{"owner": "ArrayExpress Uploader", "pop_total": 0, "species": "mouse", "factors": [{"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM150328": {"GENOTYPE": "Nav1.7 KO"}}, {"GSM150328": {"GENOTYPE": "Nav1.7 KO"}}, {"GSM150328": {"GENOTYPE": "Nav1.7 KO"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503287": {"GENOTYPE": "Nav1.8 KO"}}, {"GSM1503287": {"GENOTYPE": "Nav1.8 KO"}}, {"GSM1503287": {"GENOTYPE": "Nav1.8 KO"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503278": {"GENOTYPE": "Wild Type"}}, {"GSM1503293": {"GENOTYPE": "Nav1.9 KO"}}, {"GSM1503293": {"GENOTYPE": "Nav1.9 KO"}}, {"GSM1503293": {"GENOTYPE": "Nav1.9 KO"}}], "id": 7712, "ownerprofile_id": "arrayexpress_sid", "platform": 6, "summary_wrapped": "Loss of function mutations in the SCN9a gene encoding voltage-gated  sodium channel Nav1.7 cause congenital insensitivity to pain  (CIP)...", "geo_gse_id": "E-GEOD-61373", "owner_profile": "/profile/8773/arrayexpressuploader", "factor_count": 1, "sample_count": 18, "tags": ["analgesia", "congenital insensitivity to pain", "dorsal", "dorsal root", "enkephalin", "genome", "neuron", "peripheral", "protein", "sensory neuron", "spinal cord"], "lastmodified": "Dec.12, 2014", "is_default": false, "geo_id_plat": "E-GEOD-61373_A-AFFY-45", "slug": "the-molecular-basis-of-analgesia-in-congenital-ins", "geo_gds_id": "", "name": "The molecular basis of analgesia in congenital insensitivity to pain associated with loss of Nav1.7 function", "created": "Nov.12, 2014", "summary": "Loss of function mutations in the SCN9a gene encoding voltage-gated  sodium channel Nav1.7 cause congenital insensitivity to pain  (CIP)  and anosmia in otherwise normal humans and mice, suggesting that this channel may be a good analgesic drug  target.  Surprisingly, potent selective antagonists of Nav1.7 are weak analgesics.  We therefore investigated whether Nav1.7 , as well as contributing to electrical signalling  may have  an additional function.     Here we report  that Nav1.7 deletion has profound effects on the sensory neuron transcriptome, leading to dysregulation  of a number of transcription factors  as well as upregulation of enkephalin precursor PENK mRNA and down regulation of CEACAM10 mRNA, a protein involved in noxious thermosensation.   PENK mRNA is transcriptionally upregulated in Nav1.7 null mutant female sensory neurons, resulting in increased enkephalin expression  in the dorsal horn of the spinal cord.   PENK expression is down-regulated  by addition of the sodium ionophore monensin, suggesting that sodium may play a role as a second messenger. Application of the opioid antagonist naloxone strongly enhances noxious peripheral input into the spinal cord,   and dramatically reduces analgesia in both male and female Nav1.7 null mutant mice, as well as in human Nav1.7 null mutants.  These data show that loss of Nav1.7 expression increases opioid drive over the lifetime of  mice and humans. They further suggest that  Nav1.7 channel blockers alone may not replicate the phenotype of null mutant humans and mice, but should be potentiated with exogenous opioids. RNA was extracted from Dorsal Root Ganglia tissue from Nav1.7 Knock-Out, Nav1.8 KO and Nav1.9 KO mice (n = 3) and hybridised on Affymetrix Mouse Genome 430 2.0 Array (GPL1261)", "source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-61373", "sample_source": "http://www.ebi.ac.uk/arrayexpress/experiments/E-GEOD-61373/samples/"}