Pain
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Sensitization of the transient receptor potential ion channel vanilloid 1 (TRPV1) is critically involved in inflammatory pain. To date, manifold signaling cascades have been shown to converge onto TRPV1 and enhance its sensitization. However, many of them also play a role for nociceptive pain, which limits their utility as targets for therapeutic intervention. ⋯ Alongside, we identify numerous novel and pain state-dependent binding partners of native TRPV1 in dorsal root ganglia. These data represent a unique resource on the dynamics of the TRPV1 interactome and facilitate mechanistic insights into TRPV1 regulation. We propose that inflammation-related differences in the TRPV1 interactome identified here could be exploited to specifically target inflammatory pain in the future.
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Dorsal root ganglion (DRG) neurons provide connectivity between peripheral tissues and the spinal cord. Transcriptional plasticity within DRG sensory neurons after peripheral nerve injury contributes to nerve repair but also leads to maladaptive plasticity, including the development of neuropathic pain. This study presents tissue and neuron-specific expression profiling of both known and novel long noncoding RNAs (LncRNAs) in the rodent DRG after nerve injury. ⋯ This resource is publicly available and will aid future studies of DRG neuron identity and the transcriptional landscape in both the naive and injured DRG. We present our work regarding novel antisense and intergenic LncRNAs as an online searchable database, accessible from PainNetworks (http://www.painnetworks.org/). We have also integrated all annotated gene expression data in PainNetworks, so they can be examined in the context of their protein interactions.
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Multicenter Study
PRISM: a brief screening tool to identify risk in parents of youth with chronic pain.
Having a child with chronic pain impacts a parent's life. Reciprocally, parent cognitive, affective, and behavioral responses to the child's chronic pain can influence the child's pain experience. The purpose of this study is to develop a brief self-report screening tool (Parent Risk and Impact Screening Measure [PRISM]) of parent psychosocial functioning and behavioral responses to child pain. ⋯ Cutoff scores were determined to identify parents at differing levels of risk. The PRISM is a brief and clinically important means of screening parent distress and behaviors associated with child pain-related dysfunction. Further validation will use PRISM in longitudinal studies, particularly testing PRISM scores as a predictor of parent and child outcomes over time.
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Joint inflammation is present in a subpopulation of knee osteoarthritis (OA) patients. Proinflammatory cytokines are known to sensitize the peripheral and central pain pathways. This can be mechanistically assessed by pressure pain thresholds and temporal summation of pain (TSP). ⋯ In conclusion, this study found that mechanistic pain profiling can predict pain alleviation of NSAIDs and paracetamol. Facilitated TSP and low clinical pain scores before treatment are independent predictors of poor pain alleviation after NSAIDs and paracetamol. This study adds to the growing evidence that a subgroup of knee OA patients with manifested central sensitization may require special management attention.
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Pain is associated with negative emotions such as anxiety, but the underlying neurocircuitry and modulators of the association of pain and anxiety remain unclear. The neuropeptide cholecystokinin (CCK) has both pronociceptive and anxiogenic properties, so we explored the role of CCK in anxiety and nociception in the central amygdala (CeA), a key area in control of emotions and descending pain pathways. Local infusion of CCK into the CeA of control rats increased anxiety, as measured in the light-dark box test, but had no effect on mechanical sensitivity. ⋯ This analgesic effect was likely mediated by identified CeA neurons projecting to the periaqueductal gray matter that express CCK receptors. Together, our data demonstrate that intra-CeA CCK infusion activated a descending CCK2 receptor-dependent pathway that inhibited spinal neuron discharge. Thus, persistent pain induces a functional switch to a newly identified analgesic capacity of CCK in the amygdala, indicating central emotion-related circuit controls pain transmission in spinal cord.