Pain
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The German Research Network on Neuropathic Pain (DFNS) has recommended a protocol with 13 quantitative sensory testing (QST) measures for detecting somatosensory abnormalities. Reliability is an important scientific property and has been adequately tested for cutaneous QST. This study evaluates intraoral sites for which no reliability trials have yet been published. ⋯ For each test, inter- and intra-examiner reliabilities at intra- and extraoral sites were similar. No significant differences between right and left sides were found intraorally. We conclude that inter- and intra-examiner reliabilities of most QST measures are acceptable for assessing somatosensory function in the orofacial region.
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The Emotional Controls of Nociception (ECON) paradigm involves the presentation of emotionally-charged pictures during which painful stimuli are delivered. Across several ECON studies, unpleasant pictures enhanced pain and nociception, whereas pleasant pictures inhibited pain and nociception. However, at this time it is unknown whether emotional valence (unpleasant, neutral, pleasant) influences the habituation or sensitization of pain responses that occurs within a testing session. ⋯ Mixed effects ANOVAs verified that within-subject changes in pain responses were influenced by stimulus repetition (NFR and SCR habituated, pain ratings sensitized) and emotional valence (responses were highest during unpleasant pictures, intermediate during neutral pictures, and lowest during pleasant pictures). However, habituation/sensitization slopes were unaffected by emotional valence, thus indicating emotional valence modulation was consistently observed throughout the testing session. These results provide additional validation for the ECON paradigm and suggest that the circuit responsible for emotional modulation of pain and nociception is less susceptible to habituation or sensitization than the circuits responsible for responses to suprathreshold shocks.
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Previous studies suggested that areas of the pain matrix of the human brain are recruited by the processing of pain-related environmental cues such as pain-related pictures or descriptors of pain. However, it is still sketchy whether those activations are specific to the pain-relevance of the stimuli or simply reflect a general effect of negative valence or increased arousal. The present study investigates the neural mechanisms underlying the processing of pain-related, negative, positive, and neutral words. ⋯ However, when attention was focused on a foreground task and words were presented in the background (distraction task), we found a decrease in activation within dorsal anterior cingulum (dACC) and a relative increase in activation within the subgenual ventral anterior cingulum (sACC) when processing pain related words compared to other words. Thus, activations to pain-related words are strongly modulated by the attention demands of the task. Most remarkably, the differences in processing pain-related words compared to non-pain-related words are specific to the pain-relevance of the words and cannot simply be explained by their valence or arousal.
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Activation of the complement system by injury increases inflammation by producing complement fragments C5a and C3a which are able to recruit and activate immune cells. Complement activation may contribute to pain after inflammation and injury. In this study, we examined whether C5a and C3a elicit nociception when injected into mouse hind paws in vivo, and whether C5a and C3a activate and/or sensitize mechanosensitive nociceptors when applied on peripheral terminals in vitro. ⋯ The presence of C5aR mRNA was detected in DRG. C5a and C3a application elevated [Ca(2+)](i) and facilitated capsaicin-induced [Ca(2+)](i) responses in DRG neurons. The results suggest a potential role for complement fragments C5a and C3a in nociception by activating and sensitizing cutaneous nociceptors.
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Following peripheral inflammation, NMDA receptor (NMDAR) activation in spinal cord dorsal horn neurons facilitates the generation of pain in response to low threshold inputs (allodynia) and signals the phosphorylation of protein kinase C (pPKC) and extracellular signal-regulated kinase 2 (pERK2). Intraplantar complete Freund's adjuvant (CFA) induces inflammatory nociception (allodynic pain) at 24 hours (h) with a concurrent increase in neuronal pPKCgamma and pERK2 but not glial pERK2. These effects are attenuated in a spatial knockout of the NMDAR (NR1 KO) confined to SCDH neurons. ⋯ Deletion of NMDAR-dependent signaling in neurons protects against early CFA-induced allodynia. Subsequent NMDAR-independent signaling that involves neuronal expression of pPKCgamma and the induction of pERK2 and IL-1beta in activated astrocytes contributes to the emergence of NMDAR-independent inflammatory pain behavior at 96h after CFA. Effective reduction of the initiation and maintenance of inflammatory pain requires targeting the neuron-astrocyte-cytokine interactions revealed in these studies.