Pain
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The exchange proteins activated by cAMP (Epacs) have been shown to play important roles in producing inflammation-induced nociception. Transient receptor potential vanilloid type 1 (TRPV1) is a major receptor processing thermal and chemosensitive nociceptive information. The role of Epacs in modulating the activity of TRPV1 has yet to be determined. ⋯ In addition, CPT increased the expression of phosphorylated PKCα (pPKCα) and membrane TRPV1 expression in DRG. Studying the colocalization of TRPV1 and pPKCα or pPKCε in DRG slices prepared from CFA-treated rats, we found that pPKCα or pPKCε expressed with TRPV1 in different-sized neurons to exert differential influences on TRPV1 activity. Thus, Epac-PKC signaling is critically important in producing inflammation-induced potentiation of TRPV1 functions.
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Pain is a prevalent and debilitating symptom of multiple sclerosis (MS); yet, the mechanisms underlying this pain are unknown. Previous studies have found that the functional relationships between the salience network (SN), specifically the right temporoparietal junction a SN node, and other components of the dynamic pain connectome (default mode network [DMN], ascending and descending pathways) are abnormal in many chronic pain conditions. ⋯ We found that (1) ∼50% of our patients had NP features, (2) abnormalities in SN-DMN sFC were driven by the mixed-neuropathic subgroup, (3) in patients with mixed NP, dFC measures showed that there was a striking change in how the SN was engaged with the ascending nociceptive pathway and descending modulation pathway, (4) BOLD variability was increased in the DMN, and (5) the degrees of sFC and BOLD variability abnormalities were related to pain interference. We propose that abnormal SN-DMN cross-network FC and temporal dynamics within and between regions of the dynamic pain connectome reflect MS pain features.
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The dorsal horn of the spinal cord (laminae I-VI) processes diverse modalities of nociceptive and nonnociceptive sensory information. Antenna-type neurons with cell bodies located in lamina III and large dendritic trees extending from the superficial lamina I to deep lamina IV are best shaped for the integration of a wide variety of inputs arising from primary afferent fibers and intrinsic spinal circuitries. Although the somatodendritic morphology, the hallmark of antenna neurons, has been well studied, little is still known about the axon structure and basic physiological properties of these cells. ⋯ The neurons received monosynaptic inputs from the low-threshold Aβ afferents, Aδ afferents, as well as from the high-threshold Aδ, and C afferents. When selectively activated, C-fiber-driven monosynaptic and polysynaptic excitatory postsynaptic potentials were sufficiently strong to evoke firing in the neurons. Thus, lamina III antenna neurons integrate low-threshold and nociceptive high-threshold primary afferent inputs and can function as wide dynamic range neurons able to directly connect deep dorsal horn with the major nociceptive projection area lamina I.
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Randomized Controlled Trial
Efficacy of adding interoceptive exposure to intensive interdisciplinary treatment for adolescents with chronic pain: a randomized controlled trial.
Fear of pain plays an important role in the maintenance of chronic pain. It may be reduced through exposure therapy. This 2-arm parallel samples randomized controlled trial aimed to investigate whether interoceptive exposure (IE) therapy enhances reductions in fear of pain (primary outcome), pain (pain intensity, pain-related disability, and school absence), and emotional characteristics (anxiety and catastrophizing) when implemented as an adjunctive treatment in the context of intensive interdisciplinary pain treatment for pediatric chronic pain patients. ⋯ There were no greater decreases in the IE group (P > 0.1). The exploratory analyses revealed that the patients with high fear of pain before treatment (P < 0.05, (Equation is included in full-text article.)> 0.03) and the patients with abdominal pain (P < 0.04, (Equation is included in full-text article.)> 0.25) showed greater decreases in their fear of pain (total and subscale score) in the IE group than in the RT group. In conclusion, the results suggest that IE is not particularly effective for all the pediatric chronic pain patients, but the patients with high fear of pain before treatment and with abdominal pain strongly benefit from this intervention.