Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I

Sabsovich, Ilya; Wei, Tzuping; Guo, Tian-Zhi; Zhao, Rong; Shi, Xiaoshuang; Li, Xiangqi; Yeomans, David C.; Klyukinov, M.; Kingery, Wade S.; Clark, David J.

doi:10.1016/j.pain.2007.11.004

Cited by 108 publications

(131 citation statements)

References 59 publications

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“…Tibial fracture is an established experimental rodent model to study clinically relevant orthopedic procedures (14) and a variety of clinical pathologies ranging from postoperative pain, complex regional pain syndrome, and POCD to bone cancer (15)(16)(17)(18)(19).…”

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confidence: 99%

“…After fracture, nociceptive sensations have been associated with excessive substance P signaling and exaggerated regional inflammatory responses leading to the increased release of systemic proinflammatory cytokines such as tumor necrosis factor alpha and interleukin 1 beta (18,20,21). Similar changes in proinflammatory cytokines and activation of nuclear factor κB signaling in macrophages have been associated with changes in blood-brain barrier permeability, hippocampal neuroinflammation, and subsequent cognitive impairment in mice after tibial fracture (22)(23)(24).…”

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confidence: 99%

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Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Zhang

Barde

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Pain is a critical component hindering recovery and regaining of function after surgery, particularly in the elderly. Understanding the role of pain signaling after surgery may lead to novel interventions for common complications such as delirium and postoperative cognitive dysfunction. Using a model of tibial fracture with intramedullary pinning in male mice, associated with cognitive deficits, we characterized the effects on the primary somatosensory system. Here we show that tibial fracture with pinning triggers cold allodynia and up-regulates nerve injury and inflammatory markers in dorsal root ganglia (DRGs) and spinal cord up to 2 wk after intervention. At 72 h after surgery, there is an increase in activating transcription factor 3 (ATF3), the neuropeptides galanin and neuropeptide Y (NPY), brain-derived neurotrophic factor (BDNF), as well as neuroinflammatory markers including ionized calcium-binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and the fractalkine receptor CX3CR1 in DRGs. Using an established model of complete transection of the sciatic nerve for comparison, we observed similar but more pronounced changes in these markers. However, protein levels of BDNF remained elevated for a longer period after fracture. In the hippocampus, BDNF protein levels were increased, yet there were no changes in Bdnf mRNA in the parent granule cell bodies. Further, c-Fos was down-regulated in the hippocampus, together with a reduction in neurogenesis in the subgranular zone. Taken together, our results suggest that attenuated BDNF release and signaling in the dentate gyrus may account for cognitive and mental deficits sometimes observed after surgery.postoperative pain | nerve injury | memory | delirium | neurogenesis

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confidence: 99%

mentioning

confidence: 99%

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Zhang

Barde

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…[54][55][56][57] Treating fracture rats with TNF, IL-1, IL-6, or NGF receptor antagonists or inhibitors partially inhibits post-fracture allodynia and unweighting, but unlike alendronate, these treatments were ineffective at preventing trabecular bone loss in the CRPS fracture model. [16][17][18]58 Recently we observed that B cells contributed to the development and maintenance of CRPS -like changes in the mouse fracture model and postulated that IgM autoantibodies directed at antigens in the fracture limb skin and nerves contribute to nociceptive sensitization in CRPS. 23 Clinical support for this hypothesis include a recent study demonstrating that a third of CRPS patients exhibit strongly positive antinuclear antibody tests, a standard diagnostic test for autoimmune disease, 59 and small randomized trial of low dose IVIG demonstrated that some chronic CRPS patients had prolonged and dramatic symptom improvement after a single IVIG treatment 60 .…”

Section: Discussionmentioning

confidence: 99%

“…Fos immunostaining was performed as previously described. 17,18 Because the sciatic nerve projects heavily to the L3-L5 segments of the spinal cord, we analyzed the numbers of Fos immunoreactive (Fos-IR) neurons at those levels.…”

Section: Fos Spinal Cord Immunohistochemistrymentioning

confidence: 99%

Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome: Erratum

2017

Anesthesia &Amp; Analgesia

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BACKGROUND-Bisphosphonates are used to prevent the bone loss and fractures associated with osteoporosis, bone metastases, multiple myeloma, and osteogenis deformans. Distal limb fractures cause regional bone loss with cutaneous inflammation and pain in the injured limb that can develop into complex regional pain syndrome (CRPS). Clinical trials have reported that antiresorptive bisphosphonates can prevent fracture-induced bone loss, inhibit serum inflammatory cytokine levels, and alleviate CRPS pain. Previously we observed that the inhibition of inflammatory cytokines or adaptive immune responses attenuated the development of pain behavior in a rat fracture model of CRPS and we hypothesized that bisphosphonates could prevent pain behavior, trabecular bone loss, post-fracture cutaneous cytokine up-regulation, and adaptive immune responses in this CRPS model.

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“…Therefore, blocking NGF with antagonists has been suggested to provide relief from pain. This prediction has now been borne out by a number of studies using anti-NGF antibodies and Fc-receptor fusion proteins (18)(19)(20)(21). The absence of neurotrophins and their receptors from Drosophila and Caenorhabditis elegans indicates that they must subserve higher-order functions (16).…”

Section: Introductionmentioning

confidence: 98%

A Conversation with Rita Levi-Montalcini

Chao

2010

Annu. Rev. Physiol.

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There are very few proven theories that exist in biology. One that has stood the test of time is the neurotrophic theory. It explains why only half of the neurons produced early in development are needed to form a functional nervous system. The explanation came from the discovery of nerve growth factors (NGFs), which help nourish neurons, guide their axons to their proper connections, and prevent cell death. Rita Levi-Montalcini, who formulated this idea, celebrated her 100th birthday on April 22, 2009 in Rome. I had the opportunity to interview her at the European Brain Research Institute (EBRI) in September 2008, which forms the basis of this article. Shortly after the interview, Rita attended the International NGF meeting, held in the Upper Galilee region of Israel (Kfar Blum, Israel). Despite her age, she traveled to the meeting by flying to Tel Aviv and taking a 4-h car ride to the conference site. Remarkably, she participated in the meeting by giving a 30-min talk and sponsoring a poster (see Figure 1 ).

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Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I

Cited by 108 publications

References 59 publications

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Orthopedic surgery modulates neuropeptides and BDNF expression at the spinal and hippocampal levels

Bisphosphonates Inhibit Pain, Bone Loss, and Inflammation in a Rat Tibia Fracture Model of Complex Regional Pain Syndrome: Erratum

A Conversation with Rita Levi-Montalcini

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