ArticleJournal of anesthesia and translational medicine2024
Roles of orexinergic and noradrenergic neuronal activity in ketamine-induced analgesia: A study using an orexin/ataxin-3 transgenic rat model.
Article in Journal of anesthesia and translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Orexin, a neuropeptide, physiologically interacts with locus coeruleus noradrenergic (LC-NA) activity. We hypothesized that this interaction affects ketamine-induced acute analgesia. Methods: We assessed ketamine-induced acute analgesia in transgenic (TG) and wild-type (WT) rats with genetically degraded orexinergic neurons using hotplate and tail-flick tests. We examined the effect of the LC-NA toxin, Results: TG exhibited a decreased percentage of maximum possible effect area under the curve (AUC) for hotplate latency (WT: 1315.0 ± 1026.0; TG: 439.6 ± 831.5; P = 0.016) but not tail-flick latency (WT: 1203.0 ± 332.4; TG: 1127.0 ± 512.4; P = 0.732). Orexin (10 nmol, ICV) increased hotplate latency AUC in DSP4-free WT (control: 220.2 ± 227.2; orexin 10: 1575.0 ± 760.2; P = 0.004), DSP4-free TG (control: 119.9 ± 197.1; orexin 10: 866.5 ± 213.2; P = 0.001), DSP4-treated WT (control: -20.0 ± 350.5; orexin 10: 775.4 ± 485.2; P = 0.048), and DSP4-treated TG (control: -181.3 ± 272.6; orexin: 1038.0 ± 652.6; P = 0.040) rats. AUC with orexin 10 was lower in DSP4-treated WT rats than in DSP4-free WT rats (1575.0 ± 760.2 vs. 775.4 ± 485.2; P = 0.025). Co-administration of SB-334867 (20 nmol, ICV) with orexin blocked the effect of orexin on hotplate latency in DSP4-free but not DSP4-treated rats. TG rats had lower noradrenaline contents (pg/mg tissue) in the pons (WT: 341.9 ± 36.3; TG: 279.6 ± 54.4; P=0.038) and cerebral cortex (WT: 1195.1 ± 36.1; TG: 120.1 ± 32.6; P=0.042), but not in the hypothalamus (WT: 895.6 ± 130.4; TG 822.3 ± 1140.3; P=0.373). Orexin levels decreased in all brain regions of TG rats (pons: WT: 7.6 ± 3.2; TG: 1.1 ± 0.3, P = 0.001; hypothalamus: WT: 12.6 ± 2.9; TG: 2.8 ± 1.4, P<0.0001; cerebral cortex: WT: 2.1 ± 0.6; TG: 0.7 ± 0.3, P = 0.001). Conclusions: The role of orexin in ketamine-induced acute analgesia partly depends on LC-NA activity.
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