title: GABAergic modulation of diffuse noxious inhibitory controls (DNIC): a test by use of lorazepam.
abstract: Diffuse noxious inhibitory controls (DNIC) are an important supra-spinal mechanism of pain inhibition. Neurotransmitters and modulators involved in DNIC are serotonin and endogenous opioids. The influence of substances binding to the GABA(A) receptor complex, which has been suggested to play an important role in descending pain inhibition on DNIC has not yet been investigated. The aim of the present study was to find out whether the inhibitory action of DNIC might also be mediated by GABAergic mechanisms. Therefore, DNIC modulation via GABAergic mechanisms was studied in a double blind, placebo-controlled crossover design by oral application of 0.02 mg/kg(body weight )lorazepam in 20 healthy subjects. DNIC inhibition was induced by heterotopically administered tonic heat. The inhibitory effect was assessed by use of a multiple staircase method, measuring electrocutaneous detection, and pain thresholds in parallel. Concurrent tonic heat stimuli, at both painful and non-painful levels, significantly increased the electrical pain threshold whereas the electrical detection threshold was not affected. This pain-specific inhibitory effect did not differ significantly between sessions with lorazepam and placebo. Accordingly, lorazepam did not modify the inhibitory action of DNIC although lorazepam generally increased heat pain threshold. The results of the present study provided no evidence for DNIC being mediated by activation of the GABA(A) receptor complex.
authors.affiliation: Physiological Psychology, Otto-Friedrich University Bamberg, Markusplatz 3, Bamberg 96045, Germany. miriam.kunz@ppp.uni-bamberg.de
authors.forename: Miriam
authors.initials: M
authors.lastname: Kunz
authors.forename: Kirsten Elisabeth
authors.initials: KE
authors.lastname: Scholl
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schu
authors.forename: Stefan
authors.initials: S
authors.lastname: Lautenbacher
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D018757:GABA Modulators / Q000627:therapeutic use*; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008140:Lorazepam / Q000627:therapeutic use*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D018757:GABA Modulators; D008140:Lorazepam