Table 2.

Neurotrophic factors: Human mutations and single nucleotide polymorphisms (SNP) associated with altered pain sensitivity.

Neurotrophic factor	Mutation(s) reported	SNP(s) reported	Phenotype	Reference
NGF Encoding NGF	Point mutation located on chromosome 1p11.2-p13.2, resulting in R100W missense mutation in mature NGF		Severe reduction of unmyelinated fibers and congenital insensitivity to pain	Einarsdottir 2004; Minde 2009
NTRK1 Encoding TrkA	Autosomal recessive loss of function mutations		Congenital insensitivity to pain with anhydrosis (CIPA)	Indo 1996
		nonsynonymous SNP NTRK1H604Y, with substitution of tyrosine for histidine	Children with the SNP experienced more post-surgical pain (subtle effect)	Mamie 2013
NGFR Encoding Low Affinity Neurotrophin Receptor P75NTR		rs9908234, but did not replicate in independent cohorts	Genome-wide association study on migraine	Ligthart 2011
BDNF Encoding BDNF		Val66Met	Increased risk for chronic postoperative pain	Tian 2018
	haploinsufficiency of theBDNFgene		Strong reduction in pain sensitivity in patients with Wilms tumor-aniridia (WAGR) syndrome	Sapio 2019