Disruption of thermal nociceptive behaviour in mice mutant for the schizophrenia-associated genes NRG1, COMT and DISC1.
Abnormalities in pain perception, especially altered warmth and heat pain sensitivity, have been reported in schizophrenia. Therefore, genes associated with schizophrenia, including neuregulin-1 (NRG1), catechol-O-methyltranferase (COMT) and disrupted-in-schizophrenia-1 (DISC1), may play a role in modulating the physiological and psychological effects of pain stimuli in such patients. Thermal pain sensitivity was assessed in NRG1, COMT and DISC1 mutant mice, and the anti-nociceptive effects of acute Delta(9)-tetrahydrocannabinol (THC) were compared in NRG1 and COMT mutants. At baseline, deletion of NRG1 and DISC1 each reduced thermal pain sensitivity, while deletion of COMT increased pain sensitivity. Neither NRG1 nor COMT deletion altered the anti-nociceptive effects of acute systemic THC (8.0mg/kg). These results indicate a differential contribution of NRG1 and DISC1 vis-à-vis COMT to the processing of thermal nociceptive stimuli and extend their phenotypic relationship to psychotic illness.
Walsh
J
J
School of Physiotherapy, Royal College of Surgeons in Ireland, Dublin, Ireland. cotuathaigh@rcsi.ie
Tighe
O
O
Lai
D
D
Harvey
R
R
Karayiorgou
M
M
Gogos
J A
JA
Waddington
J L
JL
O'Tuathaigh
C M P
CM
D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D002394:Catechol O-Methyltransferase / Q000172:deficiency / Q000235:genetics*; D013759:Dronabinol / Q000627:therapeutic use; D005260:Female; D006930:Hyperalgesia / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016296:Mutagenesis / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics*; D020890:Neuregulin-1 / Q000172:deficiency / Q000235:genetics*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012737:Sex Factors
D018712:Analgesics, Non-Narcotic; C498794:Disc1 protein, mouse; D009419:Nerve Tissue Proteins; D020890:Neuregulin-1; C490581:Nrg1 protein, mouse; D013759:Dronabinol; D002394:Catechol O-Methyltransferase