Biomedical subjects

X J Xu

Publications and source records attributed to X J Xu.

At least 37 records · Page 2Linked to original sources

PubMed2000

The effect of intrathecal endomorphin-2 on the flexor reflex in normal, inflamed and axotomized rats: reduced effect in rats with autotomy.

Endomorphin-2, a newly discovered endogenous opioid peptide and agonist at the mu-opioid receptor, was injected intrathecally in normal rats and animals with unilateral peripheral inflammation or sciatic nerve section and its effect on the nociceptive flexor reflex was analysed. In normal rats, intrathecal endomorphin-2 induced a strong and dose-dependent depression of the reflex, which was naloxone-reversible. The effect of intrathecal endomorphin-2 was fairly brief, lasting for about 20-30 min at the highest dose, 4 microg. The effect of endomorphin-2 in inflamed rats was not significantly different from that in normals. After nerve section some rats developed autotomy behavior. In these rats endomorphin-2 had significantly reduced effect. However, the reflex depressive effect of intrathecal endomorphin-2 was unchanged in axotomized rats without autotomy. It is suggested that intrathecal endomorphin-2 has antinociceptive effect in the rat spinal cord under normal and inflammatory conditions. After peripheral nerve injury the sensitivity to endmorphin-2 may be reduced in rats that exhibit ongoing neuropathic pain-like behaviors.

Analgesics, Opioid↗

PubMed2000

Marked enhancement of anti-allodynic effect by combined intrathecal administration of the adenosine A1-receptor agonist R-phenylisopropyladenosine and morphine in a rat model of central pain.

BACKGROUND: There is often no satisfactory treatment for chronic pain after spinal cord injury. We have previously reported that intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) or the opioid morphine has anti-allodynic effects in a model of presumed chronic central pain after photochemically induced spinal cord injury in rats. In the present study, we set out to investigate the possible interaction between i.t. R-PIA and morphine in spinally injured rats. METHODS: Sprague-Dawley rats displaying allodynia-like behaviors to mechanical and cold stimuli after photochemically induced spinal cord injury with minor motor deficits were used. R-PIA and morphine, either alone or in combination, were administered i.t. through an implanted catheter to lumbar spinal cord. RESULTS: Cumulative doses of R-PIA or morphine dose-dependently reduced the mechanical allodynia-like behavior, with a threshold of 1 nmol and 1.5 nmol, respectively. When co-administrated, R-PIA and morphine produced marked suppression of mechanical allodynia at doses of 5 pmol and 7.5 pmol, respectively. The effect of i.t. co-administration of R-PIA and morphine on cold allodynia was comparable to i.t. R-PIA alone. The combination of R-PIA and morphine did not increase adverse effects such as motor deficits in comparison to either drug alone. CONCLUSION: These results demonstrate a supra-additive interaction between the adenosine A1-receptor agonist R-PIA and morphine to reduce mechanical allodynia-like behavior in rats with chronic spinal cord injury. The combination of R-PIA and morphine administered spinally may be superior to R-PIA or morphine alone for treating such pain.

Analgesics, Opioid↗

PubMed2000

Photochemically-induced ischemic injury of the rat sciatic nerve: a light- and electron microscopic study.

Lesion of presumably ischemic origin of the rat sciatic nerve was induced photochemically by laser irradiation combined with systemic administration of a photosensitizing organic dye, erythrosin B. We have studied the pathologic features of the nerve after the photochemical insult with light- and electronmicroscopy and related them to behavioral signs of neuropathic pain. At the irradiated nerve site, occlusion of blood vessels was seen and the vessels were packed with aggregated thrombocytes, fibrins and deformed erythrocytes, supporting the notion that photochemical reaction caused intraneural ischemia. The degree of the nerve injury at the center of irradiation was related to the duration of the laser exposure. Brief irradiation (30 seconds) only caused identifiable injury to myelinated fibers, whereas longer irradiation (2 minutes) caused greater injury to myelinated and unmyelinated fibers, characterized by extensive axonal degeneration and demyelination. The rats irradiated for 2 minutes, but not 30 seconds, exhibited neuropathic pain-like behaviors, expressed as mechanical and cold allodynia. The nerve injury was most severe 7 days after ischemia and regeneration of both myelinated and unmyelinated fibers was observed 3 months later. The nerve caudal to the irradiation exhibited Wallerian degeneration 7 days after the insult, whereas at 10 mm proximal to the irradiation the nerve was largely normal. It is thus concluded that photochemically induced intraneural ischemia caused injury to both myelinated and unmyelinated fibers, with myelinated fibers being more susceptible. However, the development of neuropathic pain-like behaviors may require injury to the unmyelinated fibers.

Animals↗

PubMed2000

Lack of stereoselectivity for the antiallodynic effect of mexiletine in spinally injured rats.

Systemically administered mexiletine, an antiarrhythmic, has been shown to also possess analgesic properties in some conditions of neuropathic pain. It has been suggested that the analgesic effect of mexiletine may be derived from the action of one of its optical isomers, (+)(S)-mexiletine. In the present study, we have compared the effects of systemic (-)-(R)- and (+)-(S)-mexiletine, on chronic mechanical allodynia-like behaviour in spinally injured rats, a model of central neuropathic pain in which racemic mexiletine has been shown to be active. I.p. racemic mexiletine as well as (-)-(R)- and (+)(S)-mexiletine at 25 mg/kg all produced significant, but brief, alleviation of mechanical allodynia in a similar fashion as assessed with von-Frey hair elicited vocalization in the spinally injured rats. A slight increase in motor impairment was observed in all three groups which reached statistical significance for the racemic mexiletine and (+)-(S)-mexiletine. Our results suggest that both isomers of mexiletine contribute to the antiallodynic effect in this model of central pain.

Analgesics↗

PubMed2000

Possible effects of the Three Gorges dam on the transmission of Schistosoma japonicum on the Jiang Han plain, China.

The Three Gorges dam, under construction on the Yangtze River in China, might affect the transmission of Schistosoma japonicum on the Jiang Han plain, which is downstream of the dam. To study this possibility, the prevalence of schistosomiasis was investigated in relation to a range of malacological, hydrological and meteorological factors. The general water level in the Yangzte over a year had a marked effect on the distribution of the intermediate host (Oncomelania hupensis) and the prevalence of human schistosomiasis in that year. Disease prevalence showed significant correlations with the density of the snail hosts, the level of the water table, annual rainfall, yearly evaporation, and altitude. Once the dam is complete, the flow of water downstream will probably be maintained at a level between those currently occurring in flood and dry weather, and this may have implications for schistosome transmission. Systematic monitoring is necessary to investigate the impact of the environmental changes brought about by the dam on transmission.

Altitude↗

PubMed1999

Cholecystokinin/opioid interactions.

Cholecystokinin (CCK) acts as an anti-opioid peptide. The mechanisms of CCK-opioid interaction under normal and pathological conditions were examined with various techniques. Nerve injury induces upregulation of CCK mRNA and CCK2 receptors in sensory neurons. The involvement of CCK in spinal nociception in normal and axotomized rats was examined. The CCK2 receptor antagonist CI-988 did not reduce spinal hyperexcitability following repetitive C-fiber stimulation in normal or axotomized rats, suggesting that CCK is probably not released from injured primary afferents. With in vivo microdialysis intravenous (i.v.) or intrathecal (i.t.) morphine increased the extracellular level of CCK in the dorsal horn in a naloxone reversible manner. Morphine also released CCK after axotomy, but not during carrageenan-induced inflammation. In contrast, K(+)-stimulation failed to increase extracellular levels of CCK in axotomized rats, but did so in inflamed rats. Double-coloured immunofluorescence technique revealed partial co-localization between CCK-like immunoreactivity (LI) and mu-opioid receptor (MOR)-LI in superficial dorsal horn neurons. The presence of MOR in CCK containing neurons suggests a possible direct influence of opioids on CCK release in the spinal cord. Axotomy, but not inflammation, induced a moderate decrease in CCK- and MOR-LI in the dorsal horn. I.v. morphine further temporarily reduced CCK- and MOR-LIs in axotomized, but not in normal or inflamed, rats. While the effect of morphine on CCK-LI can be interpreted as the result of increased CCK release, the effect on MOR-LI may be related to changes in the microenvironment of the dorsal horn induced by nerve injury.

Animals↗

PubMed1999

Effects of intrathecal nocistatin on the flexor reflex and its interaction with orphanin FQ nociceptin.

We studied the effects of intrathecal (i.t.) nocistatin, a peptide identified from the precursor of orphanin FQ/nociceptin (OFQ) on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats and its interaction with i.t. OFQ. Nocistatin induced a moderate, non-dose-dependent facilitation of the flexor reflex without producing reflex depression whereas i.t. OFQ induced a biphasic dose-dependent facilitatory and inhibitory effect. The facilitatory effect of low dose (0.55 pmol) OFQ was significantly increased by nocistatin. On the other hand, the duration, but not magnitude, of reflex depression induced by a high (550 pmol) dose of OFQ was significantly shortened by 5.5 nmol nocistatin. Thus, nocistatin interacts with OFQ in a complex fashion, increasing excitation and reducing inhibition. No evidence was obtained for an antinociceptive effect of nocistatin in rat spinal cord.

Animals↗

PubMed1999

Intrathecal adenosine does not relieve allodynia-like behavior in spinally injured rats.

The intrathecal (i.t.) administration of the adenosine A1-receptor agonist R-phenylisopropyl-adenosine (R-PIA) reduced pain-related behaviors after peripheral nerve or spinal cord injury in rats. The endogenous ligand adenosine is clinically available and has been tested i.t. as an analgesic. Thus, we set out to investigate whether i.t. adenosine could reduce allodynia in a model of central pain in spinally injured rats. I.t. adenosine did not reduce mechanical and cold allodynia-like behaviors at doses of 10, 100 and 187 nmol, whereas i.t. R-PIA at 10 nmol markedly alleviated allodynia in the same animals. The lack of effect by exogenous adenosine may be due to pharmacokinetic or pharmacodynamic reasons. Alternatively, adenosine may have reduced affinity and selectivity towards the A1-receptors which may be important for the antiallodynic effect.

Adenosine↗

PubMed1999

The effect of intrathecal selective agonists of Y1 and Y2 neuropeptide Y receptors on the flexor reflex in normal and axotomized rats.

We have examined the effects of intrathecal (i.t.) administration of [Leu31,Pro34]-neuropeptide Y (NPY) or NPY-(13-36), selective agonists of NPY Y1 or Y2 receptors, respectively, on the excitability of the flexor reflex in normal rats and after unilateral transection of the sciatic nerve. In rats with intact and sectioned sciatic nerves, i.t. [Leu31,Pro34]-NPY induced a similar biphasic effect on the flexor reflex with facilitation at low doses and facilitation followed by depression at high doses. In contrast, i.t. NPY-(13-36) only facilitated the flexor reflex in normal rats, and at high dose it caused ongoing discharges in the electromyogram. NPY-(13-36) caused dose-dependent depression of the flexor reflex in rats after sciatic nerve transection, in addition to its facilitatory effect. Topical application of [Leu31,Pro34]-NPY or NPY-(13-36) caused a moderate and brief reduction in spinal cord blood flow. No difference was noted between the vasoconstrictive effect of [Leu31,Pro34]-NPY and NPY-(13-36). It is suggested that activation of Y1 receptors may be primarily responsible for the reflex depressive effect of i.t. neuropeptide Y in rats with intact sciatic nerves, whereas both Y1 and Y2 receptors may be involved in mediating the depressive effect of NPY after axotomy.

Animals↗

PubMed1999

Effects of intrathecal orphanin FQ on a flexor reflex in the rat after inflammation or peripheral nerve section.

We examined the effects of intrathecal orphanin FQ, the endogenous ligand for the orphan opioid-like receptor, on the hamstring nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats after carrageenan-induced inflammation or unilateral sciatic nerve transection. As described previously [Xu, X.-J., Hao, J.-X., Wiesenfeld-Hallin, Z., 1996. Orphanin FQ or antiorphanin FQ: potent spinal antinociceptive effect of orphanin FQ/orphanin FQ in the rat. NeuroReport 7, 2092-2094.], intrathecal orphanin FQ induced a dose-dependent depression of the flexor reflex with a ED50 of 965 ng. Initial reflex facilitation was noted in some experiments at lower doses (10 or 100 ng). A similar bi-phasic response pattern to intrathecal orphanin FQ was observed in experiments conducted in inflamed or axotomized rats. However, the magnitude of the initial reflex facilitation was significantly increased in inflamed rats compared to normals whereas the duration of reflex depression was significantly shortened. The ED50 for reflex depression was 2.4 jig for inflamed rats. In contrast, axotomy did not significantly alter the facilitatory and depressive effect of orphanin FQ with ED50 for reflex depression being 374 ng. These results confirmed an inhibitory action of orphanin FQ on spinal nociception in rats. It is suggested that the effect of orphanin FQ may be modulated by inflammation and nerve injury. In particular, unlike morphine, there seems to be no reduction in the effect of spinal orphanin FQ in inducing antinociception after peripheral nerve axotomy.

Animals↗

PubMed1999

Genetic differences in the antinociceptive effect of morphine and its potentiation by dextromethorphan in rats.

The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist dextromethorphan on morphine-induced antinociception was studied with the hot plate test in Sprague-Dawley (SD), Wistar-Kyoto (WK), Spontaneously Hypertensive (SHR) and Dark-Agouti (DA) rats. Subcutaneous morphine at 5 mg/kg induced significant antinociception in all four rats strains. Subcutaneous dextromethorphan at 15 and 45 mg/kg, but not 5 mg/kg, significantly and dose-dependently potentiated morphine-induced antinociception in SDs, WKs and SHRs, but not in DAs. In SHRs and DAs the antinociceptive effect of morphine was followed by prolonged hyperalgesia, which was reduced (SHRs) or abolished (DAs) by dextromethorphan. These results suggest that there are significant differences among rat strains in their response to morphine and in the ability of dextromethorphan to potentiate morphine-induced antinociception. These differences are possibly of genetic origin. Moreover, these data show that morphine, at least in some strains of rats, induced a delayed and NMDA receptor-dependent hyperalgesic response, supporting the notion that administration of opiates may activate NMDA receptors, leading to reduced antinociceptive effect and the development of hyperalgesia.

Animals↗

PubMed1999

Molecular characterization of cDNA for phospholipase A2-activating protein.

A phospholipase A2-activating protein (PLAP) cDNA was cloned and sequenced from a human monocyte cDNA library, and expressed as a histidine-tagged fusion protein. The DNA-deduced aa sequence of human PLAP was 80,826 Da; however, SDS-PAGE analysis revealed a 72-74 kDa protein which matched the size of native PLAP from human monocytes. Anti-sense plap oligonucleotide blocked cholera toxin-induced release of 3H-labeled arachidonic acid from cells, indicating a potential role for PLAP in regulating phospholipase A2 activity.

Amino Acid Sequence↗

PubMed1999

Spinal cord ischemia reduces mu-opioid receptors in rats: correlation with morphine insensitivity.

The present study examined the effects of spinal cord ischemia on the expression of mu-opioid receptors in rat dorsal spinal cord and the effects of intrathecal (i.t.) morphine on the acute mechanical allodynia that developed after spinal ischemia. The mechanical allodynia was not significantly alleviated by up to 10 microg i.t. morphine, a dose which caused strong antinociception in the tail flick test. Immunohistochemical staining demonstrated that the level of mu-opioid receptor expression in the dorsal horn of spinal cord segments receiving input from the allodynic skin was markedly reduced 2 days after ischemia, when the rats were allodynic. The results indicate that spinal cord ischemia reduces the expression of mu-opioid receptors in rat dorsal horn, which may be one of the underlying mechanisms of morphine insensitivity for treating acute allodynia after spinal ischemia.

Analgesics, Opioid↗

PubMed1999

Spontaneous T-cell proliferation in the non-obese diabetic mouse to a peptide from the unique class II MHC molecule, I-Ag7, which is also protective against the development of autoimmune diabetes.

AIMS/HYPOTHESIS: Major histocompatibility complex class II molecules present antigenic peptides to T-cells and have an important role in T-cell thymic education. The mechanism by which major histocompatibility complex alleles confer a high genetic risk for autoimmune diabetes is not known. One hypothesis is that during positive thymic selection, the peripheral T-cell repertoire is modelled by major histocompatibility complex-restricted presentation of self major histocompatibility complex molecule-derived peptides, some of which mimic tissue autoantigens. The sequence similarity between a known T-cell epitope of glutamic acid decarboxylase-65, 509:VPPSLRTLED and the non-obese diabetic mouse class II major histocompatibility complex molecule I-Ag7 86:VPTSLRRLEQ is consistent with this. METHODS: We measured spontaneous proliferation of peripheral T-cells from non-obese diabetic mice and other, non-diabetes-prone strains, to the I-Ag7 86-101 and glutamic acid decarboxylase-65(509-524) peptides, binding of these peptides to intact I-Ag7 and assessed the effect of tolerance induction on diabetes development, by injecting young non-obese diabetic mice with high doses of peptide. RESULTS: T-cells from non-obese diabetic, but not other mice strains, spontaneously proliferate to the I-Ag7 86-101 and glutamic acid decarboxylase-65(509-524) peptides, but not control peptides. Both test peptides bind I-Ag7. Tolerance induction prolongs diabetes-free survival in non-obese diabetic mice when either the I-Ag7 86-101 or glutamic acid decarboxylase-65(509-524) peptide, but not control peptide, is used. CONCLUSION/INTERPRETATION: A peptide from the unique class II major histocompatibility complex, diabetes-susceptibility molecule, I-Ag7, presented by I-Ag7 is a target of T-cell responses in diabetes-prone nonobese diabetic mice and tolerance induction against the peptide offers appreciable protection against the development of diabetes.

Amino Acid Sequence↗

PubMed1999

Effects of intrathecal morphine, clonidine and baclofen on allodynia after partial sciatic nerve injury in the rat.

BACKGROUND: Increased response to mechanical or cold stimulation of hind paws was observed in rats with partial sciatic nerve injury as a result of photochemically induced ischemia. The present study examined the effects of intrathecal morphine, clonidine and baclofen on the allodynia-like responses. METHODS: The left sciatic nerves of rats were irradiated for 2 min with an argon ion laser under chloral hydrate anesthesia. The threshold of paw withdrawal to mechanical stimulation was determined with a series of monofilaments (von Frey hairs). The response to cold stimulation was tested by spraying ethyl chloride on the plantar surface of the paw. When rats were exhibiting stable mechanical and cold allodynia-like behaviors after nerve injury, the effects of i.t. morphine (1, 2, 7 microg), clonidine (1, 2, 7 microg) and baclofen (0.1, 0.2, 0.7, 9 microg) in a cumulative dose regime were investigated. RESULTS: Intrathecal morphine dose-dependently alleviated the mechanical and cold allodynia without inducing motor impairment or sedation. Intrathecal clonidine did not alter the response of hind paws to mechanical stimulation, but reduced the cold allodynia. Intrathecal baclofen reduced the responses of rats to mechanical stimulation only at doses that also induced profound motor deficits. CONCLUSIONS: The present data suggest that intrathecal morphine, and to some extent clonidine, but not baclofen, alleviated the abnormal pain-related behaviors in this new rat model of partial peripheral nerve injury. Differences in the pharmacological profile between the present model and other models of peripheral nerve injury are discussed.

Analgesics↗

PubMed1999

Intrathecal galanin alleviates allodynia-like behaviour in rats after partial peripheral nerve injury.

We have previously suggested that the neuropeptides galanin and galanin message-associated peptide (GMAP) may have an inhibitory role in spinal nociception. The present study examined the effects of intrathecal (i.t.) administration of these two peptides on allodynia-like behaviours in response to mechanical and cold stimulation in rats after photochemically induced ischaemic peripheral nerve injury. I.t. galanin significantly alleviated the mechanical- and cold-allodynia-like behaviours in nerve injured rats, and was not associated with motor impairment or sedation. I.t. GMAP relieved mechanical allodynia much less than galanin. I.t. M-35, a high-affinity galanin receptor antagonist, did not significantly alter the response of the rats to mechanical or cold stimulation. At 1 or 2 weeks postinjury, around 15% of dorsal root ganglion (DRG) neuron profiles showed galanin-like immunoreactivity. These profiles were mostly small sized. Although the number of galanin positive cells was thus increased in the DRG in the present model, the increase was substantially less than after complete sciatic nerve section, as previously shown. The present results showed that spinal administration of galanin inhibited some abnormal pain-like behaviours in rats after partial peripheral nerve injury. These results further support an inhibitory function for galanin in nociception. However, endogenous galanin may not play a significant role in suppressing nociceptive input after partial ischaemic peripheral nerve injury, as the upregulation of galanin is moderate.

Animals↗

PubMed1999

Impact of environmental change and schistosomiasis transmission in the middle reaches of the Yangtze River following the Three Gorges construction project.

With the construction of the Three Gorges high dam on the Yangtze River in China in mind, a serious of ecological environmental factors that might affect the transmission of Schistosoma japonicum in Jian Han Plain were investigated by means of data collection, field surveys and observation in Hubei Province. Several ecological factors including water level of the Yangtze River; riparian water table, annual rainfall and yearly evaporation were investigated in relation to the prevalence of schistosomiasis. The results suggest that after the dam construction, middle water level flows (ie between flood flows and dry-weather flows) will persist in the flood season due to a rise in the water table. The investigation indicated that snail distribution and human schistosomiasis prevalence differed significantly between years which had typically high, middle and low typical water levels in the Yangzte. Moreover, the prevalence of the disease showed a significant linear regression relationship with density of snail intermediate hosts, water table, annual rainfall, yearly evaporation and ground altitude in the survey area. Systematic and careful monitoring and surveillance is necessary to investigate the impact of the environmental changes brought about by the dam construction on schistosomiasis transmission.

Animals↗

PubMed1998

Galanin in somatosensory function.

Galanin-like immunoreactivity and galanin receptors are found in dorsal root ganglion (DRG) cells and in dorsal horn interneurons, suggesting that this neuropeptide may have a role in sensory transmission and modulation at the spinal level. Expression of galanin or galanin receptors in the DRG and spinal cord are altered, sometimes in a dramatic fashion, by peripheral nerve injury or inflammation. Under normal conditions, galanin occurs in a small population of primary sensory neurons as well as in spinal interneurons. However, following peripheral nerve injury or inflammation, expression of galanin in primary afferents and spinal cord is upregulated. We examined the role of galanin in spinal processing of nociceptive information under normal and pathologic conditions in a large series of electrophysiologic and behavioral studies. Results suggest that under normal conditions galanin exerts tonic inhibition of nociceptive input to the central nervous system. After peripheral nerve injury the inhibitory control exerted by endogenous galanin, probably released from DRG neurons, is increased. During inflammation, galanin presumably released from dorsal horn interneurons also exerts an inhibitory function. Thus, stable galanin agonists may be useful in the treatment of inflammatory and neuropathic pain.

Animals↗