Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model

Millecamps, Magali; Czerminski, Jan T.; Mathieu, Axel; Stone, Laura S.

doi:10.1016/j.spinee.2015.08.055

Cited by 57 publications

(77 citation statements)

References 51 publications

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“…In mouse models of low back pain associated with intervertebral disc degeneration, we have shown that mice display axial discomfort, characterized by a decreased grip strength similar to that observed in the OVX mice in the current study [15, 22, 47]. Therefore, the decreased grip strength observed here could be a behavioral sign of low back pain.…”

Section: Discussionsupporting

confidence: 81%

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

Suzuki

Millecamps

Naso

et al. 2017

Journal of Osteoporosis

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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.

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Section: Discussionsupporting

confidence: 81%

“…This assay is used to evaluate deep musculoskeletal pain [20] in murine models of bone cancer pain [21], low back pain [22] and muscle inflammation [23]. In this study, grip strength was significantly reduced in OVX, compared to sham-operated, mice 8 weeks after surgery, and persisted for at least 6 months after surgery (Figure 2(e)).…”

Section: Resultsmentioning

confidence: 78%

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

Suzuki

Millecamps

Naso

et al. 2017

Journal of Osteoporosis

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“…Moreover, axial pain was not explicitly evaluated here and would provide additional context to this work, with assays of function also providing meaningful translation to the human low back pain condition. 50 Sustained lumbar spinal glial activation is only evident following the 8 Hz WBV which induces sustained pain ( Figs. 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…Since, hot and/or cold sensitivity have been linked with immune activation in the spinal cord and spinal hyperexciteability, it would be important to also determine if WBV induces similar patterns of thermal sensitivity and if they exhibit any regional differences. Moreover, axial pain was not explicitly evaluated here and would provide additional context to this work, with assays of function also providing meaningful translation to the human low back pain condition …”

Section: Discussionmentioning

confidence: 99%

Whole‐body vibration induces pain and lumbar spinal inflammation responses in the rat that vary with the vibration profile

Zeeman

Kartha

Winkelstein

2016

Journal Orthopaedic Research

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Whole-body vibration (WBV) is linked epidemiologically to neck and back pain in humans, and to forepaw mechanical allodynia and cervical neuroinflammation in a rodent model of WBV, but the response of the low back and lumbar spine to WBV is unknown. A rat model of WBV was used to determine the effect of different WBV exposures on hind paw behavioral sensitivity and neuroinflammation in the lumbar spinal cord. Rats were exposed to 30 min of WBV at either 8 or 15 Hz on days 0 and 7, with the lumbar spinal cord assayed using immunohistochemistry at day 14. Behavioral sensitivity was measured using mechanical stimulation of the hind paws to determine the onset, persistence, and/or recovery of allodynia. Both WBV exposures induce mechanical allodynia 1 day following WBV, but only the 8 Hz WBV induces a sustained decrease in the withdrawal threshold through day 14. Similarly, increased activation of microglia, macrophages, and astrocytes in the superficial dorsal horn of the lumbar spinal cord is only evident after the painful 8 Hz WBV. Moreover, extracellular signal-regulated kinase (ERK)-phosphorylation is most robust in neurons and astrocytes of the dorsal horn, with the most ERK phosphorylation occurring in the 8 Hz group. These findings indicate that a WBV exposure that induces persistent pain also induces a host of neuroimmune cellular activation responses that are also sustained. This work indicates there is an injury-dependent response that is based on the vibration parameters, providing a potentially useful platform for studying mechanisms of painful spinal injuries. ß

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“…Novel treatments are being pursued worldwide to target potential pain generating sources in hopes to treat such pain and improve patient outcomes and quality of life. Animal models of pain have been and are currently being developed to address the pathogenesis of pain, understand pain pathways and mechanisms, and facilitate therapeutic drug discovery and testing [21, 22]. The role of abnormal biomechanics, occupational, lifestyle and psychosocial exposures have been and continue to be addressed to enhance understanding of the causes and consequences of low back pain [11, 12, 17, 18, 23–30].…”

mentioning

confidence: 99%

Thematic series – Low back pain

Samartzis

Grivas

2017

Scoliosis

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Behavioral signs of axial low back pain and motor impairment correlate with the severity of intervertebral disc degeneration in a mouse model

Cited by 57 publications

References 51 publications

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

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

Whole‐body vibration induces pain and lumbar spinal inflammation responses in the rat that vary with the vibration profile

Thematic series – Low back pain

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