Here we present data gathered by Dr. Jon Berner MD PhD in the course of treatment. Data were collected by Baylor College of Medicine through an untargeted metabolomic analysis with cerebrospinal fluid. Patient data were collected from treatment refractory patients with chronic pain and comorbid psychiatric conditions including: bipolar, depression, and anxiety. Through the use of novel technological methods, Dr. Berner hopes to elucidate underlying metabolic contributors and secondary effects of chronic pain.

Original patient data as gathered by Baylor are published below. Data collection methodology is described in a paper by Miller et al. All z-scores were calculated using an internal database at Baylor representing a large number of reference data (N>300). Data will be presented at the 2021 AAPM Conference, a preliminary abstract is included below.

Patient 1

BIOCHEMICALZ-SCORESUPER_PATHWAYSUB_PATHWAYHMDB_ID
sphingosine3.196182684LipidSphingolipid MetabolismHMDB00252
isocitrate2.293294308EnergyTCA CycleHMDB00193
homoarginine2.169030493Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB00670
creatinine1.912943914Amino AcidCreatine MetabolismHMDB00562
N-acetylleucine1.817411277Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB11756
3-methoxytyramine sulfate1.650947537Amino AcidPhenylalanine and Tyrosine MetabolismNA
phosphate1.624114961EnergyOxidative PhosphorylationHMDB01429
dimethyl sulfone1.610449794XenobioticsChemicalHMDB04983
2-hydroxyadipate1.605101961LipidFatty Acid, DicarboxylateHMDB00321
dehydroepiandrosterone sulfate (DHEA-S)1.569090667LipidSteroidHMDB01032
beta-hydroxyisovalerate1.453610767Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00754
fructose1.451451968CarbohydrateFructose, Mannose and Galactose MetabolismHMDB00660
ribitol1.371657695CarbohydratePentose MetabolismHMDB00508
alpha-hydroxyisocaproate1.358116575Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00746
N-acetylasparagine1.312122328Amino AcidAlanine and Aspartate MetabolismHMDB06028
N-acetylisoleucine1.290683286Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB61684
trigonelline (N’-methylnicotinate)1.286950499Cofactors and VitaminsNicotinate and Nicotinamide MetabolismHMDB00875
urate1.200131614NucleotidePurine Metabolism, (Hypo)Xanthine/Inosine containingHMDB00289
phenylacetylglutamine1.14311539Amino AcidPhenylalanine and Tyrosine MetabolismHMDB06344
3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF)1.126061059LipidFatty Acid, DicarboxylateHMDB61112
androstenediol (3beta,17beta) disulfate (1)1.110590546LipidSteroidHMDB03818
p-cresol sulfate1.08997526Amino AcidPhenylalanine and Tyrosine MetabolismHMDB11635
spermidine1.061191296Amino AcidPolyamine MetabolismHMDB01257
3-hydroxy-2-ethylpropionate1.051809299Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00396
N-acetyl-3-methylhistidine*1.026125258Amino AcidHistidine MetabolismNA
1-methylhistidine0.999860469Amino AcidHistidine MetabolismHMDB00001
nicotinamide riboside0.991475385Cofactors and VitaminsNicotinate and Nicotinamide MetabolismHMDB00855
tryptophan betaine0.981555973Amino AcidTryptophan MetabolismHMDB61115
3-methyl-2-oxobutyrate0.961139634Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00019
imidazole lactate0.955415223Amino AcidHistidine MetabolismHMDB02320
N6-succinyladenosine0.922772344NucleotidePurine Metabolism, Adenine containingHMDB00912
inosine0.918963444NucleotidePurine Metabolism, (Hypo)Xanthine/Inosine containingHMDB00195
S-adenosylhomocysteine (SAH)0.917201777Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB00939
7-alpha-hydroxy-3-oxo-4-cholestenoate (7-Hoca)0.905038013LipidSterolHMDB12458
N6-carbamoylthreonyladenosine0.901351283NucleotidePurine Metabolism, Adenine containingHMDB41623
4-methyl-2-oxopentanoate0.900163956Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00695
phenol sulfate0.895634379Amino AcidPhenylalanine and Tyrosine MetabolismHMDB60015
catechol sulfate0.888697936XenobioticsBenzoate MetabolismHMDB59724
N-formylmethionine0.883181042Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB01015
N-acetylglycine0.849571206Amino AcidGlycine, Serine and Threonine MetabolismHMDB00532
3-methyl-2-oxovalerate0.846735413Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB03736
N-acetylvaline0.845346181Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB11757
N-acetylglutamine0.833885969Amino AcidGlutamate MetabolismHMDB06029
N2-methylguanosine0.830392642NucleotidePurine Metabolism, Guanine containingHMDB05862
pipecolate0.823379037Amino AcidLysine MetabolismHMDB00070
pyroglutamine*0.803705466Amino AcidGlutamate MetabolismNA
behenoyl sphingomyelin (d18:1/22:0)*0.790858718LipidSphingolipid MetabolismHMDB12103
S-1-pyrroline-5-carboxylate0.78963608Amino AcidGlutamate MetabolismHMDB01301
dihomo-linolenate (20:3n3 or n6)0.776451331LipidPolyunsaturated Fatty Acid (n3 and n6)HMDB02925
2,3-dihydroxyisovalerate0.77145439XenobioticsFood Component/PlantHMDB12141
3-indoxyl sulfate0.764540165Amino AcidTryptophan MetabolismHMDB00682
isovalerylcarnitine (C5)0.757242099Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00688
3-methylhistidine0.747523451Amino AcidHistidine MetabolismHMDB00479
acisoga0.742592537Amino AcidPolyamine MetabolismNA
stachydrine0.738906955XenobioticsFood Component/PlantHMDB04827
bilirubin (E,E)*0.725372028Cofactors and VitaminsHemoglobin and Porphyrin MetabolismNA
alpha-hydroxyisovalerate0.713458196Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00407
urea0.698589408Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB00294
picolinate0.668745666Amino AcidTryptophan MetabolismHMDB02243
N-acetylalanine0.662039938Amino AcidAlanine and Aspartate MetabolismHMDB00766
mannose0.660540199CarbohydrateFructose, Mannose and Galactose MetabolismHMDB00169
erythritol0.653529472XenobioticsFood Component/PlantHMDB02994
N1-Methyl-2-pyridone-5-carboxamide0.647825199Cofactors and VitaminsNicotinate and Nicotinamide MetabolismHMDB04193
1-(1-enyl-palmitoyl)-2-oleoyl-GPC (P-16:0/18:1)*0.644873759LipidPlasmalogenNA
salicylate0.633961091XenobioticsDrugHMDB01895
N2,N2-dimethylguanosine0.626824693NucleotidePurine Metabolism, Guanine containingHMDB04824
cytidine0.603171242NucleotidePyrimidine Metabolism, Cytidine containingHMDB00089
N-acetylputrescine0.593638396Amino AcidPolyamine MetabolismHMDB02064
arabitol/xylitol0.593162879CarbohydratePentose MetabolismNA
dopamine 3-O-sulfate0.575288491Amino AcidPhenylalanine and Tyrosine MetabolismHMDB06275
taurine0.56740618Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB00251
5-hydroxyhexanoate0.564056273LipidFatty Acid, MonohydroxyHMDB00525
trimethylamine N-oxide0.545734492LipidPhospholipid MetabolismHMDB00925
sphingomyelin (d18:1/24:1, d18:2/24:0)*0.542614676LipidSphingolipid MetabolismHMDB12107
octanoylcarnitine (C8)0.5137169LipidFatty Acid Metabolism(Acyl Carnitine)HMDB00791
1-palmitoylglycerol (16:0)0.511398384LipidMonoacylglycerolHMDB31074
pyruvate0.508474869CarbohydrateGlycolysis, Gluconeogenesis, and Pyruvate MetabolismHMDB00243
orotidine0.471388986NucleotidePyrimidine Metabolism, Orotate containingHMDB00788
choline0.471362468LipidPhospholipid MetabolismHMDB00097
3-hydroxyisobutyrate0.468297666Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00336
2-hydroxy-3-methylvalerate0.45385958Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00317
1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6)*0.436010948LipidPhospholipid MetabolismHMDB05334
2-hydroxybutyrate/2-hydroxyisobutyrate0.434021938Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismNA
isobutyrylcarnitine (C4)0.426317304Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00736
dimethylglycine0.423869124Amino AcidGlycine, Serine and Threonine MetabolismHMDB00092
orotate0.420368416NucleotidePyrimidine Metabolism, Orotate containingHMDB00226
glycerol 3-phosphate0.393518702LipidGlycerolipid MetabolismHMDB00126
glutarylcarnitine (C5-DC)0.392707933Amino AcidLysine MetabolismHMDB13130
2-oxoadipate0.392683371Amino AcidLysine MetabolismHMDB00225
phenyllactate (PLA)0.384143111Amino AcidPhenylalanine and Tyrosine MetabolismHMDB00779
creatine0.38383669Amino AcidCreatine MetabolismHMDB00064
aconitate [cis or trans]0.373308164EnergyTCA CycleNA
lysine0.354258615Amino AcidLysine MetabolismHMDB00182
uridine0.336698498NucleotidePyrimidine Metabolism, Uracil containingHMDB00296
hypoxanthine0.332357157NucleotidePurine Metabolism, (Hypo)Xanthine/Inosine containingHMDB00157
propionylcarnitine (C3)0.323563314LipidFatty Acid Metabolism (also BCAA Metabolism)HMDB00824
lidocaine0.314305068XenobioticsDrugHMDB14426
sphingomyelin (d18:1/20:0, d16:1/22:0)*0.311646884LipidSphingolipid MetabolismHMDB12102
allantoin0.310511824NucleotidePurine Metabolism, (Hypo)Xanthine/Inosine containingHMDB00462
acetoacetate0.304229944LipidKetone BodiesHMDB00060
N-acetylserine0.303900497Amino AcidGlycine, Serine and Threonine MetabolismHMDB02931
cholesterol0.297876847LipidSterolHMDB00067
1-palmityl-2-oleoyl-GPC (O-16:0/18:1)*0.281376295LipidPhospholipid MetabolismNA
N-acetylphenylalanine0.279795717Amino AcidPhenylalanine and Tyrosine MetabolismHMDB00512
citrate0.268756273EnergyTCA CycleHMDB00094
glycerophosphoinositol*0.260675045LipidPhospholipid MetabolismNA
sphingomyelin (d18:1/14:0, d16:1/16:0)*0.25401063LipidSphingolipid MetabolismHMDB12097
5-methyltetrahydrofolate (5MeTHF)0.235351276Cofactors and VitaminsFolate MetabolismHMDB01396
nicotinamide0.23412943Cofactors and VitaminsNicotinate and Nicotinamide MetabolismHMDB01406
N-acetylglutamate0.233537024Amino AcidGlutamate MetabolismHMDB01138
2′-deoxycytidine0.222556447NucleotidePyrimidine Metabolism, Cytidine containingHMDB00014
lactate0.218815116CarbohydrateGlycolysis, Gluconeogenesis, and Pyruvate MetabolismHMDB00190
N-delta-acetylornithine0.216153006Amino AcidUrea cycle; Arginine and Proline MetabolismNA
sphingomyelin (d18:1/18:1, d18:2/18:0)0.19802193LipidSphingolipid MetabolismHMDB12101
1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4)*0.194296878LipidPlasmalogenHMDB11220
adenosine0.192560425NucleotidePurine Metabolism, Adenine containingHMDB00050
palmitoyl sphingomyelin (d18:1/16:0)0.19245523LipidSphingolipid MetabolismNA
N-acetylmethionine0.190491809Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB11745
succinylcarnitine (C4-DC)0.183313485EnergyTCA CycleHMDB61717
deoxycarnitine0.182541062LipidCarnitine MetabolismHMDB01161
glycine0.174151121Amino AcidGlycine, Serine and Threonine MetabolismHMDB00123
1-palmityl-2-arachidonoyl-GPC (O-16:0/20:4)*0.172893524LipidPhospholipid MetabolismNA
tiglylcarnitine (C5:1-DC)0.172211183Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB02366
stearoyl sphingomyelin (d18:1/18:0)0.168532807LipidSphingolipid MetabolismHMDB01348
sulfate*0.166098961XenobioticsChemicalHMDB01448
guanosine0.146489833NucleotidePurine Metabolism, Guanine containingHMDB00133
3-methylglutarylcarnitine (2)0.141265288Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00552
4-acetamidobutanoate0.132120142Amino AcidPolyamine MetabolismHMDB03681
1-stearoyl-2-dihomo-linolenoyl-GPC (18:0/20:3n3 or 6)*0.111640103LipidPhospholipid MetabolismHMDB08047
glutamine0.108531754Amino AcidGlutamate MetabolismHMDB00641
1-palmitoyl-2-adrenoyl-GPC (16:0/22:4)*0.103696961LipidPhospholipid MetabolismHMDB07988
5alpha-pregnan-3beta,20alpha-diol disulfate0.1LipidSteroidNA
carnitine0.097404403LipidCarnitine MetabolismHMDB00062
dihomo-linoleate (20:2n6)0.080521924LipidPolyunsaturated Fatty Acid (n3 and n6)HMDB05060
mannitol/sorbitol0.071360102CarbohydrateFructose, Mannose and Galactose MetabolismHMDB00247
sphingomyelin (d18:2/16:0, d18:1/16:1)*0.071246136LipidSphingolipid MetabolismNA
N-acetylarginine0.070041075Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB04620
O-sulfo-L-tyrosine0.064946444XenobioticsChemicalNA
glutamate, gamma-methyl ester0.063557423Amino AcidGlutamate MetabolismHMDB61715
2-hydroxydecanoate0.057554247LipidFatty Acid, MonohydroxyNA
butyrylcarnitine (C4)0.055806957LipidFatty Acid Metabolism (also BCAA Metabolism)HMDB02013
3-hydroxybutyrate (BHBA)0.053314859LipidKetone BodiesHMDB00357
2-methylbutyrylcarnitine (C5)0.049217781Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00378
5-methyluridine (ribothymidine)0.040956702NucleotidePyrimidine Metabolism, Uracil containingHMDB00884
N-acetyl-beta-alanine0.037028106NucleotidePyrimidine Metabolism, Uracil containingNA
aspartate0.024689566Amino AcidAlanine and Aspartate MetabolismHMDB00191
3-hydroxyoctanoate0.019225594LipidFatty Acid, MonohydroxyHMDB01954
methylsuccinoylcarnitine0.0059297Amino AcidLeucine, Isoleucine and Valine MetabolismNA
isoleucine-0.003633005Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00172
C-glycosyltryptophan-0.00862718Amino AcidTryptophan MetabolismNA
7-methylguanine-0.009388262NucleotidePurine Metabolism, Guanine containingHMDB00897
pantothenate-0.012929614Cofactors and VitaminsPantothenate and CoA MetabolismHMDB00210
pseudouridine-0.014022822NucleotidePyrimidine Metabolism, Uracil containingHMDB00767
1-palmitoyl-2-arachidonoyl-GPC (16:0/20:4n6)-0.023052444LipidPhospholipid MetabolismHMDB07982
xanthosine-0.025413538NucleotidePurine Metabolism, (Hypo)Xanthine/Inosine containingHMDB00299
3-methylglutaconate-0.02545564Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00522
1-myristoyl-2-palmitoyl-GPC (14:0/16:0)-0.033804548LipidPhospholipid MetabolismHMDB07869
phenylalanine-0.040102593Amino AcidPhenylalanine and Tyrosine MetabolismHMDB00159
valine-0.044295241Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00883
citrulline-0.051663596Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB00904
glucuronate-0.057447356CarbohydrateAminosugar MetabolismHMDB00127
6-oxopiperidine-2-carboxylate-0.060018519Amino AcidLysine MetabolismHMDB61705
phosphoethanolamine-0.079314283LipidPhospholipid MetabolismHMDB00224
N-acetylglucosaminylasparagine-0.102985868CarbohydrateAminosugar MetabolismHMDB00489
leucine-0.104438234Amino AcidLeucine, Isoleucine and Valine MetabolismNA
1-stearoyl-2-arachidonoyl-GPC (18:0/20:4)-0.105544423LipidPhospholipid MetabolismHMDB08048
bilirubin (Z,Z)-0.114143557Cofactors and VitaminsHemoglobin and Porphyrin MetabolismHMDB00054
1-palmitoyl-2-oleoyl-GPC (16:0/18:1)-0.117039071LipidPhospholipid MetabolismHMDB07972
galactonate-0.119438892CarbohydrateFructose, Mannose and Galactose MetabolismHMDB00565
methionine-0.120474308Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB00696
1,2-dioleoyl-GPC (18:1/18:1)-0.144560674LipidPhospholipid MetabolismNA
1-stearoyl-2-oleoyl-GPC (18:0/18:1)-0.145607729LipidPhospholipid MetabolismHMDB08038
1-stearoyl-2-docosahexaenoyl-GPC (18:0/22:6)-0.151218084LipidPhospholipid MetabolismNA
erythronate*-0.163423988CarbohydrateAminosugar MetabolismHMDB00613
N-acetylthreonine-0.163596033Amino AcidGlycine, Serine and Threonine MetabolismHMDB62557
arabonate/xylonate-0.167668407CarbohydratePentose MetabolismNA
methylmalonate (MMA)-0.173863318LipidFatty Acid Metabolism (also BCAA Metabolism)HMDB00202
1-palmitoyl-2-dihomo-linolenoyl-GPC (16:0/20:3n3 or 6)*-0.182467741LipidPhospholipid MetabolismNA
N-acetylneuraminate-0.186100182CarbohydrateAminosugar MetabolismHMDB00230
dimethylarginine (SDMA + ADMA)-0.196773066Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB01539
1,2-dipalmitoyl-GPC (16:0/16:0)-0.205784678LipidPhospholipid MetabolismHMDB00564
acetylcarnitine (C2)-0.212759832LipidFatty Acid Metabolism(Acyl Carnitine)HMDB00201
N-acetylhistidine-0.212977839Amino AcidHistidine MetabolismHMDB32055
ornithine-0.221208011Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB03374
1-palmitoyl-2-palmitoleoyl-GPC (16:0/16:1)*-0.222258373LipidPhospholipid MetabolismNA
indoleacetate-0.244129138Amino AcidTryptophan MetabolismHMDB00197
3-ureidopropionate-0.26305148NucleotidePyrimidine Metabolism, Uracil containingHMDB00026
1-(1-enyl-stearoyl)-2-docosahexaenoyl-GPE (P-18:0/22:6)*-0.287521485LipidPlasmalogenHMDB11394
methionine sulfone-0.288546539Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismNA
5-methylthioadenosine (MTA)-0.28874055Amino AcidPolyamine MetabolismHMDB01173
tryptophan-0.292915649Amino AcidTryptophan MetabolismHMDB00929
1-stearoyl-2-linoleoyl-GPC (18:0/18:2)*-0.312073093LipidPhospholipid MetabolismNA
asparagine-0.318640783Amino AcidAlanine and Aspartate MetabolismHMDB00168
1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4)*-0.334612758LipidPlasmalogenHMDB11352
1-oleoyl-2-linoleoyl-GPC (18:1/18:2)*-0.365364827LipidPhospholipid MetabolismNA
1-palmitoyl-2-linoleoyl-GPC (16:0/18:2)-0.376666069LipidPhospholipid MetabolismHMDB07973
1-methylnicotinamide-0.3818196Cofactors and VitaminsNicotinate and Nicotinamide MetabolismHMDB00699
succinamic acid-0.390140865XenobioticsChemicalNA
gluconate-0.390647894XenobioticsFood Component/PlantHMDB00625
N1-methyladenosine-0.402878078NucleotidePurine Metabolism, Adenine containingHMDB03331
choline phosphate-0.404538137LipidPhospholipid MetabolismHMDB01565
1,3-propanediol-0.406513834XenobioticsChemicalNA
cysteine-0.416342573Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB00574
sucrose-0.419796468CarbohydrateDisaccharides and OligosaccharidesHMDB00258
1-methyl-4-imidazoleacetate-0.428811931Amino AcidHistidine MetabolismHMDB02820
ribonate-0.430438843CarbohydratePentose MetabolismHMDB00867
1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4)*-0.431921855LipidPlasmalogenHMDB05779
glucose-0.43579414CarbohydrateGlycolysis, Gluconeogenesis, and Pyruvate MetabolismHMDB00122
2-aminobutyrate-0.447827309Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB00650
1-(1-enyl-palmitoyl)-2-docosahexaenoyl-GPE (P-16:0/22:6)*-0.455833423LipidPlasmalogenHMDB05780
1,5-anhydroglucitol (1,5-AG)-0.456275121CarbohydrateGlycolysis, Gluconeogenesis, and Pyruvate MetabolismHMDB02712
anthranilate-0.456711996Amino AcidTryptophan MetabolismHMDB01123
galactitol (dulcitol)-0.478928546CarbohydrateFructose, Mannose and Galactose MetabolismHMDB00107
kynurenate-0.500371108Amino AcidTryptophan MetabolismHMDB00715
2′-deoxyuridine-0.505414414NucleotidePyrimidine Metabolism, Uracil containingHMDB00012
kynurenine-0.506769908Amino AcidTryptophan MetabolismHMDB00684
cis-4-decenoylcarnitine (C10:1)-0.535390336LipidFatty Acid Metabolism(Acyl Carnitine)NA
ethylmalonate-0.574611193Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00622
xanthine-0.591803553NucleotidePurine Metabolism, (Hypo)Xanthine/Inosine containingHMDB00292
argininosuccinate-0.599113576Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB00052
pyridoxal-0.60738315Cofactors and VitaminsVitamin B6 MetabolismHMDB01545
5-oxoproline-0.624921389Amino AcidGlutathione MetabolismHMDB00267
betaine-0.658899986Amino AcidGlycine, Serine and Threonine MetabolismHMDB00043
N6,N6,N6-trimethyllysine-0.671169323Amino AcidLysine MetabolismHMDB01325
alpha-ketoglutarate-0.671519195EnergyTCA CycleHMDB00208
hippurate-0.675000644XenobioticsBenzoate MetabolismHMDB00714
beta-hydroxyisovaleroylcarnitine-0.687835361Amino AcidLeucine, Isoleucine and Valine MetabolismNA
3-hydroxy-3-methylglutarate-0.739282917LipidMevalonate MetabolismHMDB00355
3-(4-hydroxyphenyl)lactate-0.764110907Amino AcidPhenylalanine and Tyrosine MetabolismHMDB00755
alanine-0.776456587Amino AcidAlanine and Aspartate MetabolismHMDB00161
myo-inositol-0.794154378LipidInositol MetabolismHMDB00211
2-piperidinone-0.81095547XenobioticsFood Component/PlantHMDB11749
5,6-dihydrothymine-0.81699694NucleotidePyrimidine Metabolism, Thymine containingHMDB00079
1-oleoyl-GPC (18:1)-0.824233532LipidLysolipidHMDB02815
malonate-0.85467407LipidFatty Acid SynthesisHMDB00691
glutamate-0.860731898Amino AcidGlutamate MetabolismHMDB00148
2-methylcitrate-0.870958093EnergyTCA CycleHMDB00379
succinate-0.907442819EnergyTCA CycleHMDB00254
maleate-0.924369834LipidFatty Acid, DicarboxylateHMDB00176
threonate-0.926433244Cofactors and VitaminsAscorbate and Aldarate MetabolismHMDB00943
pyridoxate-0.95231917Cofactors and VitaminsVitamin B6 MetabolismHMDB00017
tartarate-0.954884XenobioticsFood Component/PlantHMDB00956
threonine-0.959417716Amino AcidGlycine, Serine and Threonine MetabolismHMDB00167
tartronate (hydroxymalonate)-0.973116753XenobioticsBacterial/FungalHMDB35227
3-methoxytyrosine-1.005109166Amino AcidPhenylalanine and Tyrosine MetabolismHMDB01434
citramalate-1.015885306Amino AcidGlutamate MetabolismHMDB00426
proline-1.028132588Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB00162
glycerol-1.059922988LipidGlycerolipid MetabolismHMDB00131
trans-4-hydroxyproline-1.061312638Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB00725
gulonate*-1.065746545Cofactors and VitaminsAscorbate and Aldarate MetabolismHMDB03290
dimethylmalonic acid-1.079518427LipidFatty Acid, DicarboxylateHMDB02001
tyrosine-1.169479885Amino AcidPhenylalanine and Tyrosine MetabolismHMDB00158
1-stearoyl-GPC (18:0)-1.177211068LipidLysolipidHMDB10384
glycerate-1.202282795CarbohydrateGlycolysis, Gluconeogenesis, and Pyruvate MetabolismHMDB00139
methionine sulfoxide-1.247251482Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismHMDB02005
isovalerate (i5:0)-1.251178292Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB00718
adenine-1.265140187NucleotidePurine Metabolism, Adenine containingHMDB00034
malate-1.268342019EnergyTCA CycleHMDB00156
arginine-1.270500092Amino AcidUrea cycle; Arginine and Proline MetabolismHMDB00517
serine-1.316200721Amino AcidGlycine, Serine and Threonine MetabolismHMDB00187
uracil-1.326198804NucleotidePyrimidine Metabolism, Uracil containingHMDB00300
N-acetyl-aspartyl-glutamate (NAAG)-1.333747042Amino AcidGlutamate MetabolismHMDB01067
1-palmitoyl-GPC (16:0)-1.358464356LipidLysolipidHMDB10382
carboxyethyl-GABA-1.359609408Amino AcidGlutamate MetabolismHMDB02201
homovanillate (HVA)-1.366187052Amino AcidPhenylalanine and Tyrosine MetabolismHMDB00118
histidine-1.404231999Amino AcidHistidine MetabolismHMDB00177
homocarnosine-1.562172137PeptideDipeptide DerivativeHMDB00745
N-acetyltaurine-1.625263475Amino AcidMethionine, Cysteine, SAM and Taurine MetabolismNA
4-guanidinobutanoate-1.650932518Amino AcidGuanidino and Acetamido MetabolismHMDB03464
N-acetylaspartate (NAA)-1.822523265Amino AcidAlanine and Aspartate MetabolismHMDB00812
methylsuccinate-1.854821214Amino AcidLeucine, Isoleucine and Valine MetabolismHMDB01844
oxalate (ethanedioate)-2.058090147Cofactors and VitaminsAscorbate and Aldarate MetabolismHMDB02329
*While no identifying patient information is included in this table, patient permission was obtained prior to data publication.
Methods

Miller MJ, Kennedy AD, Eckhart AD, Burrage LC, Wulff JE, Miller LA, Milburn MV, Ryals JA, Beaudet AL, Sun Q, Sutton VR, Elsea SH “Untargeted metabolomic analysis for the clinical screening of inborn errors of metabolism.” J Inherit Metab Dis. 2015 April 15; 38 : 1029-39. Pubmed PMID: 25875217

Polyol pathway activation in the CSF uniquely correlates with pain and opioid use
Kyla Shade BS, Jon Berner MD PhD, Sarah Elsea PhD

Although molecular signatures of chronic pain have previously been identified in the CSF looking at small subset of markers (NGF, substance P, 5-HIAA) , examination of the high dimensional metabolome (N=300) in clinical populations has only recently become technically feasible. We report pilot data from a small clinical sample (N=27) of refractory patients.

Exploratory data analysis reviewed the correlation matrix defined by demographic variables (age, gender), structured symptoms checklists (disability, anxiety, depression, autism), concurrent medication use (antidepressants, stimulants, benzodiazepines, lithium, opioids, ketamine), chief complaint (pain, bipolar disorder) and a subset of 18 metabolic variables z-scores. These variables were selected out of the larger metabolome given frequency of appearance greater or lower than 2 z-scores in an individual patient metabolome profile.

Activation of the polyol pathway was uniquely seen in pain patients on opioids. Sorbitol z-scores correlated highly with both pain (r. = 0.451, p.=0. 018) and opioid use (r. =0.573, p.=0.002). Upstream (glucose) and downstream metabolites (fructose) had consistent r. values for both pain (glucose r. = 0.33, fructose r. = 0.11) and opioid use (glucose r.= 0.36, fructose r. = 0.38) although p. values were less compelling (3/4 < p. = 0.1).

Although direction of causation cannot be established with correlational analysis, there is a wealth of evidence implicating polyol pathway activation in painful diabetic neuropathy, subtypes of Charcot-Marie-Tooth Disease, leukoencephalopathy in bipolar disorder, and disability status in multiple sclerosis. Further research is indicated to replicate exploratory univariate analysis, create more sensitive and robust multivariate tools, define possible predictive validity for opioid and/or aldose reductase inhibitor response in drug-naive patients, and potentially link this clinical data with basic science findings on TRP regulation of the sickness behavioral response driven by osmolality changes during hibernation and/or starvation.