Pain Hypervigilance is Associated with Greater Clinical Pain Severity and Enhanced Experimental Pain Sensitivity Among Adults with Symptomatic Knee Osteoarthritis

Background

Pain hypervigilance is an important aspect of the fear-avoidance model of pain that may help explain individual differences in pain sensitivity among persons with knee osteoarthritis (OA).

Purpose

The purpose of this study was to examine the contribution of pain hypervigilance to clinical pain severity and experimental pain sensitivity in persons with symptomatic knee OA.

Methods

We analyzed cross-sectional data from 168 adults with symptomatic knee OA. Quantitative sensory testing was used to measure sensitivity to heat pain, pressure pain, and cold pain, as well as temporal summation of heat pain, a marker of central sensitization.

Results

Pain hypervigilance was associated with greater clinical pain severity, as well as greater pressure pain. Pain hypervigilance was also a significant predictor of temporal summation of heat pain.

Conclusions

Pain hypervigilance may be an important contributor to pain reports and experimental pain sensitivity among persons with knee OA.     

Platelet-derived growth factor in vivo: levels, activity, and rate of clearance

Platelet-derived growth factor (PDGF) is a potent mitogen for many cultured connective tissue cells. It is present in concentrated form within the platelet alpha-granules and is believed to be released during platelet degranulation at sites of vascular injury. We have used a sensitive radioreceptor assay to measure PDGF levels in whole blood serum from normal humans [17.5 +/- 3.1 (SD) ng/mL] and baboons (2.7 +/- 1.2 ng/mL). PDGF was not detected in plasma from either species. In addition, plasma was found to substantially reduce the ability of added purified PDGF to bind to the cell surface PDGF receptor on cultured cells, suggesting that plasma may contain a PDGF-binding protein that would serve to inactivate PDGF released into plasma. Calculations of PDGF concentrations in serum have been corrected for the effects of the binding protein. 125I-PDGF injected intravenously into normal baboons was cleared rapidly from the plasma (t1/2 = two minutes). The rapid clearance of 125I-PDGF did not result from iodination damage, as purified unlabeled PDGF was cleared with comparable kinetics. The rapid clearance of purified and iodinated PDGF did not result from changes in PDGF structure during purification or from removal of PDGF-associated proteins during purification, as PDGF present in freeze-thaw lysates of fresh platelets was cleared equally rapidly. We conclude that release of PDGF at sites of vascular injury would greatly increase the local concentration of PDGF and that PDGF not localized to the site of injury would be rapidly cleared from the circulation.     

Site-directed mutagenesis of histidine residues involved in Cu(II) binding and reduction by sperm whale myoglobin.

Sperm whale myoglobin (Mb) reduces Cu(II) through a site-specific mechanism involving complexation by one or more surface histidine residues. Three mutants of Mb, derived from recombinant wild-type Mb, were designed in which surface histidine residues exhibiting strong Cu(II) binding were replaced with amino acids with comparatively poor metal binding characteristics. The kinetics of Cu(II)(Gly)2 reduction by native Mb, recombinant wild-type Mb, and the mutants were compared. Recombinant wild-type Mb reduced Cu(II) at a rate similar to that of native Mb. Two single mutations (His-48----Ala and His-116----Asp) decreased the rate by 31% and 7%, respectively, relative to wild-type Mb and decreased the rate by 38% and 16%, respectively, relative to native Mb. A double mutation (His-113----Ala, His-116----Asp) decreased the rate only slightly more than the single mutation at His-116. Previous NMR studies showed that His-113 exhibits the strongest Cu(II) binding of all surface histidines, but the present experiments suggest that it plays little or no role in the reduction of Cu(II) by Mb. His-48, located 12.7 A from the Fe(II)-heme, participates in one-third of the redox activity of the protein. His-116 appears to play a minor role in the overall redox activity of Mb, but its involvement shows that Mb has the ability to reduce Cu(II) through a histidine residue located more than 20 A from the Fe(II)-heme. These experiments demonstrate that electron transport from the Fe(II)-heme to site-specifically bound Cu(II) can be mediated through multiple pathways in sperm whale Mb.     

Micronuclei of Tetrahymena contain two types of histone H3.

Evidence is presented that micronuclei of Tetrahymena thermophila contain significant amounts of two types of histone H3. One is indistinguishable from that found in macronuclei and the other is unique to micronuclei. The micronucleus-specific H3 has a slightly faster mobility than the common H3 in three different gel systems (both of these species were artifactually lost during procedures for histone preparation in previous studies). Both micronuclear H3s appear to contain a single cysteine residue and are present in sucrose gradient-purified nucleosomes. Acid extracts from micronuclei also contain three prominent high molecular weight proteins that also were lost during previous procedures. These proteins are present in extracts from oligomers but are not observed in extracts from mononucleosomes, suggesting that they may be associated with linker regions between nucleosomes.     

Microcell-mediated transfer of a single human chromosome complements xeroderma pigmentosum group A fibroblasts.

Chromosomes from an immortalized aneuploid human fibroblast cell line were randomly tagged with the selectable marker neo by transfection with the plasmid pSV2neo. Somatic cell fusions between transfected human cells and mouse A9 cells generated pools of G418-resistant human-mouse hybrid clones containing various numbers of human chromosomes. Microcell-mediated chromosome transfer from the hybrid pools to xeroderma pigmentosum complementation group A (XP-A) cells in culture and selection for G418-resistant colonies resulted in the identification of XP cells with enhanced resistance to ultraviolet radiation. Screening of subclones from selected pools of human-mouse hybrids facilitated the identification of hybrids containing a single neo-tagged human chromosome. Transfer of this chromosome to XP-A cells (but not to XP-F or XP-C cells) results in enhanced resistance to ultraviolet light and enhanced excision repair capacity. The identification of a single human chromosome that complements the phenotype of XP-A cells in culture provides the potential for genetic mapping of the complementing gene and for its isolation by molecular cloning.     

A meta analysis of current status of alcohol septal ablation and surgical myectomy for obstructive hypertrophic cardiomyopathy

• Vascular dysfunction at the level of the brachial artery after transradial cardiac catheterization appears transient and resolves within a week
• Chemo‐toxicity from procedural cocktails in addition to catheter‐mediated barotrauma directly to the brachial artery or indirectly from radial trauma may play a role in its etiology.
• Further work is needed to better define the causes of vascular damage from the transradial procedures to develop safer techniques for the future.

     

EXOGEN Ultrasound Bone Healing System for Long Bone Fractures with Non-Union or Delayed Healing: A NICE Medical Technology Guidance

A routine part of the process for developing National Institute for Health and Care Excellence (NICE) medical technologies guidance is a submission of clinical and economic evidence by the technology manufacturer. The Birmingham and Brunel Consortium External Assessment Centre (EAC; a consortium of the University of Birmingham and Brunel University) independently appraised the submission on the EXOGEN bone healing system for long bone fractures with non-union or delayed healing. This article is an overview of the original evidence submitted, the EAC’s findings, and the final NICE guidance issued.