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Biomedical subjects

Ke Ren

Publications and source records attributed to Ke Ren.

52 records · Page 3Linked to original sources
PubMed2003

Swan-shaped bone fixation device made of Ni-Ti shape memory alloy for treating humeral fracture in rabbits.

OBJECTIVE: To establish the animal model for treating humeral fracture with swan-shaped bone fixation device made of Ni-Ti shape memory alloy. METHODS: Models of humeral fractures was established in 30 rabbits and on one side the fracture was fixed with the Ni-Ti shape memory alloy device (SMC side) and on the other with 4-hole dynamic compression plate (DCP side). Anteroposterior radiograph of both humeri were taken at the time points of 2, 4, 8, and 12 weeks respectively after operation. RESULTS: All the rabbits survived the experiment and their forelimbs bore obviously less weight than hindlimb. In SMC side, the humeral fracture healed without either osteoporosis or external callus. The fracture healing in DCP side gave rise to obvious external callus formation, and the healing process took significantly longer time than in SMC group. CONCLUSION: The humerus of rabbit is similar to human humerus in view of their anatomic morphology and biomechanical properties, therefore rabbit humeral fracture models can be ideal for exploring the mechanism of fracture healing induced by the alloy device.

Animals↗
PubMed2002

Activation of spinal kainate receptors after inflammation: behavioral hyperalgesia and subunit gene expression.

We determined whether neural responses to inflammation and hyperalgesia involve activation of kainate receptors, a subgroup of glutamate receptors. Inflammation was introduced into the hind paw by intraplantar injection of complete Freund's adjuvant. The inflammation-induced thermal hyperalgesia was attenuated by intrathecal administration of a non-selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor antagonist, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium (NBQX), as well as by selective kainate receptor antagonists, 6,7,8,9-tetrohydro-5-nitro-1H-benz[g]indole-2,3-dione 3-oxime (NS-102) and 3S,4aR,6S,8aR-6-(4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-deca-hydroisoquinoline-3-carboxylic acid (LY382884). Reverse transcription-polymerase chain reaction (RT-PCR) indicated that the GluR5 and GluR6, but not the GluR7, KA1 and KA2 subunits, exhibited increased mRNA expression at 2 h to 3 days following inflammation (P<0.05). Western blot showed an increase in GluR6 protein levels (P<0.01) with a time course consistent with the changes in its mRNA levels. cDNA sequence and BbvI endonuclease digestion of the GluR6 PCR product revealed that the upregulated GluR6 mRNAs were predominantly the unedited form (Q). These results suggest that a selective upregulation of kainate receptor subunit expression contributes to inflammatory hyperalgesia.

Amino Acid Sequence↗
PubMed2002

Proton transfer within the active-site cavity of carbonic anhydrase III.

The maximal turnover rate of CO2 hydration catalyzed by the carbonic anhydrases is limited by proton transfer steps from the zinc-bound water to solution, steps that regenerate the catalytically active zinc-bound hydroxide. Catalysis of CO2 hydration by wild-type human carbonic anhydrase III (HCA III) (k(cat) = 2 ms (-1)) is the least efficient among the carbonic anhydrases in its class, in part because it lacks an efficient proton shuttle residue. We have used site-directed mutagenesis to test positions within the active-site cavity of HCA III for their ability to carry out proton transfer by replacing various residues with histidine. Catalysis by wild-type HCA III and these six variants was determined from the initial velocity of hydration of CO2 measured by stopped-flow spectrophotometry and from the exchange of 18O between CO2 and H2O at chemical equilibrium by mass spectrometry. The results show that histidine at three positions (Lys64His, Arg67His and Phe131His) have the capacity to transfer protons during catalysis, enhancing maximal velocity of CO2 hydration and 18O exchange from 4- to 15-fold compared with wild-type HCA III. Histidine residues at the other three positions (Trp5His, Tyr7His, Phe20His) showed no firm evidence for proton transfer. These results are discussed in terms of the stereochemistry of the active-site cavity and possible proton transfer pathways.

Binding Sites↗
PubMed2002

Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord during the development and maintenance of inflammatory hyperalgesia.

The present study examined the levels of NMDA receptor NR2 subunit tyrosine phosphorylation in a rat model of inflammation and correlated it with the development of inflammation and hyperalgesia. Hindpaw inflammation and hyperalgesia were induced by intraplantar injection of complete Freund's adjuvant. Proteins from the spinal cord (L4-L5) were immunoprecipitated with anti-NR2A or anti-NR2B antibodies and used for subsequent analysis using 4G-10, a specific anti-phosphotyrosine antibody. Compared with naive rats, there was a rapid and prolonged increase in tyrosine phosphorylation of the NR2B, but not NR2A, subunit after inflammation. The increase in NR2B tyrosine phosphorylation was dependent on primary afferent drive because (1) the phosphorylation correlated with the temporal profile of inflammation and hyperalgesia, (2) shorter-duration noxious stimulation produced a rapid and shorter-lasting increase in phosphorylation, and (3) local anesthetic block of the injected paw reversibly blocked inflammation-induced NR2B tyrosine phosphorylation and delayed hyperalgesia. The increase in NR2B tyrosine phosphorylation was abolished by intrathecal pretreatment with genistein, a tyrosine kinase inhibitor; PP2, an Src family tyrosine kinase inhibitor; AIDA, a group I metabotropic glutamate receptor antagonist; L733,060, an NK1 tachykinin receptor antagonist, and chelerythrine, a protein kinase C inhibitor. In addition, intrathecal PP2 delayed the onset of mechanical hyperalgesia and allodynia. These findings correlate in vivo NMDA receptor tyrosine phosphorylation with the development and maintenance of inflammatory hyperalgesia and suggest that signal transduction upstream to NR2B tyrosine phosphorylation involves G-protein-coupled receptors and PKC and Src family protein tyrosine kinases.

Afferent Pathways↗
PubMed2002

Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models.

Treatment of pain in newborns is associated with problematic drug side effects. Previous studies demonstrate that an intraoral infusion of sucrose and other sweet components of mother's milk are effective in alleviating pain in infant rats and humans. These findings are of considerable significance, as sweet tastants are used in pain and stress management in a number of clinical procedures performed in human infants. The ability of sweet stimuli to induce analgesia is absent in adult rats, suggesting that this is a developmentally transient phenomenon. However, the age range over which intraoral sucrose is capable of producing analgesia is not known. We investigated the effects of intraoral sucrose (7.5%) on nocifensive withdrawal responses to thermal and mechanical stimuli in naive and inflamed rats at postnatal days (P) P0-21. In some rats, Complete Freund's adjuvant (CFA) was injected in a fore- or hindpaw to produce inflammation. In non-inflamed animals, for noxious thermal stimuli, sucrose-induced analgesia emerged at P3, peaked at P7-10, then progressively declined and was absent at P17. For mechanical forepaw stimuli, sucrose-induced analgesia emerged, and was maximal at approximately P10, then declined and was absent at P17. By contrast, maximal sucrose-induced analgesia for mechanical hindpaw stimuli was delayed (P13) compared to that for the forepaw, although it was also absent at P17. In inflamed animals, sucrose reduced hyperesthesia and hyperalgesia assessed with mechanical stimuli. Sucrose-induced analgesia in inflamed animals was initially present at P3 for the forepaw and P13 for the hindpaw, and was absent by P17 for both limbs. Intraoral sucrose produced significantly greater effects on responses in fore- and hindpaws in inflamed rats than in naive rats indicating that it reduces hyperalgesia and allodynia beyond its effects on responses in naive animals. These findings support the hypothesis that sucrose has a selective influence on analgesic mechanisms and that an enhanced sucrose effect takes place in hyperalgesic, inflamed animals as compared to naive animals. Taken together, these results indicate that intraoral sucrose alleviates transient pain in response to thermal and mechanical stimuli, and also effectively reduces inflammatory hyperalgesia and allodynia. Sucrose-induced analgesia is age-dependent and limited to the pre-weaning period in rats. The age-dependency of sucrose-induced analgesia and its differential maturation for the fore- and hindpaw may be due to developmental changes in endogenous analgesic mechanisms and developmental modulation of the interaction between gustatory and pain modulatory pathways.

Acute Disease↗
PubMed2002

Plasticity in excitatory amino acid receptor-mediated descending pain modulation after inflammation.

The role for excitatory amino acids (EAAs) in the rostral ventromedial medulla (RVM) in descending pain modulation after persistent noxious input is unclear. In an animal model of inflammatory hyperalgesia, we examined the effects of intra-RVM microinjection of EAA receptor agonists and antagonists on paw withdrawal and tail-flick responses in lightly anesthetized rats. N-Methyl-D-aspartate (NMDA) produced effects that depended upon the postinflammatory time period. At 3 h postinflammation, NMDA induced facilitation at a lower dose (10 pmol) and inhibition at a higher dose (1000 pmol). At 24 h postinflammation, NMDA (0.1-1000 pmol) produced a dose-dependent inhibition. The facilitation and inhibition, respectively, were attenuated significantly by the preadministration of an NMDA receptor antagonist, DL-2-amino-5-phosphonovaleric acid (APV) (10 pmol, P < 0.05), to the same site. Intra-RVM microinjection of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) (0.1-100 pmol) produced dose-dependent inhibition at both 3 and 24 h postinflammation that was blocked by the preadministration of an AMPA/kainate receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (100 pmol, P < 0.05). Unexpectedly, AMPA-produced inhibition was also significantly attenuated by preadministration of APV (10 pmol, P < 0.05). Compared with 3 h postinflammation, both NMDA and AMPA showed a leftward shift in their dose-response curves at 24 h postinflammation. These results demonstrate that NMDA and AMPA receptors in the RVM are involved in the descending modulation after inflammatory hyperalgesia. There is a time-dependent increase in EAA neurotransmission in the RVM after inflammation and NMDA receptors play an important role in AMPA-produced inhibition.

Animals↗
PubMed1999

Endogenous mechanisms of sensory modulation.

We provide evidence supporting the idea that the relationship between tissue damage, or the threat of tissue damage, and the response to such stimuli is variant and dependent on neuronal networks by which attentional, emotional and cognitive components of pain experience activate endogenous descending modulatory systems. Most previous studies have focused on responses to transient noxious stimuli with little information on the influence of descending modulation on behavioral responses to persistent pain and hyperalgesia after tissue or nerve injury. Utilizing correlative behavioral and neuronal studies we have demonstrated that (1) behavioral context modulates neuronal activity in nociceptive and non-nociceptive somatosensory pathways, supporting the hypothesis that responses in these pathways are not immutable; (2) descending modulation influences behavior and neuronal activity at spinal cord levels after inflammation and persistent pain; and (3) there are descending facilitatory as well as inhibitory influences on behavior and spinal cord neuronal activity that may impact on persistent pain particularly of deep muscle and visceral origin. Cortical as well as subcortical pathways are available by which dorsal horn activity can be modulated by attentional, motivational and cognitive factors. It appears that the same neuronal mechanisms in the forebrain and brain stem are available for behavioral modulation in a learned task involving the threat of tissue damage (transient noxious stimuli) as are available in the development and amplification of persistent pain produced by inflammation. These parallel brain mechanisms emphasize the saliency of pain experience as an important learned behavior for the survival of the organism, similar to sequential goal-directed behaviors in an operant task.

Animals↗
PubMed1999

Inflammatory Models of Pain and Hyperalgesia.

This article addresses important pain research models in nonhuman animals. These models attempt to mimic human persistent pain conditions. Models of persistent pain employ inflammatory agents that produce discomfort and hyperalgesia (i.e., an enhanced response to a noxious stimulus). The models are associated with skin, subcutaneous tissue, and joint inflammation (somatic structures). Studies employing such models have led to significantly improved understanding of mechanisms of somatic pain. It is important that investigators assess the level of pain produced in these animals and provide analgesic agents whenever it does not interfere with the purpose of the experiment. Pain can be inferred from ongoing behavioral variables such as feeding and drinking, sleep-waking cycle, grooming, and social behavior.

Journal Article↗
PubMed1994

Inflammation and hyperalgesia in rats neonatally treated with capsaicin: effects on two classes of nociceptive neurons in the superficial dorsal horn.

To address the mechanisms of hyperalgesia and dorsal horn plasticity following peripheral tissue inflammation, the effects of adjuvant-induced inflammation of the rat hindpaw on behavioral nociception and nociceptive neuronal activity in the superficial dorsal horn were examined in neonatally capsaicin-treated rats 6-8 weeks of age. Capsaicin treatment resulted in an 82% loss of unmyelinated fibers in L5 dorsal roots, a dramatic reduction of substance P-like immunoreactivity in the spinal cord, and a significant decrease in the percentage of dorsal horn nociceptive neurons that responded to C-fiber stimulation and noxious heating of the skin. The thermal nociceptive threshold was significantly increased in capsaicin-treated rats, but behavioral hyperalgesia to thermal stimuli still developed in response to inflammation. Following inflammation, there was a significant decrease in mechanical threshold and an increase in response duration to mechanical stimuli in both vehicle- and capsaicin-treated rats, suggesting that a state of mechanical hyperalgesia was also induced. The capsaicin treatment appears to have differential effects on nociceptive specific (NS) and wide-dynamic-range (WDR) neurons in inflamed rats. Expansion of the receptive fields of nociceptive neurons, a measure of the effect of inflammation-induced CNS plasticity, was less extensive for NS than for WDR neurons in capsaicin-treated rats. Compared to vehicle-treated rats, a smaller population of NS neurons, but a similar percentage of WDR neurons, had background activity in inflamed capsaicin-treated rats. C-fiber strength electrical stimulation of the sciatic nerve produced expansion of the receptive fields in a greater portion of NS neurons (53%, P < 0.05) in capsaicin- than in vehicle-treated rats (32%). There was no difference in stimulation-induced expansion of the receptive fields for WDR neurons between vehicle- or capsaicin-treated rats. An N-methyl-D-aspartate receptor antagonist, MK-801, attenuated the behavioral hyperalgesia and reduced the receptive field size of dorsal horn neurons in inflamed capsaicin- and vehicle-treated rats. The data suggest that while capsaicin-sensitive primary afferents may be involved in neuronal plasticity induced by peripheral tissue inflammation, changes in the capsaicin-insensitive WDR and NS populations are sufficient to produce thermal and mechanical hyperalgesia after the loss of capsaicin-sensitive primary afferents.

Animals↗
PubMed1994

Primary sensory neurons exhibit altered gene expression in a rat model of neuropathic pain.

Using a number of complementary anatomical and molecular techniques, we studied the effects of chronic constriction injury (CCI), a model of partial nerve injury that elicits behavioral hyperalgesia, on primary sensory neurons in the rat. Dorsal root ganglia taken from animals with CCI were analyzed for alterations in mRNA levels encoding growth-associated protein-43 (GAP-43), calcitonin gene-related peptide (CGRP), galanin (GAL), neuropeptide Y (NPY), substance P (SP), and vasoactive intestinal polypeptide (VIP). We found that GAP-43 expression increased 3-fold, peaking between 7 and 14 days after development of the CCI. However, within this same 7-14 day time frame, both CGRP and SP mRNAs fell to half their normally abundant constitutive levels of expression. The most dramatic change in expression occurred for GAL, NPY and VIP mRNAs which all rose rapidly (day 3) from non-detectable levels. Similar alterations in gene expression have been described after complete sciatic nerve transection or crush.

Animals↗
PubMed1992

The effects of a non-competitive NMDA receptor antagonist, MK-801, on behavioral hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation.

The involvement of NMDA receptors in rats with peripheral inflammation and hyperalgesia was evaluated by administration of the non-competitive NMDA receptor antagonist, MK-801. Inflammation and hyperalgesia was induced by intradermal injection of complete Freund's adjuvant (CFA) or carrageenan into the left hind paw. The latency of paw withdrawal from a thermal stimulus was used as a measure of hyperalgesia in awake rats. MK-801 (1.6 mg/kg, i.p., or 31.5 micrograms, intrathecal) significantly attenuated thermal hyperalgesia and reduced its duration in comparison to saline-injected rats (P less than 0.05). The receptive field size of nociceptive-specific and wide-dynamic-range neurons in the superficial and deep spinal dorsal horn recorded 24 h after injection of CFA was significantly reduced to 73 +/- 6% (P less than 0.05, n = 8) and 74 +/- 4% (P less than 0.05, n = 8) of control values, respectively, by a cumulative dose of 3 mg/kg of MK-801 (i.v.). MK-801 (2 mg/kg) prevented the expansion of the receptive fields of dorsal horn neurons recorded 5 +/- 0.4 h (n = 5) after intradermal injection of CFA as compared to saline-injected rats (P less than 0.05). MK-801 had no significant effect on receptive field size of dorsal horn neurons in rats without CFA-induced inflammation but blocked a transient expansion of the receptive fields induced by 1 Hz, C-fiber intensity electrical stimulation of the sciatic nerve. The background activity and noxious heat-evoked response of dorsal horn neurons in rats with CFA-induced inflammation were primarily inhibited and noxious pinch-evoked activity was both facilitated and inhibited by the administration of MK-801. These results support the hypothesis that NMDA receptors are involved in the dorsal horn neuronal plasticity and behavioral hyperalgesia that follows peripheral tissue inflammation.

Animals↗
PubMed1991

Spinal serotonergic and kappa opioid receptors mediate facilitation of the tail flick reflex produced by vagal afferent stimulation.

Facilitation of the nociceptive tail flick (TF) reflex produced by low intensity (2.0 msec, 20 Hz) electrical stimulation of cervical vagal afferents (VAS) was studied in rats lightly anesthetized with pentobarbital. Serotonin (methysergide, LY 53857 or ICS 205-930), adrenergic (prazosin or yohimbine) or opioid (naloxone, nor-binaltorphimine or naltrindole) receptor antagonists were administered into the subarachnoid space of the lumbar enlargement to characterize the spinal receptors mediating VAS-produced facilitation. Spinal 5-HT1 and kappa-opioid receptors were determined to be involved in facilitation of the TF reflex produced by VAS, suggesting that facilitation of spinal nociceptive transmission by activation of cervical vagal afferents is mediated by subtypes of spinal serotonergic and opioid receptors.

Animals↗
PubMed1987

WDR response profiles of spinal dorsal horn neurons may be unmasked by barbiturate anesthesia.

The number of WDR (convergent, multireceptive) neurons encountered in the spinal dorsal horn of physiologically intact, awake, drug-free cats has been much smaller than expected (9% in intact, drug-free animals). Control studies in barbiturate-anesthetized or spinal cord transected animals indicate that the dearth of WDR neurons was not just an artifact of the chronic recording technique. In those preparations WDR neurons represented 34% and 61% of the sample, respectively. Initial studies in which the effects of light barbiturate anesthesia on spinal dorsal horn neurons (n = 12) have been examined revealed that a 20 mg/kg dose of pentobarbital can, in some neurons (n = 4), unmask thermally evoked activity that was not present in the intact, drug-free animal. Responses to noxious mechanical stimuli were also enhanced following barbiturate administration. These changes resulted in a reclassification of neural type from low threshold in the intact, awake, drug-free animal to WDR in the anesthetized animal.

Anesthetics↗