Basic–alimentary tractThe Role of Neurokinin 1 Receptors in the Maintenance of Visceral Hyperalgesia Induced by Repeated Stress in Rats
Section snippets
Animals
Adult male Wistar rats (250–275 g) were purchased from Harlan (Indianapolis, IN). Animals were maintained on a normal light-dark cycle, housed in pairs or singly when equipped with a chronic intrathecal catheter. They were provided with food and water ad libitum. All protocols were approved by the Institutional Animal Care and Use Committee at the VA Greater Los Angeles Healthcare System (Los Angeles, CA).
Implantation of electromyographic electrodes
Adult male rats were deeply anesthetized with pentobarbital sodium (45 mg/kg, Nembutal;
IP injection of the NK1R antagonist SR140333
There was a significant increase of the VMR following repeated exposure to WA stress at day 11 (CRD#2) compared with baseline (CRD#1). The increase was significant for the pressures of 40 and 60 mm Hg (P < .05, repeated-measures ANOVA followed by Bonferroni posttest). One hour later, the effect of systemic application of the NK1R antagonist SR140333 (at the previously established dose of 1 mg/kg27) or vehicle was tested on the VMR to CRD#3. As shown in Figure 1A, SR140333 abolished the
Discussion
The present study expands on previous observations that repeated psychological stress in male Wistar rats results in a phenotype characterized by increased autonomic responsiveness, anxiety-like behavior, and sustained visceral hyperalgesia, consistent with stress sensitization.35 Our results point to a major role for the SP/NK1R signaling system in mediating the visceral hyperalgesia component of this model, because the stress-induced exaggerated VMR to CRD was abolished by intrathecal
Summary and Conclusions
The findings from the present study show an up-regulation of NK1R on spinal neurons in a model of chronic WA stress associated with sustained visceral hyperalgesia. The pharmacologic efficacy of a spinal treatment with an NK1R antagonist to abolish the enhanced visceral response in this model suggests an important contribution of the spinal NK1R-expressing neurons in visceral hyperalgesia. The lack of enhanced SP gene expression in DRG or enhanced SP spinal release suggests that increased
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Cited by (0)
Supported by National Institutes of Health grants P50 DK64539 (to E.A.M.), R24 AT00281 (to E.A.M.), DK47343 (to C.P.), DK41301 Morphology and Imaging Core (to C.S.) and Antibody Core (to G.O.), R01 DK57037 (to C.S.), and DK54155 (to C.S.); a Fellowship Award from the Crohn’s and Colitis Foundation (to S.S.); GlaxoSmithKline (Neurology and GI Centre of Excellence for Drug Discovery, Harlow, England); and R21 DK071767-01 (to S.B.).