Disease relevance of SCN10A

• We report that nerve injury depress levels of SCN10A-specific mRNA in contralateral as well as ipsilateral dorsal root ganglia of rats, suggesting a possible peripheral mechanism for the contralateral 'mirror-image' hyperalgesia described in nerve-injured humans and experimental animals [1].
• Our studies suggest that the best target for SNS/PN3 blocking agents is likely to be chronic local hypersensitivity [2].
• While further studies are required, these findings suggest that accumulation of SNS/PN3 and/or loss of GDNF may contribute to pain in causalgia, and that selective blockers of SNS/PN3 and/or rhGDNF may provide effective novel treatments [3].
• FINDINGS: Both subtypes of sodium channels PN1 and PN3 accumulated abnormally in human neuromas [4].
• Selective SNS/PN3- and NaN/SNS2-blocking agents may provide new therapy for back pain and sciatica [5].

High impact information on SCN10A

• Three novel targets have received much attention recently: N-methyl-D-aspartate receptor subtypes such as the glycine and NR2B sites, and the tetrodotoxin-resistant voltage-gated sodium channel (Na(v) 1.8; SNS/PN3) [6].
• Immunolocalization of SNS/PN3 and NaN/SNS2 sodium channels in human pain states [2].
• In brachial plexus injury patients, there was an acute decrease of SNS/PN3- and NaN/SNS2-like immunoreactivity in sensory cell bodies of cervical dorsal root ganglia (DRG) whose central axons had been avulsed from spinal cord, with gradual return of the immunoreactivity to control levels over months [2].
• Using specific antibodies, we have studied, for the first time in humans, the presence of SNS/PN3 and NaN/SNS2 in peripheral nerves, including tissues from patients with chronic neurogenic pain [2].
• There is a dramatic change in sodium channel expression in DRG neurons, with down-regulation of the SNS/PN3 and NaN sodium channel genes and up-regulation of previously silent Type III sodium channel gene, following injury to the axons of these cells [7].

Biological context of SCN10A

• SCN11A is localized to human chromosome 3 (3p21-24) close to the other TTX-R sodium channel genes SCN5A and SCN10A [8].
• The sodium channel genes SCN5A, SCN10A, and SCN12A on chromosome 3 were excluded as candidates (LOD scores < or =-2) [9].
• The homologous relationship between rPN3 and hPN3 is defined by (i) a high level of sequence identity (ii) sodium currents that are highly resistant to tetrodotoxin (TTX) (iii) similar tissue distribution profiles and (iv) orthologous chromosomal map positions [10].
• The amino acid sequence of hPN3 is most closely related to the rat PN3/SNS sodium channels which are expressed primarily in the small neurons of rat DRGs [10].
• The human PN3 channel expressed in stable transfectants showed TTX-resistant inward currents with slow inactivation kinetics [11].

Anatomical context of SCN10A

• A tetrodotoxin-resistant voltage-gated sodium channel from human dorsal root ganglia, hPN3/SCN10A [10].
• Expression of hPN3 in Xenopus oocytes showed that this clone is a functional voltage-gated sodium channel [10].
• The tetrodotoxin-resistant (TTX-R) voltage-gated sodium channel SNS/PN3 and the newly discovered NaN/SNS2 are expressed in sensory neurones, particularly in nociceptors [2].
• The expected fully mature 260 kDa component of SNS/PN3 was noted in all injured nerve tissues obtained from adults; however, for SNS2/NaN, smaller bands were found, most likely arising from protein degradation [12].
• We generated recombinant cell lines stably expressing the human PN1 and PN3 sodium channels in Chinese hamster ovary (CHO) cells using inducible expression vectors [11].

Other interactions of SCN10A

• Stable expression and characterization of human PN1 and PN3 sodium channels [11].

Analytical, diagnostic and therapeutic context of SCN10A

• Accumulation of PN1 and PN3 sodium channels in painful human neuroma-evidence from immunocytochemistry [4].

References