Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions

Although the pathological changes in osteoporotic bones are well established, the characterization of the osteoporotic pain and its appropriate treatment are not fully elucidated. We investigated the behavioral signs of cutaneous and deep musculoskeletal pain and physical function; time-dependent changes in bone mineral density (BMD) and the emergence of the behavioral phenotype; and the effects of pharmacological interventions having different mechanisms of action (chronic intraperitoneal administration of pamidronate [0.25 mg/kg, 5x/week for 5 weeks] versus acute treatment with intraperitoneal morphine [10 mg/kg] and pregabalin [100 mg/kg]) in a mouse model of ovariectomized or sham-operated mice 6 months following surgery. We observed reduced BMD associated with weight gain, referred cutaneous hypersensitivity, and deep musculoskeletal pain that persisted for 6 months. Chronic bisphosphonate treatment, 6 months after ovariectomy, reversed bone loss and hypersensitivity to cold, but other behavioral indices of osteoporotic pain were unchanged. While the efficacy of acute morphine on cutaneous pain was weak, pregabalin was highly effective; deep musculoskeletal pain was intractable. In conclusion, the reversal of bone loss alone is insufficient to manage pain in chronic osteoporosis. Additional treatments, both pharmacological and nonpharmacological, should be implemented to improve quality of life for osteoporosis patients

Therapeutic benefits of the methyl donor S-adenosylmethionine (SAM) on nerve injuryinduced mechanical hypersensitivity and cognitive impairment in mice

Despite considerable advances in understanding mechanisms involved in chronic pain,effective treatment remains elusive. Co-morbid conditions including anxiety, depressionand cognitive impairment further impact quality of life. Chronic pain is associated withreversible changes in brain anatomy and function and with long-term changes in geneexpression. Epigenetic mechanisms, including DNA methylation, contribute to widespreadand long-lasting reprogramming of gene expression. We previously reporteddecreases in global DNA methylation in the mouse frontal cortex six months followinginduction of neuropathic pain using the Spared Nerve Injury (SNI) model. Here weexamined the therapeutic effect of increasing DNA methylation using the methyl donorS-adenosylmethionine (SAM). SAM is marketed as a nutritional supplement for a rangeof conditions including liver disease, depression, osteoarthritis, fibromyalgia anddementia. Three months following SNI or Sham surgery, animals were treated with SAM(20 mg/kg, 3x/week) or saline orally for four months and the impact on sensory, motor,motivational and cognitive indices was measured. [...

Recombinant human erythropoietin in very elderly patients with myelodysplastic syndromes: results from a retrospective study

Myelodysplastic syndromes (MDS) are common in elderly patients. Recombinant human erythro-poietin (rHuEPO) has been widely used to treat anemia in lower risk MDS patients, but few data are known about rHuEPO treatment in the very elderly patient group. In order to investigate the role of rHuEPO treatment in terms of response, overall survival (OS), and toxicity in a very elderly MDS patient group, 93 MDS patients treated with rHuEPO when aged 6580\ua0years were selected among MDS cases enrolled in a retrospective multicenter study by the cooperative group Gruppo Romano Mielodisplasie (GROM) from Jan 2002 to Dec 2010. At baseline, median age was 82.7 (range 80-99.1) with a median hemoglobin (Hb) level of 9\ua0g/dl (range 6-10.8). The initial dose of rHuEPO was standard (epoetin alpha 40,000\ua0IU/week or epoetin beta 30,000\ua0IU/week) in 59 (63.4\ua0%) pa-tients or high in 34 (36.6\ua0%) (epoetin alpha 80,000\ua0IU/week) patients. We observed an erythroid response (ER) in 59 (63.4\ua0%) patients. No thrombotic event was reported. Independent predictive factors for ER were low transfusion requirement before treatment (p\u2009=\u20090.004), ferritin 8\ua0g/dl (p\u2009=\u20090.034), and a high-dose rHuEPO treatment (p\u2009=\u20090.032). Median OS from rHuEPO start was 49.3\ua0months (95\ua0% CI 27.5-68.4) in responders versus 30.6\ua0months (95\ua0% CI 7.3-53.8) in resistant patients (p\u2009=\u20090.185). In conclusion, rHuEPO treatment is safe and effective also in the very elderly MDS patients. However, further larger studies are warranted to evaluate if EPO treatment could be worthwhile in terms of quality of life and cost-efficacy in very old patients