Mol Pain
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Mitochondria are important organelles functioning in metabolic processes, inflammatory response and neurological disorders. Migraines are chronic and paroxysmal neurological disorders characterized by recurrent episodes of severe headache and other neurological symptoms. We explored whether mitochondria may be genetically and/or causally associated with migraine. ⋯ This study indicates fresh evidence of association between mtDNA-CN, mitochondrial related exposures and migraine especially migraine without aura. The findings may shed light on developing interventions targeting on the causal pathway from mitochondria to migraine.
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The anterior cingulate cortex (ACC) is critical for pain perception, emotion and cognition. Previous studies showed that the ACC has a complex network architecture, which can receive some projection fibers from many brain regions, including the thalamus, the cerebral cortex and other brain regions. However, there was still a lack of whole-brain mapping of the ACC in adult mice. ⋯ We also found that cortical neurons in the ACC mainly receive ipsilateral monosynaptic projections. Some cortical areas and forebrain regions also bilaterally projected to the ACC. These findings provide a complete analysis of the afferents to the ACC in adult mice, and whole-brain mapping of ACC afferents would provide important anatomic evidence for the study of pain, memory, and cognition.
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Activation of neurons and glial cells in the dorsal root ganglion is one of the key mechanisms for the development of hyperalgesia. The aim of the present study was to examine the role of neuroglial activity in the development of opioid-induced hyperalgesia. Male rats were treated with morphine daily for 3 days. ⋯ Morphine activates ERK1/2 in neurons and satellite glial cells in the dorsal root ganglion via the opioid receptor and toll like receptor-4. ERK1/2 phosphorylation is gap junction-dependent and is associated with the alteration of cytokine expression. Inhibition of neuroinflammation by activation of neurons and glia might be a promising target to prevent opioid-induced hyperalgesia.
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Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to contribute to neuropathic pain via astrocyte-microglial interaction in the spinal cord. Whether CCL7 in the trigeminal ganglion (TG) involves in trigeminal neuropathic pain and the involved mechanism remain largely unknown. ⋯ CCL7 activates ERK in TG neurons via CCR2 and CCR3 to enhance neuronal excitability, which contributes to the maintenance of trigeminal neuropathic pain. CCL7-CCR2/CCR3-ERK pathway may be potential targets for treating trigeminal neuropathic pain.
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Chronic pain is one of the most common, costly, and potentially debilitating health issues facing older adults, with attributable costs exceeding $600 billion annually. The prevalence of pain in humans increases with advancing age. Yet, the contributions of sex differences, age-related chronic inflammation, and changes in neuroplasticity to the overall experience of pain are less clear, given that opposing processes in aging interact. ⋯ We provide evidence to suggest that neurodegenerative conditions engender a loss of neural plasticity involved in pain response, whereas low-grade inflammation in aging increases CNS sensitization but decreases PNS sensitivity. Insights from preclinical studies are needed to answer mechanistic questions. However, the selection of appropriate aging models presents a challenge that has resulted in conflicting data regarding pain processing and behavioral outcomes that are difficult to translate to humans.