Acid-induced experimental knee pain and hyperalgesia in healthy humans.

Inflammation and the related acidity in peri-articular structures may be involved in pain generation and hyperalgesia in knee osteoarthritis. This study investigated pain and associated hyperalgesia provoked by infusion of acidic saline into the infrapatellar fat pad. Twenty-eight subjects participated in two sessions in which acidic saline (AS, pH 5) or neutral saline (NS, pH 7.4) were infused into the infrapatellar fat pad for 15 min. Pain intensity, pain area, mechanical and thermal sensitivity, and maximal voluntary knee extension force were recorded. Repeated infusions were performed in 14 subjects. Infusion of AS caused significantly higher pain intensity, larger pain areas, induced hyperalgesia around the infused knee, and reduced extension force. No significant pain facilitation or spreading of hyperalgesia was found after repeated infusions as compared with single infusions. Acidic saline infused into the infrapatellar fat pad provoked pain and localized mechanical hyperalgesia. Thus, this acid-induced pain model may mimic the early-stage responses to tissue injury of knee osteoarthritis.

Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain.

OBJECTIVE: To assess the functional changes of Transient receptor potential vanilloid 1 (TRPV1) receptor and to clarify its mechanism in a rat mono-iodoacetate (MIA)-induced joint pain model (MIA rats), which has joint degeneration with cartilage loss similar to osteoarthritis. METHODS: Sensitization of TRPV1 in MIA rats was assessed by transient spontaneous pain behavior induced by capsaicin injection in knee joints and electrophysiological changes of dorsal root ganglion (DRG) neurons innervating knee joints in response to capsaicin. Mechanisms of TRPV1 sensitization were analyzed by a newly developed sandwich enzyme-linked immunosorbent assay that detects phosphorylated TRPV1, followed by functional and expression analyses of protein kinase C (PKC) in vivo and in vitro, which involves TRPV1 phosphorylation. RESULTS: Pain-related behavior induced by intra-articular injection of capsaicin was significantly increased in MIA rats compared with sham rats. In addition, capsaicin sensitivity, evaluated by capsaicin-induced inward currents, was significantly increased in DRG neurons of MIA rats. Protein levels of TRPV1 remained unchanged, but phosphorylated TRPV1 at Ser800 increased in DRG neurons of MIA rats. Phosphorylated-PKCɛ (p-PKCɛ) increased and co-localized with TRPV1 in DRG neurons of MIA rats. Capsaicin-induced pain-related behavior in MIA rats was inhibited by intra-articular pretreatment of the PKC inhibitor bisindolylmaleimide I. In addition, intra-articular injection of the PKC activator phorbol 12-myristate 13-acetate increased capsaicin-induced pain-related behavior in normal rats. CONCLUSION: TRPV1 was sensitized at the knee joint and at DRG neurons of MIA rats through PKC activation. Thus, TRPV1 sensitization might be involved in chronic pain caused by osteoarthritis.

Effects of duloxetine on pain and walking distance in neuropathic pain models via modulation of the spinal monoamine system.

BACKGROUND: Approximately 40% of patients with chronic low back pain have a neuropathic component. In this study, we assessed the effects of analgesics on tactile hypersensitivity and walking distance in the rat cauda equina compression (CEC) model of neuropathic low back pain. METHODS: The effects of analgesics on tactile hypersensitivity were examined using the von Frey test in CEC and partial sciatic nerve ligation (pSNL) models. Effects on walking distance were assessed using a treadmill test. Levels of α2δ1 subunit and ATF-3 mRNA in dorsal-root ganglion (DRG) neurons and those of α2δ1 subunit protein in the spinal cord were determined using quantitative RT-PCR and western blotting, respectively. Histological features were assessed using immunohistological methods. RESULTS: Histological changes indicating nerve damage (increase in ATF-3 mRNA, decrease in NF-200 and an increase in CD68 immunoreactivity) were observed in the CEC model. Duloxetine had analgesic effects in both models and improved walking distance in the CEC model. Pregabalin had analgesic effects in both models; however, the effect was weaker in the CEC model than in the pSNL model. α2δ1 subunit expression in DRG neurons and in the spinal cord was unchanged in the CEC model, but significantly increased in the pSNL model. Indomethacin had no analgesic effect in either model. Intrathecal yohimbine inhibited the effects of duloxetine with significant effects on depression. CONCLUSIONS: These findings suggest that the analgesic effects of duloxetine are mainly mediated by the spinal monoamine system, independent of the antidepressant effects of this agent. SIGNIFICANCE: The findings of this study suggest that duloxetine may be an effective treatment of broad neuropathic pain states, including neuropathic low back pain. The analgesic effects of duloxetine might be mediated by alterations of the descending pain modulatory pathways in the spinal cord, independent of the antidepressant effects.

Identification of a novel fibroblast growth factor, FGF-22, preferentially expressed in the inner root sheath of the hair follicle.

We isolated cDNA encoding a novel fibroblast growth factor (FGF-22) (170 amino acids) from human placenta. Of the FGF family members, FGF-22, which appears to be a secreted protein, is most similar to FGF-10 and FGF-7 (approximately 46% and approximately 40% amino acid identities, respectively). The human FGF-22 gene was localized on chromosome 19p13.3. We also isolated mouse cDNA encoding FGF-22 (162 amino acids) from the skin. Mouse FGF-22 shows high homology (87% amino acid identity) to human FGF-22. Mouse FGF-22 mRNA was found to be preferentially expressed in the skin among the mouse adult tissues examined by Northern blotting analysis. By in situ hybridization, FGF-22 mRNA in the skin was found to be preferentially expressed in the inner root sheath of the hair follicle. Therefore, FGF-22 is expected to be a unique FGF that plays a role in hair development.

Optical resonant ultrasound spectroscopy for fluid properties measurement.

The properties of fluids are studied using unusually small containment spherical resonators. Proper identification of resonant fluid signatures allows determination of pressure and density of the internal gas with great accuracy using an appropriate equation of state (EOS). Low noise and high sensitivity detection of vibration are critical parameters to characterizing the contained gas when its pressure approaches 1 atm or less. The benefits of using spherical resonators to determine fluid properties are discussed, and some example calculations of sound speed are presented. In addition to measuring fluids, a comparative experimental approach is taken to explore and, eventually, to optimize vibration detection. In the experiments, two detection methods, a contact piezoelectric transducer (PZT) device and a non-contact optical device, are compared simultaneously and quantitatively. This is done in a unique manner without change in vibration coupling to the sample between tests. A commercially available resonant ultrasound spectroscopy system is used as the contact system, while another commercial device (used as the non-contact vibration detector) combined with the same excitation source (used in the contact system) comprises the other system. The non-contact detector is an optical interferometric receiver that provides adaptation to optically rough surfaces and high sensitivity to acoustic displacements through optical interference in photorefractive GaAs. Both vibration detection systems are compared with particular emphasis on displacement sensitivity, frequency response, and noise level. Furthermore, the results from comparing detection modalities are presented, and their effects on fluid properties measurement are discussed.

Interaction of oxygen with TiN(001): N<-->O exchange and oxidation process.

This work presents a detailed experimental and theoretical study of the oxidation of TiN(001) using a combination of synchrotron-based photoemission and density functional theory (DFT). Experimentally, the adsorption of O2 on TiN(001) was investigated at temperatures between 250 and 450 K. At the lowest temperature, there was chemisorption of oxygen (O(2,gas)-->2O(ads)) without significant surface oxidation. In contrast, at 450 K the amount of O2 adsorbed increased continuously, there was no evidence for an oxygen saturation coverage, a clear signal in the Ti 2p core level spectra denoted the presence of TiOx species, and desorption of both N2 and NO was detected. The DFT calculations show that the adsorption/dissociation of O2 is highly exothermic on a TiN(001) substrate and is carried out mainly by the Ti centers. A high oxygen coverage (larger than 0.5 ML) may induce some structural reconstructions of the surface. The exchange of a surface N atom by an O adatom is a highly endothermic process (DeltaE=2.84 eV). However, the overall oxidation of the surface layer is thermodynamically favored due to the energy released by the dissociative adsorption of O2 and the formation of N2 or NO. Both experimental and theoretical results lead to conclude that a TiN+mO2 -->TiOx + NO reaction is an important exit channel for nitrogen in the oxidation process.

Cloning and characterization of a chromosomal gene cluster, pah, that encodes the upper pathway for phenanthrene and naphthalene utilization by Pseudomonas putida OUS82.

A 25-kb DNA SalI fragment cloned from the chromosomal DNA of Pseudomonas putida OUS82, which utilizes phenanthrene (Phn+) and naphthalene (Nah+), carried all of the genes necessary for upper naphthalene catabolism. Cosmid recombinant pIP7 complemented both the Nah- and Phn- defects of OUS8211 (Trp-Nah-Phn-Sal+[salicylate utilizing]Hna+[1-hydroxy-2-naphthoate utilizing]) and only the Phn- defect of OUS8212 (Trp-Nah-Phn-Sal-Hna+). The results indicate that strain OUS82 uses different pathways after o-hydroxycarboxylic aromatics in the catabolism of naphthalene and phenanthrene.