Delayed stress-induced colonic hypersensitivity in male Wistar rats: role of neurokinin-1 and corticotropin-releasing factor-1 receptors

Abstract

The mechanism(s) underlying stress-induced colonic hypersensitivity (SICH) are incompletely understood. Our aims were to assess the acute and delayed (24 h) effect of water avoidance (WA) stress on visceral nociception in awake male Wistar rats and to evaluate the role of two stress-related modulation systems: the substance P/neurokinin-1 receptor (SP/NK(1)R) and the corticotropin-releasing factor (CRF)/CRF(1) receptor (CRF/CRF(1)R) systems, as well as the possible involvement of the sympathetic nervous system. Visceral pain responses were measured as the visceromotor response to colorectal distension (CRD) at baseline, immediately after WA and again 24 h later. The NK(1)R antagonists RP-67580 and SR-140333 and the CRF(1)R antagonist CP-154526 were injected 15 min before WA or 1 h before the CRD on day 2. Chemical sympathectomy was performed by repeated injection of 6-hydroxydopamine. WA stress resulted in a significant increase in the visceromotor response on day 2, but no change immediately after WA. Injection of CP-154526 abolished delayed SICH when applied either before WA stress or before the CRD on day 2. Both NK(1)R antagonists only decreased SICH when injected before the CRD on day 2. Chemical sympathectomy did not affect delayed SICH. Our results indicate that in male Wistar rats, both NK(1)R and CRF(1)R activation, but not sympathetic nervous system activation, play a role in the development of SICH.

Chronic psychological stress enhances nociceptive processing in the urinary bladder in high-anxiety rats

“…A number of studies suggest that the CRF system might also be modulating visceral sensitivity related to stress [12,13,14,37]. With regard to the bladder, CRF is abundantly expressed in areas involved in the control of micturition (i.e., Barrington's nucleus, lumbosacral areas of the spinal cord) and administration of various CRF receptor agonists and antagonists alters cystometric parameters [38,39,40].…”

“…A number of laboratory studies have demonstrated SIH to colorectal stimulation [10,11,12,13,14], and rats that are genetically predisposed to enhanced levels of anxiety exhibit exaggerated responses to colorectal distension [15]. In contrast, few laboratory reports exist about the relationship between stress and hypersensitivity of the urinary bladder.…”

Involvement of vasopressin 3 receptors in chronic psychological stress-induced visceral hyperalgesia in rats

“…Rats were deeply anesthetized with pentobarbital sodium (45 mg/kg ip, Nembutal; Abbott Laboratories, North Chicago, IL) and equipped with electrodes (Teflon-coated stainless steel wire; AstraZeneca, Mölndal, Sweden) implanted into the external oblique musculature, just superior to the inguinal ligament, as previously described (8,46). Electrode leads were then tunneled subcutaneously and externalized laterally (left abdominal side) for future access through a plastic fistula (AstraZeneca).…”

“…The EMG activity was rectified, and the increase in the area under the curve of EMG amplitude (during each CRD pulse) over baseline (before CRD) was recorded as the response to distension. The same procedures have been previously used to assess pain-related responses to CRD in rats (8,46).…”

“…We selected this model because it exhibits sustained visceral hyperalgesia and anxiety-like behaviors and has previously been shown to be sensitive to CRF 1 receptor antagonists (8,46). Specifically, we wanted to address the following questions: 1) Does daily application of the V 3 receptor antagonist prevent the development of visceral hyperalgesia during repeated stress?…”