Neuroscience
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This review addresses the fundamental question of how we first experience pain, at the beginning of our lives. The brain is activated by peripheral tissue damaging stimulation from birth, but unlike other sensory systems, the pain system in healthy individuals cannot rely upon prolonged activity-dependent shaping through repeated noxious stimulation. Considering the importance of pain, remarkably little is known about when and how nociceptive cortical network activity characteristic of the mature adult brain develops. ⋯ Since this developing brain connectome is necessary, if not sufficient, for pain experience, we discuss the structural and functional development of cortical and subcortical networks that contribute to this network. We then review specific information on the development of nociceptive processing in the infant brain, considering evidence from neurophysiological and hemodynamic measures separately, as the two are not always consistent. Finally we highlight areas that require further research and discuss how information gained from laboratory animal models will greatly increase our understanding in this area.
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The midbrain dopamine center comprises a key network for reward, salience, motivation, and mood. Evidence from various clinical and preclinical settings points to the midbrain dopamine circuit as an important modulator of pain perception and pain-induced anxiety and depression. This review summarizes recent findings that shed light to the neuroanatomical, electrophysiological and molecular adaptations that chronic pain conditions promote in the mesolimbic dopamine system. ⋯ Here, we discuss recent findings on the mechanisms involved in the perception of chronic pain, in pain-induced anxiety and depression, as well as in pain-killer addiction vulnerability. Several new studies also show that the mesolimbic dopamine circuit potently modulates responsiveness to opioids and antidepressants used for the treatment of chronic pain. We discuss recent data supporting a role of the brain reward pathway in treatment efficacy and we summarize novel findings on intracellular adaptations in the brain reward circuit under chronic pain states.
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The noradrenergic system is crucial for several activities in the body, including the modulation of pain. As the major producer of noradrenaline (NA) in the central nervous system (CNS), the Locus Coeruleus (LC) is a nucleus that has been studied in several pain conditions, mostly due to its strategic location. ⋯ The main goal of this review is to bring together the data available regarding the noradrenergic system in relation to pain, particularly focusing on the ascending and descending LC projections in different conditions. How such findings influence our understanding of these conditions is also discussed.
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We have witnessed an accelerated growth of photonics technologies in recent years to enable not only monitoring the activity of specific neurons, while animals are performing certain types of behavior, but also testing whether specific cells, circuits, and regions are sufficient or necessary for initiating, maintaining, or altering this or that behavior. Compared to other sensory systems, however, such as the visual or olfactory system, photonics applications in pain research are only beginning to emerge. One reason pain studies have lagged behind is that many of the techniques originally developed cannot be directly implemented to study key relay sites within pain pathways, such as the skin, dorsal root ganglia, spinal cord, and brainstem. ⋯ We review a number of strategies to circumvent these challenges, by delivering light into, and collecting it from the different key sites to unravel how nociceptive signals are encoded at each level of the neuraxis. We conclude with an outlook on novel imaging modalities for label-free chemical detection and opportunities for multimodal interrogation in vivo. While many challenges remain, these advances offer unprecedented opportunities to bridge cellular approaches with context-relevant behavioral testing, an essential step toward improving translation of basic research findings into clinical applications.
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Fibromyalgia is the current term for chronic widespread musculoskeletal pain for which no alternative cause can be identified. The underlying mechanisms, in both human and animal studies, for the continued pain in individuals with fibromyalgia will be explored in this review. There is a substantial amount of support for alterations of central nervous system nociceptive processing in people with fibromyalgia, and that psychological factors such as stress can enhance the pain experience. ⋯ We will explore the data and neurobiology related to the role of the CNS in nociceptive processing, followed by a short review of studies examining potential peripheral nervous system changes and cytokine involvement. We will not only explore the data from human subjects with fibromyalgia but will relate this to findings from animal models of fibromyalgia. We conclude that fibromyalgia and related disorders are heterogenous conditions with a complicated pathobiology with patients falling along a continuum with one end a purely peripherally driven painful condition and the other end of the continuum is when pain is purely centrally driven.