Dataset Information

Global Gene Knockout of Kcnip3 Enhances Pain Sensitivity and Exacerbates Negative Emotions in Rats.

ABSTRACT: The Ca2+-binding protein Kv channel interacting protein 3 (KChIP3) or downstream regulatory element antagonist modulator (DREAM), a member of the neuronal calcium sensor (NCS) family, shows remarkable multifunctional properties. It acts as a transcriptional repressor in the nucleus and a modulator of ion channels or receptors, such as Kv4, NMDA receptors and TRPV1 channels on the cytomembrane. Previous studies of Kcnip3 -/- mice have indicated that KChIP3 facilitates pain hypersensitivity by repressing Pdyn expression in the spinal cord. Conversely, studies from transgenic daDREAM (dominant active DREAM) mice indicated that KChIP3 contributes to analgesia by repressing Bdnf expression and attenuating the development of central sensitization. To further determine the role of KChIP3 in pain transmission and its possible involvement in emotional processing, we assessed the pain sensitivity and negative emotional behaviors of Kcnip3 -/- rats. The knockout rats showed higher pain sensitivity compared to the wild-type rats both in the acute nociceptive pain model and in the late phase (i.e., 2, 4 and 6 days post complete Freund's adjuvant injection) of the chronic inflammatory pain model. Importantly, Kcnip3 -/- rats displayed stronger aversion to the pain-associated compartment, higher anxiety level and aggravated depression-like behavior. Furthermore, RNA-Seq transcriptional profiling of the forebrain cortex were compared between wild-type and Kcnip3 -/- rats. Among the 68 upregulated genes, 19 genes (including Nr4a2, Ret, Cplx3, Rgs9, and Itgad) are associated with neural development or synaptic transmission, particularly dopamine neurotransmission. Among the 79 downregulated genes, 16 genes (including Col3a1, Itm2a, Pcdhb3, Pcdhb22, Pcdhb20, Ddc, and Sncaip) are associated with neural development or dopaminergic transmission. Transcriptional upregulation of Nr4a2, Ret, Cplx3 and Rgs9, and downregulation of Col3a1, Itm2a, Pcdhb3 and Ddc, were validated by qPCR analysis. In summary, our studies showed that Kcnip3 -/- rats displayed higher pain sensitivity and stronger negative emotions, suggesting an involvement of KChIP3 in negative emotions and possible role in central nociceptive processing.

SUBMITTER: Guo YP

PROVIDER: S-EPMC6355686 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Global Gene Knockout of Kcnip3 Enhances Pain Sensitivity and Exacerbates Negative Emotions in Rats.

Guo Yu-Peng YP Zhi Yu-Ru YR Liu Ting-Ting TT Wang Yun Y Zhang Ying Y

Frontiers in molecular neuroscience 20190125

The Ca2+-binding protein Kv channel interacting protein 3 (KChIP3) or downstream regulatory element antagonist modulator (DREAM), a member of the neuronal calcium sensor (NCS) family, shows remarkable multifunctional properties. It acts as a transcriptional repressor in the nucleus and a modulator of ion channels or receptors, such as Kv4, NMDA receptors and TRPV1 channels on the cytomembrane. Previous studies of Kcnip3 -/- mice have indicated that KChIP3 facilitates ...[more]

PMID: 30740043

Similar Datasets

Project description:ObjectiveOpioids are frequently prescribed for chronic low back pain (CLBP), but there are broad individual differences in the benefits and risks of opioid therapy, including the development opioid-induced hyperalgesia. This study examined quantitative sensory testing (QST) data among a group of CLBP patients undergoing sustained oral opioid treatment. We investigated whether individual differences in psychological characteristics were related to opioid-induced changes in pain perception and pain modulation.DesignThe six-month, open-label trial evaluated patients with low to high levels of negative affect (e.g., symptoms of distress, depression and anxiety); participants underwent QST at baseline (prior to initiating treatment) and during oral opioid treatment.SettingA chronic pain management center.PatientsThe 31 study participants had chronic discogenic back pain, with a pain intensity rating >3/10. Participants were divided into groups with high vs. low levels of Negative Affect (NA).ResultsIn the previously-published manuscript describing the clinical outcomes of the trial, high NA patients achieved only about half of the analgesic effect observed in the low NA group (Wasan AD, Michna E, Edwards RR, et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology 2015;123:861-72). The QST findings reported here suggested that tolerance to experimental (cold pressor) pain and conditioned pain modulation tended to decrease in the high NA group over the course of opioid treatment, while temporal summation of mechanical pain declined in the low NA group.ConclusionsThese results reveal that while the low NA group seemed to exhibit a generally adaptive, analgesic pattern of changes during opioid management, the high NA group showed a pattern more consistent with opioid-induced hyperalgesic processes. A greater susceptibility to hyperalgesia-promoting changes in pain modulation among patients with high levels of distress may contribute to a lower degree of benefit from opioid treatment in high NA patients.

Project description:Until recently, research in animal welfare science has mainly focused on negative experiences like pain and suffering, often neglecting the importance of assessing and promoting positive experiences. In rodents, specific facial expressions have been found to occur in situations thought to induce negatively valenced emotional states (e.g., pain, aggression and fear), but none have yet been identified for positive states. Thus, this study aimed to investigate if facial expressions indicative of positive emotional state are exhibited in rats. Adolescent male Lister Hooded rats (Rattus norvegicus, N = 15) were individually subjected to a Positive and a mildly aversive Contrast Treatment over two consecutive days in order to induce contrasting emotional states and to detect differences in facial expression. The Positive Treatment consisted of playful manual tickling administered by the experimenter, while the Contrast Treatment consisted of exposure to a novel test room with intermittent bursts of white noise. The number of positive ultrasonic vocalisations was greater in the Positive Treatment compared to the Contrast Treatment, indicating the experience of differentially valenced states in the two treatments. The main findings were that Ear Colour became significantly pinker and Ear Angle was wider (ears more relaxed) in the Positive Treatment compared to the Contrast Treatment. All other quantitative and qualitative measures of facial expression, which included Eyeball height to width Ratio, Eyebrow height to width Ratio, Eyebrow Angle, visibility of the Nictitating Membrane, and the established Rat Grimace Scale, did not show differences between treatments. This study contributes to the exploration of positive emotional states, and thus good welfare, in rats as it identified the first facial indicators of positive emotions following a positive heterospecific play treatment. Furthermore, it provides improvements to the photography technique and image analysis for the detection of fine differences in facial expression, and also adds to the refinement of the tickling procedure.

Dataset Information

Global Gene Knockout of Kcnip3 Enhances Pain Sensitivity and Exacerbates Negative Emotions in Rats.

Publications

Global Gene Knockout of <i>Kcnip3</i> Enhances Pain Sensitivity and Exacerbates Negative Emotions in Rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets