Pain
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Pain experience can change the central processing of nociceptive inputs, resulting in persistent allodynia and hyperalgesia. However, the underlying circuit mechanisms remain underexplored. Here, we focus on pain-induced remodeling of the projection from the mediodorsal thalamus (MD) to the anterior cingulate cortex (ACC), a projection that relays spinal nociceptive input for central processing. ⋯ After prolonged (∼30 days) CCI, injury-generated silent synapses declined to low levels, which likely resulted from a synaptic maturation process that strengthens AMPAR-mediated MD-to-ACC transmission. Consistent with this hypothesis, viral-mediated knockdown of GluN2B in ACC neurons, which prevented pain-induced generation of silent synapses and silent synapse-mediated strengthening of MD-to-ACC projection after prolonged CCI, prevented the development of allodynia. Taken together, our results depict a silent synapse-mediated mechanism through which key supraspinal neural circuits that regulate pain sensitivity are remodeled to induce allodynia and hyperalgesia.
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Multicenter Study
Hippocampus shape deformation: potential diagnostic biomarker for chronic back pain in women.
Sex differences in the quality and prevalence of chronic pain are manifold, with women generally presenting higher incidence and severity. Uncovering chronic pain-related sex differences inform neural mechanisms and may lead to novel treatment routes. In a multicenter morphological study (total n = 374), we investigated whether the shape of subcortical regions would reflect sex differences in back pain. ⋯ Weeks after onset of back pain, there was no deformation within alHP, but at 1 and 3 years women exhibited a trend for outer deformation. The alHP partly overlapped with the subiculum and entorhinal cortex, whose functional connectivity, in healthy subjects, was associated with emotional and episodic memory related terms (Neurosynth, reverse inference). These findings suggest that in women the alHP undergoes anatomical changes with pain persistence, highlighting sexually dimorphic involvement of emotional and episodic memory-related circuitry with chronic pain.
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Persistent idiopathic facial pain (PIFP) is a poorly understood chronic pain syndrome of the face, formerly known as atypical facial pain. It is characterized by a constant painful sensation without neurological abnormalities and without clinically objectifiable cause. Similarities to neuropathic pain conditions have been discussed and are currently thought to be relevant for the pathophysiology of this disease. ⋯ Patients with PIFP show exclusively a stronger activation to painful stimulation in the spinal trigeminal nucleus when contrasted against healthy controls. Our data suggest that abnormal central pain processing plays a role in the pathophysiology of PIFP. An integration of these findings into neuropathic pain models might help to gain a better general understanding of the pathophysiology of PIFP.
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Fibromyalgia (FM) is characterized by widespread chronic pain, fatigue, and somatic symptoms. The influence of phenotypic changes in monocytes on symptoms associated with FM is not fully understood. The primary aim of this study was to take a comprehensive whole-body to molecular approach in characterizing relationships between monocyte phenotype and FM symptoms in relevant clinical populations. ⋯ Taken together, our data suggest that monocyte phenotype and their cytokine profiles are associated with pain-related symptoms in individuals with FM. Furthermore, our data show that IL-5 has a potential role in analgesia in an animal model of FM. Thus, targeting anti-inflammatory cytokines such as IL-5 secreted by circulating leukocytes could serve as a promising intervention to control pain and other somatic symptoms associated with FM.
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Diabetes is a leading cause of peripheral neuropathy (diabetic peripheral neuropathy, DPN), and uncontrolled long-lasting hyperglycemia leads to severe complications. A major proportion of diabetics develop excruciating pain with a variable course. Mechanisms leading to painful DPN are not completely understood and treatment options limited. ⋯ Our analyses identify miR-33 and miR-380 expressed in nociceptive neurons as critical denominators of diabetic pain and miR-124-1 as a mediator of physiological nociception. Our comprehensive analyses on the putative mRNA targets for miR-33 or miR-124-1 identified a set of mRNAs that are regulated after miR-33 or miR-124-1 overexpression in dorsal root ganglia in vivo. Our results shed light on the regulation of DPN pathophysiology and implicate specific miRNAs as novel therapeutic targets for treating painful DPN.