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Biomedical subjects

S F Atweh

Publications and source records attributed to S F Atweh.

At least 37 records · Page 2Linked to original sources
PubMed1997

Acute and neonatal capsaicin treatment inhibit jejunal amino acid absorption through a Na+-dependent mechanism.

It has recently been shown that capsaicin inhibits alanine absorption in rat jejunum via mechanisms that involve intestinal capsaicin-sensitive primary afferent (CSPA) fibers. This study provides further evidence that the effect of capsaicin is neurally mediated and demonstrates that CSPA fibers regulate Na+-dependent amino acid absorption. In vivo, basal alanine absorption in rats neonatally treated with capsaicin was reduced by 35% below control. Furthermore, intraluminal perfusion of 400 microM capsaicin reduced jejunal alanine absorption by 31% in sham rats but had no significant effect in rats neonatally treated with capsaicin. In vitro, capsaicin significantly reduced uptake of alanine and proline by jejunal strips but had no effect on uptake of lysine. Tetrodotoxin (0.2 microM) partially blocked the effects of capsaicin but did not itself affect alanine absorption. Capsaicin reduced unidirectional mucosal-to-serosal alanine (1 mM) influx by 33%, an effect that becomes significant after 5 min of preincubation with capsaicin. Neonatal capsaicin treatment reduced basal alanine influx in jejunal strips by 37%; however, preincubation of these strips with capsaicin had no significant effect. Kinetic analysis of alanine steady-state uptake and influx by jejunal strips incubated with capsaicin revealed that capsaicin reduced the Na+-dependent component of alanine influx into intestinal epithelial cells. Long-term sensory denervation by capsaicin also decreased the Na+-dependent component of alanine absorption. These data suggest that intestinal capsaicin-sensitive primary afferent fibers regulate Na+-dependent amino acid absorption.

Alanine↗
PubMed1997

Effects of various analgesic and anti-inflammatory drugs on endotoxin-induced hyperalgesia in rats and mice.

A new model of endotoxin (ET)-induced hyperalgesia has been used to test the effects of four classes of drugs in rats and mice. Hyperalgesia was assessed by paw pressure (PP), hot plate (HP) and tail flick (TF) tests. Each drug was injected intraperitoneally 24 and 12 h before ET injection and just before each pain test at 3, 6, 9 and 24 h after ET injection. At the dosages used, acetaminophen and dexamethasone were the most effective in reducing PP hyperalgesia and least effective on TF hyperalgesia, while indometacin and morphine produced their main effect on TF hyperalgesia. The four drugs were about equally effective in reversing HP hyperalgesia. We conclude that ET hyperalgesia is mediated by both prostaglandin-sensitive and prostaglandin-independent mechanisms.

Acetaminophen↗
PubMed1996

Endotoxin-induced local inflammation and hyperalgesia in rats and mice: a new model for inflammatory pain.

Lipopolysaccharide, also known as endotoxin (ET), is a major constituent of the outer membrane of the cell wall of most gram negative bacteria. ET is known to cause a number of pathophysiological changes associated with illness including inflammatory pain. The aim of this study is to characterize the peripheral hyperalgesia induced by ET in rats and mice. Different groups of rats and mice received different doses of ET ranging from 0.6 microgram to 40 micrograms dissolved in 50 microliters saline and injected in the plantar area of the left hind legs. All animals were subjected to tail immersion (TF), hot plate (HP) and paw pressure (PP) tests, 2-3 days prior to ET injection and during the following 1-2 days. ET injections produced a dose-dependent decrease in the latencies of the HP and PP tests of the injected leg reaching a maximum decrease of 50-60% of the control with 20-40 micrograms ET at 9 h (rats) and 24 h (mice) after the injection. Almost complete recovery was observed after 24 h in rats and 48 h in mice. TF latencies showed a less but a significant decrease while PP of the opposite leg and all tests in saline-injected animals did not elicit significant variations and served as additional controls. Our results indicate that the use of ET-produced hyperalgesia is a valid model for local and reversible inflammatory pain, with minimal distress to the animal. This model can also be used to study the efficacy of various anti-inflammatory and analgesic drugs and the molecular mechanisms of inflammation induced by bacterial invasion.

Animals↗
PubMed1996

Effects of cerebral cortical and striatal lesions on autotomy following peripheral neurectomy in rats.

Peripheral nerve lesions have been reported to produce deafferentation pain and persistent changes at various levels of the central nervous system. Using autotomy in rats following leg denervation, as a model for deafferentation pain, we studied the effect of various cerebral lesions on this abnormal behavior. Under deep anesthesia, rats were subjected either to massive hemidecortication or to subtotal hemispherectomy (involving parts of basal ganglia and limbic areas), which was followed 1 week later by a denervation of the ipsilateral or contralateral leg. Hemidecortication significantly delayed autotomy from 7.8 +/- 2.8 to 25.6 +/- 2.1 days without reducing its incidence, whereas hemispherectomy abolished the incidence of autotomy in the contralaterally denervated leg and delayed its onset from 7.8 +/- 2.8 to 34 +/- 6.1 days and decreased its incidence (from 100% to 60%) in the ipsilaterally denervated leg. Chemical lesions of the neostriatum produced similar effects on autotomy to those produced by hemispherectomy. Hemispherectomized and striatum-lesioned rats that failed to elicit autotomy in the contralaterally denervated leg were subjected after 7 weeks to denervation of the ipsilateral leg. Sixty to seventy percent of these rats showed autotomy and in half of them the attack was directed simultaneously to both legs. These results suggest an involvement of the cerebral cortex and a stronger contribution of subcortical structures (like striatum and limbic system) in the processing of nociceptive information.

Animals↗
PubMed1995

Effects of intravenous vasoactive intestinal peptide injection on jejunal alanine absorption and gastric acid secretion in rats.

The effect of intravenous vasoactive intestinal polypeptide (VIP) injection on jejunal L-alanine absorption and gastric acid secretion in the rat was investigated. Continuous intravenous VIP infusion (11.2 ng/kg per min) throughout the experimental period (160 min) produced 60% decrease in alanine absorption and 40% decrease in gastric acid secretion during the second hour of the experiment. Subdiaphragmatic vagotomy reduced alanine absorption to 91% (P > 0.05) and 71.3% (P < 0.05) of control value during the first and second hours of perfusion, respectively. VIP infusion following vagotomy elicited a reduced effect when compared to that produced by similar injections in normal rats. Gastric secretion in vagotomized rats was reduced by 40% (P < 0.05) below control. VIP infusion in vagotomized rats exerted a significant decrease (P < 0.05) of gastric acid secretion. Moreover, water absorption was decreased by almost 10% (P < 0.05) after i.v. injection of VIP and was increased by 20-24% above control value following vagotomy. However, i.v. administration of VIP following vagotomy did not elicit any further change in water absorption. It can be concluded that VIP inhibits alanine absorption and gastric acid secretion in the rat and that these inhibitory effects might be partially mediated by the vagus nerve.

Alanine↗
PubMed1995

Effects of intracerebral injections of VIP on jejunal alanine absorption and gastric acid secretion in rats.

The effects of intracerebral injections of VIP on jejunal alanine absorption and gastric acid secretion, and its association with vagal outflow were examined in Sprague-Dawley rats. Intracerebroventricular injection of VIP (2 ng) decreased significantly (P < 0.05) alanine absorption across the jejunum, whereas similar injections in vagotomized rats did not show further decrease in absorption beyond that noticed by vagotomy only. Moreover, VIP injected in the Nucleus Tractus Solitarius-Dorsal Motor Nucleus (NTS-DMN) complex (1 ng) produced also a significant inhibition of Ala absorption which was reduced but remained significant (P < 0.05) after vagotomy. Water movement was not affected by VIP injection in the lateral ventricle, while VIP injections in the NTS-DMN inhibited significantly (P < 0.05) jejunal water absorption by 10-12%. Vagotomy increased water absorption by 15-20% above control (P < 0.05) which was not altered by injecting VIP in the NTS-DMN complex. On the other hand, VIP injection in the NTS-DMN produced a 25.7% increase in gastric acid output in the first hour of the experiment followed by a non-significant decrease (P > 0.05) in the second hour. Same injections done in vagotomized animals produced similar effects to those elicited by vagotomy only. It can be suggested that NTS-DMN complex could be a site of action of VIP since injection of VIP in it produced a more pronounced inhibitory effect on water and Ala absorption than that produced by VIP injection in the LV. These effects were reduced or abolished by vagotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1995

Involvement of capsaicin-sensitive primary afferent fibers in regulation of jejunal alanine absorption.

Capsaicin-sensitive primary afferent fibers (CSPA) in the small intestine regulate many functions through the release of peptides and neurotransmitters. This study was undertaken to assess the role of CSPA in the regulation of jejunal alanine absorption in the rat. In a series of in vivo experiments, the effects of the sensory neurotoxin capsaicin on small intestinal alanine absorption were evaluated. In vitro experiments were also done to study its effects on alanine uptake by isolated jejunal strips and mucosal scrapings. Jejunal alanine absorption was reduced by 27% when capsaicin (160 and 800 microM) was perfused intraluminally and by 21% when it was applied topically to the cervical vagi. On the other hand, bilateral cervical vagotomy and reversible block of vagal CSPA increased alanine absorption by 29 and 41%, respectively. In vitro, capsaicin reduced alanine uptake by intestinal strips in a dose-dependent manner. Maximal inhibition (36.5%) occurred at 400 microM with the mean ineffective concentration at 87 microM. Alanine uptake by jejunal mucosal scrapings, however, was decreased only by 6.7% when incubated with 1,600 microM capsaicin. These data suggest that vagal CSPA exerts a tonic inhibitory effect on alanine absorption and that capsaicin's inhibitory effect on alanine absorption is mediated largely by the capsaicin-sensitive afferent fibers.

Absorption↗
PubMed1993

Explosive autotomy induced by simultaneous dorsal column lesion and limb denervation: a possible model for acute deafferentation pain.

We report on a new "explosive" form of self-mutilation behavior (autotomy) characterized by rapid onset (1-2 days), short duration (1-2 days), and unpredictable progression. The possible neural mechanism(s) underlying this novel behavior were examined in rats by combining at varying time intervals one leg denervation with a lesion to the dorsal columns (DC lesion) or to a dorsolateral funiculus (DLF lesion). DC lesion, followed immediately by leg denervation, resulted in explosive autotomy in 62% of the rats and regular autotomy in 25% of the rats. Regular autotomy was characterized by slow onset (2-3 weeks), prolonged duration (2-3 weeks), and stereotyped progression from distal to proximal parts of the leg. DC lesion, followed 1 week later by leg denervation, resulted in regular autotomy in 71% of the rats which was not different from autotomy resulting from denervation alone. DC lesion preceded 1 week earlier by leg denervation resulted in slightly accelerated regular autotomy in 77% of the rats. Simultaneous DC lesion and leg denervation immediately preceded by application of a local anesthetic (4% procaine) for 30 or 60 min to the exposed lumbar spinal cord resulted in regular autotomy in all rats. All rats in a sham group, in which the procaine was replaced by normal saline, exhibited explosive autotomy. DLF lesion, followed immediately by leg denervation, resulted in accelerated regular autotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1993

The role of previous nociceptive input in development of autotomy following cordotomy.

Intractable pains have been described after surgical or accidental lesions in the peripheral or central nervous system. The possible contribution of antecedent injury to the appearance of these pains was examined in an animal model for chronic pain which involved observing self-mutilation or autotomy behavior in rats. Various combinations of previous injury, selective spinal cut, and peripheral denervation were carried out on rats. Injuries ranged from mild to moderate and were produced by nociceptive stimuli from formaldehyde injection, induced local arthritis, or hot water application. Selective spinal cuts included either a dorsal column (DC), a dorsal quadrant which included a DC and a dorsolateral funiculus, an anterolateral column (ALC), or a hemisection. In rats without prior exposure to injury the various types of spinal cuts were not associated with any autotomy. In rats with prior exposure to formaldehyde injection, autotomy was associated only with spinal cuts that involved the ALC. In an otherwise similar group of rats but with prior induction of local arthritis, a stronger association of ALC lesion and autotomy was observed. In an earlier study, rats with ALC lesion prior to denervation showed reduced autotomy. In this study, we demonstrated that in rats with previous exposure to heat injury, an ALC lesion was strongly associated with autotomy. Autotomy was absent, however, in rats with heat injury only. These findings strongly suggest that pain resulting from previous exposure to injury produces a memory trace in the central nervous system which can account for the phantom pains encountered in various clinical conditions.

Animals↗
PubMed1990

Effects of lesions in the anterolateral columns and dorsolateral funiculi on self-mutilation behavior in rats.

The possible role of the anterolateral columns (ALCs) and dorsolateral funiculi (DLF) in pain mechanisms was examined from the effects of lesions in these tracts (alone or combined) on tests for chronic deafferentation pain (autotomy) in rats. Spinal lesions alone (i.e., without denervation) in either ALC or DLF or combined DLF-ALC did not lead to any form of self-mutilation behavior. Cervical surgery, without spinal lesion, followed by limb denervation (sham) resulted in similar autotomy characteristics to those observed following limb denervation alone (control). Both results were considered as one set of controls. ALC lesions simultaneous with, or 1-2 weeks prior to limb denervation (ipsilaterally or contralaterally) produced significant delay in onset of autotomy and decrease in percentage of rats showing this behavior. DLF lesions followed by limb denervation produced significant acceleration of onset of autotomy and increase in percentage of rats showing this behavior. Combined DLF-ALC lesions with limb denervation produced intermediate effects between those observed following either ALC or DLF lesions alone. These results give further support to the concept that autotomy is related to rostral transmission of nociceptive information and that a spino-bulbo-spinal inhibitory loop involving the DLF and ALC is triggered by chronic deafferentation pain.

Animals↗
PubMed1989

Dorsal column input to cochlear neurons in decerebrate-decerebellate cats.

In decerebrate-decerebellate cats with cervical spinal cuts sparing only the dorsal columns (DCs), activation of one DC modulates sound-evoked discharges of neurons in both dorsal cochlear nuclei. In a sample of 50 neurons, 34% were excited or facilitated, 12% were inhibited and 54% were not affected by DC stimulation. This modulation appears to be mediated through direct projections from the dorsal column nuclei to the dorsal cochlear nuclei.

Acoustic Stimulation↗
PubMed1986

Prolonged discharge of wide-dynamic-range spinal neurons evoked by formaldehyde injected in their cutaneous receptive fields.

In decerebrate, unanesthetized cats, subcutaneous injection of formaldehyde solutions (0.05 ml, 2.5%) in the receptive fields of spinal wide-dynamic-range neurons elicited an immediate and continuous discharge or burst activity in the neurons that lasted 10 to 55 min. This discharge was reduced by conditioning stimulation of the medial raphe nucleus and was completely abolished by morphine (3 mg/kg, i.v.). Low-threshold cutaneous mechanoreceptive neurons in the dorsal horn and dorsal column nuclei did not show a sustained response.

Animals↗
PubMed1985

Inhibition of nociceptive evoked activity in spinal neurons through a dorsal column-brainstem-spinal loop.

In decerebrate-decerebellate cats, dorsal column stimulation (DCst), rostral to bilateral dorsal column cuts, inhibited dorsal horn neurons discharging to various types of nociceptive stimuli. Similar inhibitory effects were observed from conditioning nucleus raphe magnus stimulation. Activation of this dorsal column-brainstem-spinal loop could be part of an important supraspinal "gating' system to account for the alleviation of pain both by DCst and peripheral nerve stimulation in man.

Animals↗
PubMed1984

A cholinergic receptor site on murine lymphocytes with novel binding characteristics.

To further analyze functionally important cholinergic receptors on lymphocytes, we studied the binding of the muscarinic antagonist Quinuclidinyl benzilate (QNB) to murine splenic lymphocytes. Studies of displacement of [3H]QNB by unlabeled QNB on lymphocytes revealed at least two binding sites. Scatchard analysis of equilibrium binding isotherms also distinguished two sites with apparent Kds of 480 nM and 16 microM. There was greater specific QNB binding to B cell-enriched lymphocyte fractions than to T cell fractions. Lymphocyte binding demonstrated temperature-dependent dissociability, and specific binding occurred on isolated lymphocyte membranes as well. Both muscarinic and nicotinic ligands competed for QNB binding to lymphocytes with low and nearly equal affinity. Therefore, QNB binding sites on lymphocytes appear to be of low affinity and of mixed muscarinic and nicotinic character.

Animals↗