RGD Reference Report - Reopening of ATP-sensitive potassium channels reduces neuropathic pain and regulates astroglial gap junctions in the rat spinal cord. - Rat Genome Database

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Reopening of ATP-sensitive potassium channels reduces neuropathic pain and regulates astroglial gap junctions in the rat spinal cord.

Authors: Wu, Xue-Feng  Liu, Wen-Tao  Liu, Yue-Peng  Huang, Zhi-Jiang  Zhang, Yan-Kai  Song, Xue-Jun 
Citation: Wu XF, etal., Pain. 2011 Nov;152(11):2605-15. doi: 10.1016/j.pain.2011.08.003. Epub 2011 Sep 9.
RGD ID: 12791994
Pubmed: PMID:21907492   (View Abstract at PubMed)
DOI: DOI:10.1016/j.pain.2011.08.003   (Journal Full-text)

Adenosine triphosphate-sensitive potassium (K(ATP)) channels are suggested to be involved in pathogenesis of neuropathic pain, but remain underinvestigated in primary afferents and in the spinal cord. We examined alterations of K(ATP) channels in rat spinal cord and tested whether and how they could contribute to neuropathic pain. The results showed that protein expression for K(ATP) channel subunits SUR1, SUR2, and Kir6.1, but not Kir6.2, were significantly downregulated and associated with thermal hyperalgesia and mechanical allodynia after sciatic nerve injury. Spinal administration of a K(ATP) channel opener cromakalim (CRO, 5, 10, and 20 µg, respectively) prevented or suppressed, in a dose-dependent manner, the hyperalgesia and allodynia. Nerve injury also significantly increased expression and phosphorylation of connexin 43, an astroglial gap junction protein. Such an increase of phosphorylation of connexin 43 was inhibited by CRO treatment. Furthermore, preadministration of an astroglial gap junction decoupler carbenoxolone (10 µg) completely reversed the inhibitory effects of CRO treatment on the hyperalgesia and allodynia and phosphorylation of NR1 and NR2B receptors and the subsequent activation of Ca(2+)-dependent signals Ca(2+)/calmodulin-dependent kinase II and cyclic adenosine monophosphate (cAMP) response element binding protein. These findings suggest that nerve injury-induced downregulation of the K(ATP) channels in the spinal cord may interrupt the astroglial gap junctional function and contribute to neuropathic pain, thus the K(ATP) channels opener can reduce neuropathic pain probably partly via regulating the astroglial gap junctions. This study may provide a new strategy for treating neuropathic pain using K(ATP) channel openers in the clinic.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sciatic neuropathy  ISOAbcc8 (Rattus norvegicus)12791994; 12791994protein:decreased expression:spinal cordRGD 
sciatic neuropathy  ISOAbcc9 (Rattus norvegicus)12791994; 12791994protein:decreased expression:spinal cordRGD 
sciatic neuropathy  IEP 12791994; 12791994; 12791994protein:decreased expression:spinal cordRGD 
sciatic neuropathy  ISOKcnj8 (Rattus norvegicus)12791994; 12791994protein:decreased expression:spinal cordRGD 

Objects Annotated

Genes (Rattus norvegicus)
Abcc8  (ATP binding cassette subfamily C member 8)
Abcc9  (ATP binding cassette subfamily C member 9)
Kcnj8  (potassium inwardly-rectifying channel, subfamily J, member 8)

Genes (Mus musculus)
Abcc8  (ATP-binding cassette, sub-family C member 8)
Abcc9  (ATP-binding cassette, sub-family C member 9)
Kcnj8  (potassium inwardly-rectifying channel, subfamily J, member 8)

Genes (Homo sapiens)
ABCC8  (ATP binding cassette subfamily C member 8)
ABCC9  (ATP binding cassette subfamily C member 9)
KCNJ8  (potassium inwardly rectifying channel subfamily J member 8)


Additional Information