Biomedical subjects

Xiao-Jun Xu

Publications and source records attributed to Xiao-Jun Xu.

34 records · Page 2Linked to original sources

PubMed2003

The very-high-efficacy 5-HT1A receptor agonist, F 13640, preempts the development of allodynia-like behaviors in rats with spinal cord injury.

Central neuropathic pain after spinal cord injury (SCI) presents a challenging clinical problem with limited treatment options. [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-([(5-methyl-pyridin-2-ylmethyl)-amino]-methyl)piperidin-1-yl]]-methadone (F 13640) is a recently discovered very-high-efficacy, selective 5-HT1A receptor agonist that produces a remarkably powerful, central analgesia through unprecedented neuroadaptive mechanisms. In a rat model of spinal cord injury pain, we previously found that chronic infusion of F 13640 alleviated pain-like behaviors. Here, we report that infusion of 0.63 mg/day of F 13640 for 8 weeks starting 24 h before the induction of injury significantly attenuates the development of chronic allodynia-like behavior in rats sustaining a photochemically-induced, ischaemic injury of the dorsal laminae of the L3-L5 segments of the spinal cord. Importantly, the preemptive effect of F 13640 persisted for 2 months after treatment was discontinued. The data warrant the study of the possible effects of the early administration of F 13640 in patients sustaining spinal cord injury.

Animals↗

PubMed2003

Flexor reflex excitability in mice lacking galanin receptor galanin-R1.

This study was conducted to examine the excitability of the nociceptive flexor reflex and its sensitization by repetitive stimulation of C-fibers in anesthetized mice that lack the galanin-R1 receptor. Repetitive stimulation of C-fibers induced a gradual increase in reflex magnitude during the stimulation (wind-up), and a subsequent increase in spinal reflex excitability (central sensitization). This occurred in GAL-R1 -/-, GAL-R1 +/-, and +/+ wild-type controls, with no significant differences observed between genotypes. Intrathecal administration of galanin markedly blocked the sensitization following the repetitive stimulation in all three groups. No differences between wild-type or galanin-R1 receptor knockout mice were seen. These results confirm previous studies in rats, showing that intrathecal galanin reduces the central sensitization following wind-up. The present data indicate that this effect is probably mediated by receptors other than GAL-R1.

Analysis of Variance↗

PubMed2003

A comparison of the antinociceptive effects of voltage-activated Na+ channel blockers in two rat models of neuropathic pain.

The pain-relieving effects of various voltage-activated Na(+) channel blockers have been evaluated in two rat models of neuropathic pain; the photochemically induced nerve injury model (Gazelius) and spared nerve injury model. Lidocaine (up to 40 mg/kg, i.p.) and lamotrigine (up to 60 mg/kg, i.p.) had no effect on mechanical or cold allodynia in either model. However, lamotrigine (10, 30 and 60 mg/kg) significantly attenuated mechanical hyperalgesia in the spared nerve injury model, while mexiletine (25 and 37.5 mg/kg, i.p.) attenuated mechanical allodynia in the Gazelius model. Tocainide (50, 75 and 100 mg/kg, i.p.) significantly reduced all types of pain behaviour measured. The present results show that these voltage-activated Na(+) channel blockers have broadly similar antinociceptive effects in these two models of neuropathic pain. They also show that these drugs can have markedly different effects on distinct neuropathic pain-related behaviours within models.

Analgesics↗

PubMed2003

Opioid hyperalgesia and tolerance versus 5-HT1A receptor-mediated inverse tolerance.

In addition to analgesia, opioids also produce paradoxical hyperalgesic effects following acute and chronic treatment. In this article, we review the occurrence of this hyperalgesia under several conditions, and discuss the potential mechanisms and clinical implications. We also review recent evidence that paradoxical analgesia and inverse tolerance induced by stimulation of 5-HT(1A) receptors, which is a mirror image of opioid-induced hyperalgesia and tolerance, might achieve clinically significant analgesia in chronic pain.

Analgesics, Opioid↗

PubMed2003

Reduced spinal cord sensitization to C-fibre stimulation in mice over-expressing galanin.

The neuropeptide galanin may have a role in spinal nociception. In this study, we examined the excitability of the flexor reflex and its sensitization by repetitive stimulation of nociceptive C-fibres in anaesthetized mice that over-express galanin. No difference was seen between over-expressing galanin and wild-type mice in the magnitude of the baseline flexor reflex. Repetitive conditioning stimulation of C-fibres (10 stimuli at 1 Hz) produced a gradual increase in reflex magnitude during the conditioning stimulation (wind-up), as well as an increase in spinal reflex excitability after the termination of the stimulus train (central sensitization) in wild-type mice. Although the wind-up did not differ between over-expressing galanin and wild-type mice, the magnitude of central sensitization was significantly reduced in the over-expressing galanin mice (24 +/- 13% peak increase compared with 164 +/- 65% in the wild-type). Intrathecal administration of M35, a galanin receptor antagonist, markedly enhanced central sensitization in over-expressing galanin mice in association with C-fibre conditioning stimulation, while having no effect in wild-type mice. These results provide further electrophysiological evidence for an inhibitory function of galanin in modulation of central sensitization in response to C-fibre stimulation.

Animals↗

PubMed2003

Animal models of spinal cord injury pain and their implications for pharmacological treatments.

Patients with spinal cord injury often develop chronic pain syndrome, which is difficult to treat. Several animal models of spinal cord injury have been developed in recent years which have significantly advanced our understandings of pathophysiology of this condition. This paper reviews some recent data in the pharmacological treatment of spinal cord injury pain using animal models, and discusses possible clinical applications.

Analgesics↗

PubMed2003

Nanoparticles of polystyrene latexes by semicontinuous microemulsion polymerization using mixed surfactants.

Nanosized polystyrene (PS) latexes stabilized by the mixture of cationic/cationic, anionic/anionic, or anionic/cationic surfactants of various types with high weight ratios of PS to surfactant (ca. 10:1) have been successfully synthesized by a semicontinuous microemulsion polymerization process. For cationic or anionic systems, spherical latex particles with a weight-averaged diameter (Dw) ranging from about 22 to 53 nm were nearly linearly dependent on the weight ratio of the mixed surfactants with similar charges. Their particle size distributions were rather uniform (Dw/Dn < 1.20). For a system with oppositely charged surfactants at nonequimolar ratios, it could produce stable PS particles up to 94 nm in diameter. High molar masses (Mw) of PS ranging from 1.1 to 1.9 x 10(6) g/mol could easily be obtained for all three systems investigated. For both cationic/cationic and anionic/anionic surfactant systems, the number of PS particles per milliliter of latex (Np) generated in the very early stage of O/W' microemulsion remained rather constant throughout the polymerization. This was controlled by using only 1 wt% of mixed surfactants and the continuous addition of a small amount of styrene. The present polymerization method allows one to synthesize nanoparticles of PS or other polymers of high polymer/surfactant weight ratios at some particle sizes that are unable to achieve them with a single type of surfactant.

Emulsions↗

PubMed2002

Buprenorphine alleviates neuropathic pain-like behaviors in rats after spinal cord and peripheral nerve injury.

We have studied and compared the antinociceptive and anti-hyperalgesic effect of the partial opioid receptor agonist buprenorphine in normal and neuropathic rats. In normal rats, systemic buprenorphine produced dose-dependent antinociception on the hot plate test. In rats with peripheral nerve or spinal cord injury, buprenorphine markedly alleviated neuropathic pain-related behaviors, including mechanical and cold allodynia/hyperalgesia at doses comparable to that producing antinociception. The results suggest that buprenorphine may be a useful analgesic for treating neuropathic pain and thus is an atypical opioid since morphine tends to be less potent after nerve injury.

Analgesics, Opioid↗

PubMed2002

Intrathecal [Nphe1]nociceptin( 1-13)NH2 selectively reduces the spinal inhibitory effect of nociceptin.

The effects of intrathecal (i.t.) application of the proposed nociceptin receptor antagonist [Nphe1]nociceptin(1-13)NH2 on the flexor reflex was evaluated in spinalized rats. I.t. [Nphe1]nociceptin (1-13)NH2 dose-dependently facilitated the flexor reflex with no depression. Pretreatment with 16.5 nmol of [Nphe1]nociceptin(1-13)NH2 prevented the development of reflex depression following 0.55 nmol i.t. nociceptin, but strongly enhance the initial excitatory effect of nociceptin. The reflex depressive effect of i.t. endomorphine-2 was not blocked by [Nphe1]nociceptin(1-13)NH2 pretreatment. It is concluded that [Nphe1]nociceptin(1-13)NH2 is a selective antagonist of the spinal receptor mediating the inhibitory action of nociceptin. It can be further suggested that the spinal inhibitory effect of nociceptin may be tonically active.

Analgesics↗

PubMed2002

The role of spinal cholecystokinin in chronic pain states.

It is well established that cholecystokinin (CCK) reduces the antinociceptive effect of opioids. The level of CCK and CCK receptors, as well as CKK release, exhibits considerable plasticity after nerve injury and inflammation, conditions known to be associated with chronic pain. Such altered CCK release coupled in some situation with changes in CCK receptor levels may underlie the clinical phenomenon of varying opioid sensitivity in different clinical pain conditions. In particular, neuropathic pain after injury to the peripheral and central nervous system does not respond well to opioids, which is likely to be caused by increased activity in the endogenous CCK system. CCK receptor antagonists may thus be useful as analgesics in combination with opioids to treat neuropathic pain.

Analgesia↗

PubMed2000

Increased spinal cholecystokinin activity after systemic resiniferatoxin: electrophysiological and in situ hybridization studies.

The present study assessed the effect of a single subcutaneous injection of resiniferatoxin (RTX), an ultrapotent capsaicin analogue, on the activity of spinal cholecystokinin (CCK) systems, by using electrophysiological and in situ hybridization techniques. Subcutaneous RTX at 0.3 mg/kg, but not vehicle, produced marked thermal hypoalgesia in rats on the hot plate and tail flick tests. Partial recovery from hypoalgesia occurred in some (<50%), but not all, RTX-treated rats after 2 weeks. The flexor reflex in response to activation of high threshold afferents was recorded 15-35 days after RTX- or vehicle-treatment. There was no obvious difference between RTX- and vehicle-treated rats in the baseline flexor reflex. Intravenous morphine at 1 mg/kg caused a depression of the flexor reflex in vehicle- and in RTX-treated rats. The reflex depressive effect of morphine was significantly briefer in RTX-treated, non-recovered rats than vehicle-treated rats. Furthermore, CI-988, a high affinity antagonist of CCKB receptors, caused a minor depression of the reflex in vehicle- and RTX-treated rats that had partially recovered, whereas the reflex depressive effect of CI-988 was significantly enhanced in RTX-treated, non-recovered rats. In situ hybridization showed that RTX treatment caused a marked and significant increase in the number of dorsal root ganglion (DRG) neurone profiles expressing CCKB receptor mRNA, whereas only a small increase was observed for CCKA receptor mRNA expressing neurone profiles. Significantly more DRG neurone profiles expressed CCKB receptor mRNA in RTX-treated, non-recovered rats compared to partially recovered rats. RTX-treatment did not influence the expression of CCK mRNA in DRGs. Since CCK functions as a physiological antagonist of morphine, it is suggested that RTX treatment enhances the activity of spinal CCK systems, leading to the reduced effect of morphine and increased effect of the CCKB receptor antagonist CI-988. This may mainly be due to upregulation of CCKB receptors in DRG neurones.

Animals↗

PubMed1998

Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation.

We examined the effects of intrathecal nociceptin, the endogenous ligand for the orphan opioid receptor-like receptor, on abnormal pain-related behaviors in rats after carrageenan-induced inflammation and photochemically-induced peripheral nerve or spinal cord ischemic injury. Intrathecal nociceptin dose-dependently alleviated mechanical and cold allodynia-like behavior in the two models of neuropathic pain. The heat hyperalgesia associated with peripheral inflammation was also significantly reduced, although the efficacy of the antihyperalgesic effect of nociceptin in the inflammation model was decreased. Intrathecal nociceptin also induced significant antinociception on the tail-flick test in all three groups of rats. However, the antinociceptive effect of nociceptin was significantly reduced in rats with peripheral nerve injury. These results indicated that spinally administered nociceptin has anti-allodynic and anti-hyperalgesic effects in animal models of tonic or chronic pain of different origins. Peripheral inflammation and nerve injury may induce spinal plasticity which leads to altered potency and efficacy of nociceptin.

Analgesics↗

PubMed1993

Genetic factors influence the development of mechanical hypersensitivity, motor deficits and morphological damage after transient spinal cord ischemia in the rat.

Genetic influence on the sensory, motor and histopathological outcome of transient spinal cord ischemia was studied in Sprague-Dawley (SD), spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Ischemia caused minor motor deficits and no identifiable morphological damage in the spinal cord of the majority of SD rats after 1 min laser irradiation. However, severe mechanical hypersensitivity, characterized by an allodynia-like reaction to non-noxious tactile and pressure stimuli, was observed for several days in SD rats after spinal cord ischemia. SH rats exhibited less allodynia than SD rats, but developed profound motor deficits. WKY rats, the normotensive progenitor of SH rats, developed both severe mechanical allodynia and motor impairment after spinal cord ischemia. Histological examination revealed that there was significantly more extensive morphological damage in the epicenter of the irradiated segments of the spinal cord in SH and WKY rats than in SD rats after transient spinal cord ischemia. The results indicated that SH rats are more resistant to the development of central pain after central nervous system ischemia, but SH and WKY rats are more susceptible to neuronal damage than SD rats. Thus, genetic variability can lead to variable predisposition for the development of pain and spinal cord damage after ischemia. Such factors may underlie the wide variability in the occurrence of pain after central nervous system injury in humans.

Animals↗

PubMed1992

The depressive effect of intrathecal clonidine on the spinal flexor reflex is enhanced after sciatic nerve section in rats.

The effect of intrathecal (i.t.) alpha 2-adrenoceptor agonist, clonidine, on the spinal nociceptive flexor reflex was studied in decerebrate, spinalized, unanesthetized rats with intact sciatic nerves or in rats in which the sciatic nerve had been ipsilaterally sectioned. In rats with intact nerves i.t. clonidine caused a dose-dependent biphasic effect on flexor reflex excitability. At low dose (10 ng) the effect of clonidine was purely facilitatory, whereas with 50-100 ng clonidine the initial facilitation was often followed by reflex depression. Long-lasting, strong reflex depression was observed after i.t. injection of high doses of clonidine (1 and 10 micrograms). Four to 18 days after sciatic nerve section, the depressive effect of clonidine on the flexor reflex was dramatically enhanced. Depression was frequently observed already with doses of 5 and 10 ng, and maximal depression was reached at 100 ng and 1 micrograms in axotomized rats. The facilitatory effect of low doses of clonidine on the reflex was also observed, although somewhat less frequently than in normals. The depressive effect of clonidine on the flexor reflex was reversed by the selective alpha 2-receptor antagonist, atipamezole (20 micrograms, i.t.), in rats with both intact and sectioned sciatic nerves. The present results revealed an increased sensitivity and effectiveness of the depression of spinal reflex mechanisms by i.t. clonidine after sciatic nerve section, which is opposite to the decreased sensitivity to i.t. morphine after axotomy that we observed previously.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

PubMedDate not supplied

Galanin overexpressing transgenic mice.

Galanin overexpressing transgenic mice (GAL-tg) were generated on two different promoters. Both lines of GAL-tg displayed high levels of galanin in the hippocampus and reduced sensitivity to seizures, as compared to their respective wildtype littermate controls (WT). Performance deficits on learning and memory tasks, impaired long-term potentiation, reduced hippocampal excitability, lower evoked glutamate release, and reduced numbers of choline acetyltransferase immunoreactive neurons in the horizontal limb of the diagonal band were detected in GAL-tg as compared to WT. Changes in sensitivity to nociceptive stimuli were demonstrated in one line. GAL-tg represent a new model for investigating the biological actions of endogenous galanin, and for testing novel therapeutics based on galanin receptor ligands.

Analgesia↗

PubMedDate not supplied

An alternative lidocaine hydrochloride liposomal gel formulation: preparation, percutaneous permeation, and release kinetics.

Liposomal hydrogel formulations of lidocaine hydrochloride (LDH), suitable for topical application, were prepared, and drug percutaneous permeation and release properties were evaluated in vitro. Liposomes composed of lechitin and cholesterol, with LDH entrapped in the inner water compartment, were prepared by the reverse-phase evaporation technique. An optimal hydrogel formulation with carbopol as base included permeation enhancers polyethylene glycol (PEG-400), Azone, poloxamer, and propylene glycol, and this was screened in vitro. Percutaneous permeation kinetic models of LDH in three formulations, liposome solution, conventional gel, and liposomal gel, were studied. Results showed that the mean diameter of LDH liposomes was 88.31+/-6.82 nm and entrapment efficiency was 66.21+/-4.8%. The percutaneous permeation rate of LDH across skin from gel increased after LDH was entrapped in the water compartment of liposome compared with conventional gel, and the permeation kinetics of LDH across skin was not linear, but followed the Higuchi function.

Administration, Topical↗