Joints Pain
One Symptom Many Causes

Extracellular MicroRNAs Activate Nociceptor Neurons to Elicit Pain via TLR7 and TRPA1, 2014

Highlights

• miRNAs sequence dependently activate nociceptive neurons via TLR7 and TRPA1
• TLR7 is functionally coupled to TRPA1 in primary sensory neurons and HEK293 cells
• miRNA let-7b elicits nocifensive pain via TLR7 and TRPA1 but not TRPV1
• Endogenous let-7b is released by neuronal activation to induce inflammatory pain

Clinical Reports

A woman with rheumatoid arthritis, Sjögren's Syndrome, leg ulcer, and significant weight loss, 2012 Full Text

Modeling joints pain

Prediction model for knee osteoarthritis based on genetic and clinical information. 2010

Abstract
INTRODUCTION:
Osteoarthritis (OA) is the most common bone and joint disease influenced by genetic and environmental factors. Recent association studies have uncovered the genetic factors behind OA, its susceptibility genes, which would enable us to predict disease occurrence based on genotype information. However, most previous studies have evaluated the effects of only a single susceptibility gene, and hence prediction based on such information is not as reliable. Here, we constructed OA-prediction models based on genotype information from a case-control association study and tested their predictability.

METHODS:
We genotyped risk alleles of the three susceptibility genes, asporin (ASPN), growth differentiation factor 5 (GDF5), and double von Willebrand factor A domains (DVWA) for a total of 2,158 Japanese subjects (933 OA and 1,225 controls) and statistically analyzed their effects. After that, we constructed prediction models by using the logistic regression analysis.

RESULTS:
When the effects of each allele were assumed to be the same and multiplicative, each additional risk allele increased the odds ratio (OR) by a factor of 1.23 (95% confidence interval (CI), 1.12 to 1.34). Individuals with five or six risk alleles showed significantly higher susceptibility when compared with those with zero or one, with an OR of 2.67 (95% CI, 1.46 to 4.87; P = 0.0020). Statistical evaluation of the prediction power of models showed that a model using only genotyping data had poor predictability. We obtained a model with good predictability by incorporating clinical data, which was further improved by rigorous age adjustment.

CONCLUSIONS:
Our results showed that consideration of adjusted clinical information, as well as increases in the number of risk alleles to be integrated, is critical for OA prediction by using data from case-control studies. To the authors' knowledge, this is the first report of the OA-prediction model combining both genetic and clinical information.

Dietary supplements

Long-chain polyunsaturated fatty acids and the pathophysiology of myalgic encephalomyelitis (chronic fatigue syndrome). 2007

A potential therapeutic avenue could be offered by bypassing the inhibition of the enzyme delta-6-desaturase by treatment with virgin cold-pressed non-raffinated evening primrose oil, which would supply gamma-linolenic acid and lipophilic pentacyclic triterpenes, and with eicosapentaenoic acid. The gamma-linolenic acid can readily be converted into dihomo-gamma-linolenic acid and thence arachidonic acid, while triterpenes have important free radical scavenging, cyclo-oxygenase and neutrophil elastase inhibitory activities. Furthermore, both arachidonic acid and eicosapentaenoic acid are, at relatively low concentrations, directly virucidal.

Local Therapy

Gestione appropriata del dolore articolare
nell’anziano fragile

Il medico di famiglia è il primo punto di riferimento per il paziente affetto da dolore cronico e questo comporta che egli abbia un ruolo attivo per affrontare in modo appropriato questo rilevante problema clinico. In particolare nei soggetti anziani e fragili il dolore di natura articolare è il più frequente e limita pesantemente la loro autonomia e la qualità della loro vita. In questo setting di pazienti, che necessita di una attenzione particolare, il Mmg è l’attore principale nel fornire consigli terapeutici in base al loro profilo clinico.
Gli antinfiammatori non steroidei sono tra i farmaci più utilizzati per il controllo del dolore muscolo-scheletrico acuto o cronico, tuttavia specialmente nei pazienti anziani è importante tenere conto del loro profilo di tollerabilità e delle loro potenziali reazioni avverse, in particolare a livello dell’apparato cardiovascolare oltre ai noti problemi di intolleranza gastrica che aumentano di prevalenza con l’aumentare dell’età.
Soprattutto nella gestione del dolore articolare alle articolazioni superficiali (caviglie, ginocchia, spalla, gomito, mani) un’attenzione particolare potrebbe essere dedicata agli antinfiammatori non steroidei per uso topico che non presentano rischi per il paziente. In questo scenario ben si inserisce diclofenac 2% gel che garantisce un buon assorbimento per via cutanea con concentrazioni efficaci di farmaco a livello delle articolazioni, in grado di risolvere rapidamente il dolore e ridare una funzionalità alle articolazioni colpite. La somministrazione topica di diclofenac 2%, che ha il vantaggio di evitare l’assorbimento sistemico, permette di evitare problemi di interazioni farmacologiche ed è particolarmente indicata nei pazienti anziani e fragili che spesso presentano comorbidità e sono in politerapia.

Kynurenine pathway metabolism in patients with osteoporosis after 2 years of drug treatment. 2006
Back and neck pain exhibit many common features in old age: a population-based study of 4,486 Danish twins 70-102 years of age. 2004
Study of anemia in long-term care (SALT): prevalence of anemia and its relationship with the risk of falls in nursing home residents. 2008

What is new about crystals other than monosodium urate? 2000

Antibiotici attivi contro l'artrite da Chlamydia
Un trattamento antibiotico della durata di 6 mesi risulta efficace contro l'artrite reattiva indotta da Chlamydia. Lo testimonia uno studio prospettico in doppio cieco placebo-controllato di 9 mesi che ha posto a confronto tre gruppi di pazienti trattati per sei mesi con: doxiciclina e rifampicina più placebo (al posto di azitromicina); azitromicina e rifampicina più placebo (al posto di doxiciclina); solo placebo al posto dei tre antibiotici. Tutti i pazienti arruolati soffrivano di artrite e risultavano positivi a C. trachomatis o C. pneumoniae. L'end-point primario, ovvero il miglioramento del 20% o più in almeno 4 variabili e nessun peggioramento in tutte le variabili rispetto ai valori di partenza, è stato raggiunto, dopo sei mesi di terapia, nel 63% dei pazienti trattati con le combinazioni farmacologiche e solo nel 20% dei soggetti del gruppo placebo. Risultati simili nel gruppo trattato si sono avuti in alcuni endpoint secondari di efficacia, con il miglioramento significativo della conta delle articolazioni tumefatte o dolenti, del giudizio globale medico e un trend positivo della velocità di eritrosedimentazione. Il 22% delle persone in trattamento attivo ha dichiarato di ritenere di aver raggiunto la completa remissione dei sintomi durante il trial, un end-point secondario che non è stato riscontrato in alcun paziente del gruppo placebo. Inoltre, a fronte di una sostanziale sovrapponibilità del rischio di eventi avversi, un numero significativamente maggiore di pazienti nei due gruppi trattati con antibiotici è diventato negativo al test PCR per la Chlamydia al sesto mese.

Combination antibiotics as a treatment for chronic Chlamydia-induced reactive arthritis.Arthr & Rheum 2010; 62: 1298-1307.

PCR analyses. All patients had to be positive for either C trachomatis or C pneumoniae by PCR in PBMCs or synovial tissue in order to be randomized to treatment.
Of the 80 subjects screened, 45 met these criteria.

Figure 1. A, Modified swollen joint counts in patients receiving combination antibiotics compared with those receiving placebo. = P = 0.0001; = P < 0.0001; # = P = 0.0007; ## = P = 0.0005, versus baseline. B, Tender joint counts in patients receiving combination antibiotics compared with those receiving placebo. = P = 0.0009; = P < 0.0001; # = P = 0.002; ## = P = 0.0004, versus baseline. Values are the mean.

Treatment

Those subjects who were positive by PCR for either chlamydial species in PBMCs and/or synovial tissue were randomly assigned (1:1:1) to 1 of 3 treatment groups; randomization was stratified by age (<40 years or 40 years) and disease duration (0.5-2 years or >2 years) in order to achieve a more homogeneous patient population in each of the 3 groups. The first group received 100 mg doxycycline by mouth twice daily and 300 mg rifampin by mouth daily plus placebo instead of azithromycin; the second group received 500 mg azithromycin by mouth daily for 5 days and then 500 mg azithromycin by mouth twice weekly and 300 mg rifampin by mouth daily plus placebo instead of doxycycline; the third group received 3 placebos instead of azithromycin, doxycycline, and rifampin. All 3 groups were treated for a total of 6 months and followed up for 3 months after completion of the study drugs (total of 9 months). The purpose of the month 9 visit was to determine whether the patient's condition had worsened after discontinuing study medications.

In addition to the study drugs, patients were allowed to take oral corticosteroids (10 mg/day prednisone or equivalent) and/or nonsteroidal antiinflammatory drugs (NSAIDs) if they had been receiving stable doses for >4 weeks prior to randomization; DMARDs and biologic agents were allowed if subjects had been receiving stable doses >12 weeks prior to randomization. The doses of these medications could not be increased; however, if the subject experienced clinical improvement during the study, downward adjustment of these background medications was allowed.

Treatment details

All randomized study patients received at least 1 dose of the study drugs and were included in the ITT and safety analyses. Thirty-four of 42 subjects (81%) completed the 6 months of treatment; 3 of 27 subjects (11%) receiving combination antibiotics and 5 of 15 subjects (33%) receiving placebo discontinued the study medications prematurely. Of the 3 subjects receiving combination antibiotics who discontinued prematurely, 2 were receiving doxycycline and rifampin (reasons for discontinuation were peripheral edema and loss to followup), and 1 was receiving azithromycin and rifampin (reason for discontinuation was loss to followup). Regarding the 5 subjects receiving placebo, the reasons for discontinuation were lack of efficacy (n = 1), nausea and diarrhea (n = 1), seizures (n = 1), withdrawal of consent (n = 1), and loss to followup (n = 1).