Pain
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Nociplastic pain, a third mechanistic pain descriptor in addition to nociceptive and neuropathic pain, was adopted in 2017 by the International Association for the Study of Pain (IASP). It is defined as "pain that arises from altered nociception" not fully explained by nociceptive or neuropathic pain mechanisms. Peripheral and/or central sensitization, manifesting as allodynia and hyperalgesia, is typically present, although not specific for nociplastic pain. ⋯ A major challenge is to unravel pathophysiological mechanisms driving altered nociception in patients suffering from nociplastic pain. Examples from fibromyalgia would include pathophysiology of the peripheral as well as central nervous system, such as autoreactive antibodies acting at the level of the dorsal root ganglia and aberrant cerebral pain processing, including altered brain network architecture. Understanding pathophysiological mechanisms and their interactions is a prerequisite for the development of diagnostic tests allowing for individualized treatments and development of new strategies for prevention and treatment.
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Despite hundreds of studies demonstrating the involvement of neuron-glia-immune interactions in the establishment and/or maintenance of persistent pain behaviors in animals, the role (or even occurrence) of so-called "neuroinflammation" in human pain has been an object of contention for decades. Here, I present the results of multiple positron emission tomography (PET) studies measuring the levels of the 18 kDa translocator protein (TSPO), a putative neuroimmune marker, in individuals with various pain conditions. ⋯ While the biological and clinical significance of these findings awaits further work, this emerging preclinical literature supports a role of neuron-glia-immune interactions as possible pathophysiological underpinnings of human chronic pain. Gaining a deeper understanding of the role of neuroimmune function in human pain would likely have important practical implications, possibly paving the way for novel interventions.
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Improving health and wellbeing outcomes for people experiencing chronic musculoskeletal pain requires collective efforts across multiple levels of a healthcare ecosystem. System-wide barriers to care equity must however be addressed (eg, lack of co-designed services; overuse of low value care/underuse of high value care; inadequate health workforce; inappropriate funding models; inequitable access to medicines and technologies; inadequate research and innovation). In this narrative review, utilizing a systems' thinking framework, we synthesize novel insights on chronic musculoskeletal pain research contextualized through the lens of this complex, interconnected system, the "pain care ecosystem." We examine the application of systems strengthening research to build capacity across this ecosystem to support equitable person-centred care and healthy ageing across the lifespan. ⋯ This level is connected with health services and health workforce operating to co-design and deliver person-centred care (meso-level), underpinned further upstream by contemporary health and social care systems (macro-level context). We provide emerging evidence for how we, and others, are working towards building ecosystem resilience to support quality musculoskeletal pain care: at the macro-level (eg, informing musculoskeletal policy and health strategy priorities); at the meso-level (eg, service co-design across care settings; health workforce capacity); and downstream, at the micro-level (eg, person-centred care). We outline the mechanisms and methodologies utilized and explain the outcomes, insights and impact of this research, supported by real world examples extending from Australian to global settings.
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Microglia take on an altered morphology during chronic opioid treatment. This morphological change is broadly used to identify the activated microglial state associated with opioid side effects, including tolerance and opioid-induced hyperalgesia (OIH). Microglia display similar morphological responses in the spinal cord after peripheral nerve injury (PNI). ⋯ After PNI, we identify an early proliferative transcriptional event across models that precedes the upregulation of histological markers of microglial activation. However, we found no proliferative transcriptional response associated with opioid-induced microglial activation, consistent with histological data, indicating that the number of microglia remains stable during morphine treatment, whereas their morphological response differs from PNI models. Collectively, these results establish the diversity of pain-associated microglial transcriptomic responses and point towards the targeting of distinct insult-specific microglial responses to treat OIH, PNI, or other central nervous system pathologies.