucial for the expression of goal-directed and habitual behaviours, respectively. This study investigated whether changes in monoamine levels in the DMS and DLS following nerve injury and psychological stress reflect these behavioural differences. Neuropathic pain was induced by a chronic constriction injury (CCI) of the sciatic nerve in Sprague-Dawley rats. Acute stress was induced using a 15 minute restraint. Behavioural flexibility was assessed using the outcome devaluation paradigm. Noradrenaline, serotonin, dopamine and associated metabolites were measured bilaterally from the DLS and DMS. In uninjured rats, restraint increased dopaminergic markers in the left and serotonergic markers in the right of both the DMS and DLS, indicating a possible left hemisphere-mediated dominance. CCI led to a slightly different lateralised effect, with a larger effect in the DMS than in the DLS. Individual differences in behavioural flexibility following CCI negatively correlated with dopaminergic markers in the right DLS, but positively correlated with these markers in the left DMS. A combination of CCI and restraint reduced behavioural flexibility, which was associated with the loss of the left/DMS dominance. These data suggest that behavioural flexibility following psychological stress or pain is associated with a left hemisphere dominance within the dorsal striatum. The loss of behavioural flexibility following the combined stressors is then associated with a transition from left to right, and DMS to DLS dominance. This article is protected by copyright. All rights reserved.

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Perioperative use of opioids: Current controversies and concerns.

In the midst of an epidemic of opioid abuse and overdose-related morbidity and mortality, the use of opioids remains the most common means of providing analgesia in the perioperative period. In this article, we review the risks and benefits of opioid use in preoperative, intraoperative and post-operative phases of care. Furthermore, we describe the role that surgeons and anaesthesiologists can play in reducing perioperative opioid use and mitigate their adverse effects, from both an individual and a population health perspective.

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