Pain
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Opioid use in chronic pain treatment is complex, as patients may derive both benefit and harm. Identification of individuals currently using opioids in a problematic way is important given the substantial recent increases in prescription rates and consequent increases in morbidity and mortality. The present review provides updated and expanded information regarding rates of problematic opioid use in chronic pain. ⋯ Abuse was reported in only a single study. Only 1 difference emerged when study methods were examined, where rates of addiction were lower in studies that identified prevalence assessment as a primary, rather than secondary, objective. Although significant variability remains in this literature, this review provides guidance regarding possible average rates of opioid misuse and addiction and also highlights areas in need of further clarification.
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An important property of the nociceptive system is its plasticity, ie, the ability to change in an experience-dependent manner, which is implicated in the transition from acute pain to chronic pathological pain. Disease-induced plasticity can occur at both structural and functional levels and manifests as changes in individual molecules, synapses, cellular function, and network activity. In this short review, the author discusses how synaptic plasticity may mediate pathophysiological alterations linked to chronic pain by virtue of shifting the balance between excitation and inhibition, with a particular emphasis on the spinal dorsal horn. ⋯ Structural remodeling and reorganization represent another exciting area of advance in our understanding of pain. Here, new insights into maladaptive structural plasticity of spinal synapses and molecular determinants thereof will be discussed. Finally, the role of synapse-to-nucleus communication in mediating long-term changes in nociceptive sensitivity is discussed from the view point of pain chronicity.
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This review presents a general model for the understanding of pain, placebo, and chronification of pain in the framework of cognitive neuroscience. The concept of a computational cost-function underlying the functional imaging responses to placebo manipulations is put forward and demonstrated to be compatible with the placebo literature including data that demonstrate that placebo responses as seen on the behavioural level may be elicited on all levels of the neuroaxis. In the same vein, chronification of pain is discussed as a consequence of brain mechanisms for learning and expectation. ⋯ Women are greatly overrepresented in patients with chronic pain. Hence, both from a general standpoint and from reasons of health equity, it is of essence to advance research and care efforts. Success in these efforts will only be granted with better theoretical concepts of chronic pain mechanisms that maps into the framework of cognitive neuroscience.
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Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. ⋯ Mimicking the nerve injury-induced increase of DRG MZF1 through microinjection of recombinant adeno-associated virus 5 expressing full-length MZF1 into the DRG produced significant mechanical, cold, and thermal pain hypersensitivities in naive rats. Mechanistically, MZF1 participated in CCI-induced reductions in Kv1.2 mRNA and protein and total Kv current and the CCI-induced increase in neuronal excitability through MZF1-triggered Kv1.2 AS RNA expression in the injured DRG neurons. MZF1 is likely an endogenous trigger of neuropathic pain and might serve as a potential target for preventing and treating this disorder.
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Patients with chronic fatigue syndrome (CFS) frequently demonstrate intolerance to physical exertion that is often reported as increased and long-lasting fatigue. Because no specific metabolic alterations have been identified in CFS patients, we hypothesized that sensitized fatigue pathways become activated during exercise corresponding with increased fatigue. After exhausting handgrip exercise, muscle metabolites were trapped in the forearm tissues of 39 CFS patients and 29 normal control (NC) by sudden occlusion for up to 5 minutes. ⋯ Quantitative sensory testing demonstrated heat and mechanical hyperalgesia in CFS subjects. Our findings provide indirect evidence for significant contributions of peripheral tissues to the increased exercise-related fatigue in CFS patients consistent with sensitization of fatigue pathways. Future interventions that reduce sensitization of fatigue pathways in CFS patients may be of therapeutic benefit.