Tuesday, August 21, 2012

Genetic Basis for Pain

The discovery of human genome allows comparing variations at the genetic level with inter-individual differences in pain thresholds and pain perception. Most studies in the past have focused on genetic polymorphisms that might be responsible for inter-individual differences in pain perception. Recently, genetic studies in families by James Cox and his team members, demonstrating recessively inherited CIP have identified nonsense mutations which result in truncation of the voltage-gated sodium channel type 1 x α subunit (SCN9A) — a 113.5 kb gene comprising 26 exons. The encoded sodium channel is composed of 1977 amino acids and is organised into 4 domains, each with 6 transmembrane segments. [Klugbauer et al. 1995]. The SCNA family of sodium channels (SCN1A-SCN11A) evolved from an archetypal potassium channel by quadruplicating, where 4 potassium subunits have to coalesce to form the functional potassium channel. SCN9A is predominantly expressed in the ‘dorsal root ganglion (DRG) neurons’ and sympathetic ganglion neurons. Functional studies, though performed for only some mutations to date, have shown that CIP associated mutations led to loss of function of Nav1.7.
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