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Biomedical subjects

Andreas Sandner-Kiesling

Publications and source records attributed to Andreas Sandner-Kiesling.

5 recordsLinked to original sources

Effect of kappa opioid agonists on visceral nociception induced by uterine cervical distension in rats.

Although uterine distension in rats results in an escape reflex, there exists no model of uterine cervical distension (UCD), the pain stimulus during the first stage of labor. The aims of this study were to develop such a model in virgin rats and to test whether peripherally restricted kappa opioid receptor (KOR) agonists (ADL 10-0101, ADL 10-0102, ADL 10-0116) inhibit responses to UCD. Under intravenous (i.v.) pentobarbital and alpha-chloralose anesthesia, fine metal rods were inserted in both uterine cervical osses through a small midline laparotomy. UCD was performed by manual separation of the rods (25-100 g). Single-unit afferent responses in hypogastric nerve or reflex rectus abdominis electromyographic (EMG) activity were determined before and after i.v. KOR agonists. UCD resulted in a stimulus-dependent increase in single-unit afferent activity. Units could be characterized as low threshold (mean threshold 6.6+/-2.7 g), or high threshold (mean threshold 55+/-8.8 g); all were C fibers, all responded to topical bradykinin. ADL 10-0116 (10 mg/kg) reduced the afferent response to UCD. Reflex EMG response occurred over a distension force range of 25-100 g, unaffected by i.v. saline. All three KOR agonists produced a dose-dependent, naloxone-reversible inhibition of the EMG response with a potency relationship of ADL 10-0102 (ED50 0.04 mg/kg)>ADL 10-0101 (ED50 0.65 mg/kg)=ADL 10-0116 (ED50 0.60 mg/kg). These data support the use of acute UCD as a noxious stimulus, inducing afferent and reflex activity. Like other visceral stimuli, UCD is sensitive to inhibition by KOR agonists.

Analgesics, Opioid↗

Side-effects after inhalational anaesthesia for paediatric cerebral magnetic resonance imaging.

BACKGROUND: The aim of this study was to evaluate the type, incidence and duration of postprocedure side-effects in 168 children within the first 72 h after inhalational anaesthesia for magnetic resonance imaging (MRI). METHODS: Premedication and induction followed standardized routines. Maintenance of anaesthesia was performed with inhalational anaesthetics solely: isoflurane (n=60 of 112; 53%), sevoflurane (n=32 of 112; 29%), desflurane (n=12 of 112; 11%) or halothane (n= 8 of 112; 7%) using a strapped on face mask (FiO2=0.4; flow 5 l.min-1). When indicated, gadolinium was administered (n=45; OF 112; 40%). RESULTS: One hundred and twelve of 168 parents (67%) responded to questionnaires. In these 112 children, pathological MR findings were found supratentorially (n=31; 28%), infratentorially (n=9; 8%), extracerebrally (n=12; 11%) or combined (n=9; 8%). In 56 of these 112 children (50%), 14 different side-effects were reported. One hour after anaesthesia, 55 children suffered between one and four side-effects. Neurological side-effects were associated with age > or = 5 years (P < 0.01) or infratentorial pathophysiology (P < 0.01) and abdominal side-effects (P < 0.02), especially nausea (P < 0.001) with age > or = 5 years. CONCLUSIONS: Our findings indicate the need to inform parents of the incidence and variability of side-effects after inhalational anaesthesia for minimally invasive, diagnostic procedures, such as MRI.

Adolescent↗

Estrogen reduces efficacy of mu- but Not kappa-opioid agonist inhibition in response to uterine cervical distension.

BACKGROUND: Although the uterine cervix is a common source of acute and chronic visceral pain in women, there is practically no neurobiological investigation of nociception from this visceral organ. With use of a novel model of uterine cervical distension nociception in rats, the estrogen dependency of opioid agonist-induced inhibition was investigated. METHODS: Sprague Dawley rats were anesthetized with halothane and bilateral ovariectomy was performed, after which placebo or estrogen treatment was administered for 1 week. Animals were reanesthetized and fine metal rods were inserted into the uterine cervix for manual distension. Reflex contraction of the rectus abdominis in response to distension was recorded before and after cumulative dosing with the mu-opioid agonist morphine and the kappa-opioid agonist (-)U50488. RESULTS: Uterine cervical distension increased reflex abdominal muscle contraction with a threshold of 75 g, regardless of estrogen treatment. Morphine and (-)U50488 reduced the reflex response to cervical distension in a dose-dependent manner. Estrogen reduced the inhibitory effect of morphine but not that of (-)U50488. CONCLUSIONS: It has been suggested that mu-opioid agonists are less potent in females than males, whereas kappa-opioid agonists are more potent in females than males. These data suggest that estrogen may influence the action of opioids, at least against visceral pain, which may explain this sex difference. In addition, these data suggest that kappa-opioid agonists may be effective in the treatment of pain originating from the uterine cervix, regardless of estrogen status.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Pharmacology of opioid inhibition to noxious uterine cervical distension.

BACKGROUND: Reflex abdominal muscle contraction elicited by colorectal distension in male rats is inhibited by mu- and kappa-opioid receptor agonists and sites of action and receptor subtypes have been probed. The authors examined the pharmacology of opioid agonist inhibition in visceral pain related to the uterine cervix, the source of labor pain. METHODS: Ovariectomized female rats were anesthetized with halothane, and metal rods inserted in the uterine cervix through a small midline laparotomy. After a period of stabilization the cervix was distended by manual separation of the rods, using stimuli of 25-100 g, and reflex rectus abdominis electromyographic activity was recorded. After determining the stimulus response relationship, we tested inhibition of reflex activity by -U50,488 and morphine and their reversal with norbinaltorphimine, or with naltrexone and methyl-naltrexone, respectively. RESULTS: Cervical distension produced a stimulus-dependent increase in electromyographic activity, with a threshold of 25 g. Morphine and -U50,488 produced dose-dependent inhibition of the reflex activity. Log linear regression analysis demonstrated an ID50 of 0.03 for morphine, and of 0.05 mg/kg for -U50,488. These effects were reversed by naltrexone, but not by methylnaltrexone or norbinaltorphimine. CONCLUSIONS: These data suggest that mu- and kappa-opioid receptor agonists effectively inhibit responses to acute uterine cervical stimulation. Lack of reversal by norbinaltorphimine further supports evidence of a novel kappa-opioid receptor by visceral afferents. Lack of morphine reversal by methylnaltrexone suggests central (spinal or supraspinal) sites of action for inhibition of this visceral noxious stimulus.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗