title: Chronic Osteoporotic Pain in Mice: Cutaneous and Deep Musculoskeletal Pain Are Partially Independent of Bone Resorption and Differentially Sensitive to Pharmacological Interventions.
abstract: 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.
authors.affiliation: Center for Preventive Medical Sciences, Chiba University, Chiba, Japan.
authors.forename: Miyako
authors.identifier: 0000-0001-6427-3807
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Suite 500, Montreal, QC, Canada H3A 1G1; The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Suite 3200, Montreal, QC, Canada H3G 0G1.
authors.forename: Magali
authors.initials: M
authors.lastname: Millecamps
authors.affiliation: Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Suite 500, Montreal, QC, Canada H3A 1G1; The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Suite 3200, Montreal, QC, Canada H3G 0G1.
authors.forename: Lina
authors.initials: L
authors.lastname: Naso
authors.affiliation: Department of Orthopedic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Seiji
authors.identifier: 0000-0001-5738-6184
authors.initials: S
authors.lastname: Ohtori
authors.affiliation: Center for Preventive Medical Sciences, Chiba University, Chiba, Japan; Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Mori
authors.affiliation: Faculty of Dentistry, McGill University, 2001 McGill College Avenue, Suite 500, Montreal, QC, Canada H3A 1G1; The Alan Edwards Centre for Research on Pain, McGill University, 740 Dr. Penfield Avenue, Suite 3200, Montreal, QC, Canada H3G 0G1.
authors.forename: Laura S
authors.identifier: 0000-0002-7015-2101
authors.initials: LS
authors.lastname: Stone