Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
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Target Concepts:
Gene/Protein
Disease
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Query: UMLS:C0344307 (
analgesia
)
28,200
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Ca
2+
-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.
...
PMID:Global Gene Knockout of
Kcnip3
Enhances Pain Sensitivity and Exacerbates Negative Emotions in Rats. 3074 43
