Journal
JOURNAL OF NEUROSCIENCE
Volume 27, Issue 24, Pages 6363-6373Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0307-07.2007
Keywords
pain; calcium channels; N-type; splice isoforms; siRNA; dorsal root ganglion
Categories
Funding
- NINDS NIH HHS [R01 NS055251-05, NS055251, R01 NS029967, R01 NS055251, NS29967] Funding Source: Medline
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N-type calcium channels are essential mediators of spinal nociceptive transmission. The core subunit of the N-type channel is encoded by a single gene, and multiple N-type channel isoforms can be generated by alternate splicing. In particular, cell-specific inclusion of an alternatively spliced exon 37a generates a novel form of the N-type channel that is highly enriched in nociceptive neurons and, as we show here, downregulated in a neuropathic pain model. Splice isoform-specific small interfering RNA silencing in vivo reveals that channels containing exon 37a are specifically required for mediating basal thermal nociception and for developing thermal and mechanical hyperalgesia during inflammatory and neuropathic pain. In contrast, both N-type channel isoforms (e37a- and e37b-containing) contribute to tactile neuropathic allodynia. Hence, exon 37a acts as a molecular switch that tailors the channels toward specific roles in pain.
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