naloxone and Dilatation--Pathologic

The present studies examined the involvement of the rostral ventral medulla (RVM) in modulating the visceromotor response (VMR) evoked by urinary bladder distension (UBD) in adult female rats. The VMR was indexed by electromyographic (EMG) responses of the abdominal external oblique muscle to UBD. Experiment 1 showed that the predominant effect of electrical stimulation of the RVM in normal rats was to produce intensity-dependent inhibition of the VMR (54% of sites sampled). Facilitatory, biphasic, or no effects were obtained at the remaining sites. Experiment 2 showed that RVM-induced inhibition of the VMR was significantly attenuated by intraperitoneal (i.p.) administration of naloxone but not saline vehicle. In experiment 3, we examined the effect of lesions of the RVM in rats with inflamed bladders because previous research has shown that an endogenous opioid inhibitory system is engaged by bladder inflammation. Electrolytic lesions of the RVM but not sham lesions of the RVM significantly increased the VMR to graded UBD in rats with augmented VMRs induced by prior inflammation of the bladder. The present data suggest that the RVM can inhibit the VMR to UBD, acting in part via an opioid-inhibitory system, and that bladder inflammation can recruit the RVM to produce a net inhibitory effect on the VMR to UBD.. Stimulation of the RVM resulted in inhibitory, facilitatory, and biphasic modulation of the visceromotor reflex to urinary bladder distension. Inhibitory effects of stimulation were attenuated by naloxone, and lesions of the RVM enhanced the VMR in rats with inflamed bladders. These data indicate an important role of the RVM in modulating bladder pain.

Topics: Analysis of Variance; Animals; Dilatation, Pathologic; Efferent Pathways; Electric Stimulation; Electrodes; Electromyography; Female; Inflammation; Injections, Intraperitoneal; Medulla Oblongata; Naloxone; Narcotic Antagonists; Pain Measurement; Rats; Rats, Sprague-Dawley; Reflex; Urinary Bladder; Viscera; Visceral Afferents

It has been shown that the behavioural responses to chemically evoked visceral nociception are increased in transgenic mice lacking the kappa-opioid receptor (KOR). The aim of the present study was to evaluate the contribution of KOR in mechanically evoked visceral pain by performing colorectal distension (CRD) and monitoring the subsequent visceromotor response (VMR) in control mice (KOR(+/+)) and in mice lacking KOR (KOR(-/-)). Pseudo-affective visceral pain responses were evoked in conscious mice using increasing (10-80 mmHg) and repeated (12 x 55 mmHg) phasic CRD paradigms. The resulting VMR was determined by monitoring the electromyographic activity of the abdominal muscle. The increasing and repeated CRD paradigms, respectively, evoked similar responses in both KOR(+/+) and KOR(-/-) mice. The selective KOR-agonists U-69593 (5 and 25 mg kg(-1), s.c.) and asimadoline (25 mg kg(-1), s.c.) significantly decreased the VMR in KOR(+/+) mice, while having no effect in KOR(-/-) mice. In contrast, the selective mu-opioid receptor agonist fentanyl significantly reduced the VMR in both types of mice and appeared more efficacious in KOR(-/-) mice. The opioid receptor antagonist naloxone (0.3-30 mg kg(-1) s.c.) did not affect the response to CRD in C57BL/6 mice at any dose tested. In conclusion, the data confirm that the KOR agonists used in this study inhibit the VMR to CRD in mice by acting via KOR receptors. In addition, the data suggest that the endogenous opioid system is not likely to modulate the VMR to mechanically evoked visceral pain in mice.

Topics: Analgesics, Opioid; Animals; Colon; Dilatation, Pathologic; Electromyography; Female; Fentanyl; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Naloxone; Narcotic Antagonists; Nociceptors; Pain; Pain Measurement; Receptors, Opioid, kappa; Receptors, Opioid, mu; Rectum

Abdominal electromyographic (EMG) responses to noxious intensities of urinary bladder distention (UBD) are significantly enhanced 24 hours after zymosan-induced bladder inflammation in adult female rats. This inflammation-induced hypersensitivity is concomitantly inhibited by endogenous opioids because intraperitoneal (i.p.) naloxone administration before testing significantly increases EMG response magnitude to UBD. This inhibitory mechanism is not tonically active because naloxone does not alter EMG response magnitude to UBD in rats without inflammation. At the dose tested, naloxone does not affect bladder compliance in rats with or without inflammation. The effects of i.p. naloxone probably result from blockade of a spinal mechanism because intrathecal naloxone also significantly enhances EMG responses to UBD in rats with inflammation. Rats exposed to bladder inflammation from P90-P92 before reinflammation at P120 show similar hypersensitivity and concomitant opioid inhibition, with response magnitudes being no different from that produced by inflammation at P120 alone. In contrast, rats exposed to bladder inflammation from P14-P16 before reinflammation at P120 show markedly enhanced hypersensitivity and no evidence of concomitant opioid inhibition. These data indicate that bladder inflammation in adult rats induces bladder hypersensitivity that is inhibited by an endogenous opioidergic mechanism. This mechanism can be disrupted by neonatal bladder inflammation.. The present study observed that bladder hypersensitivity resulting from acute bladder inflammation is suppressed by an opioid-inhibitory mechanism. Experiencing bladder inflammation during the neonatal period can impair the expression of this opioid inhibitory mechanism in adulthood. This suggests that bladder insults during development may permanently alter visceral sensory systems and may represent 1 cause of painful bladder disorders.

Topics: Age Factors; Analgesics, Opioid; Analysis of Variance; Animals; Animals, Newborn; Dilatation, Pathologic; Disease Models, Animal; Electromyography; Female; Inflammation; Muscle Contraction; Naloxone; Narcotic Antagonists; Pain Measurement; Rats; Rats, Sprague-Dawley; Reflex; Urinary Bladder Diseases; Viscera; Zymosan

To establish a visceral pain model via colorectal distension (CRD) and to evaluate the efficiency of behavioral responses of CRD by measuring the score of abdominal withdrawal reflex (AWR) in rats.. Thirty-eight male SD rats weighing 180-240 g were used to establish the visceral pain model. The rat was inserted intra-anally with a 7 cm long flexible latex balloon under ether anesthesia, and colorectal distensions by inflating the balloon with air were made 30 min after recovering from the anesthesia. Five AWR scores (AWR0 to AWR4) were used to assess the intensity of noxious visceral stimuli. It was regarded as the threshold of the minimal pressure (kPa). For abdominal flatting was induced by colorectal distension.. A vigorous AWR to distension of the descending colon and rectum was found in 100% of the awake rats tested. The higher the pressure of distension, the higher the score of AWR. The distension pressures of 0, 2.00, 3.33, 5.33 and 8.00 kPa produced different AWR scores (P<0.05). The pain threshold of AWR was constant for up to 80 min after the initial windup (first 1-3 distensions), the mean threshold was 3.69+/-0.35 kPa. Systemic administration of morphine sulfate elevated the threshold of visceral pain in a dose-dependent and naloxone reversible manner.. Scoring the AWR during colorectal distensions can assess the intensity of noxious visceral stimulus. Flatting of abdomen (AWR 3) to CRD as the visceral pain threshold is clear, constant and reliable. This pain model and its behavioral assessment are good for research on visceral pain and analgesics.

Topics: Abdominal Pain; Analgesics; Animals; Behavior, Animal; Catheterization; Colon; Dilatation, Pathologic; Disease Models, Animal; Male; Morphine; Naloxone; Narcotic Antagonists; Pain Threshold; Rats; Rats, Sprague-Dawley; Rectum; Reflex; Reproducibility of Results; Time Factors; Viscera

Colon vascular ectasias are a common cause of lower intestinal bleeding among the elderly. The lesions may be difficult to diagnose at colonoscopy because they are small and their appearance may be influenced by the patient's blood pressure, blood volume, and narcotic sedation during the procedure. The purpose of this study was to determine whether naloxone influenced the appearance of colon vascular ectasias at colonoscopy.. One hundred forty-four patients older than 60 years undergoing complete colonoscopy participated in the study. Medications were given in the usual doses. After a 2-minute inspection of the cecum and ascending colon, naloxone was given, followed by another 2-minute observation period. Photographic documentation of areas of interest was obtained before and after administration of naloxone.. One hundred fourteen patients (79%) had no ectasias before or after administration of naloxone. Fourteen (9.7%) initially had normal vessels, and the vessels became more prominent; 4 (2.7%) initially had no ectasias, but ectasias later developed. Four patients (2.7%) had ectasias before administration of naloxone that did not change; 8 (5.4%) had ectasias before administration of naloxone that increased in size (3 patients), number (7 patients), or both (2 patients).. Naloxone can enhance the appearance of normal colonic vasculature and ectasias. Naloxone is an important adjunctive medication for patients undergoing examinations for lower intestinal bleeding.

Topics: Blood Vessels; Colon; Colonic Diseases; Colonoscopy; Dilatation, Pathologic; Gastrointestinal Hemorrhage; Humans; Image Enhancement; Injections, Intravenous; Middle Aged; Naloxone; Narcotic Antagonists

Topics: Aged; Blood Vessels; Colon; Colonic Diseases; Dilatation, Pathologic; Female; Gastrointestinal Hemorrhage; Hot Temperature; Humans; Intestinal Mucosa; Naloxone; Narcotic Antagonists; Therapeutic Irrigation