Involvement of sensory nerves and immune cells in osteophyte formation in the ankle joint of adjuvant arthritic rats

Wu, Zhou; Nagata, Kazuhiro; Iijima, Tadahiko

doi:10.1007/s00418-002-0443-x

Cited by 38 publications

(17 citation statements)

References 45 publications

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“…For example, prior studies have reported that in humans with chronic discogenic pain there is growth of CGRP + nerve fibers into normally aneural and avascular areas of the intervertebral disc 107 . Other studies have demonstrated significant sprouting of CGRP + nerve fibers following bone fracture in rat and in the arthritic joints of humans and animals 108–111 . These reports suggest that following injury or disease of the skeleton, significant sprouting of TrkA + nerve fibers can occur, and it appears that endogenous stromal, inflammatory and immune cells are a major source of NGF 68,105,106 .…”

Section: Ngf/trka Induced Sprouting and Neuroma Formationmentioning

confidence: 90%

Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

et al. 2011

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Nerve growth factor (NGF) was originally discovered as a neurotrophic factor essential for the survival of sensory and sympathetic neurons during development. However in the adult, NGF has been found to play an important role in nociceptor sensitization following tissue injury. Here we outline mechanisms by which NGF activation of its cognate receptor, tropomyosin-related kinase A receptor, regulates a host of ion channels, receptors, and signaling molecules to enhance acute and chronic pain. Further, we document that peripherally restricted antagonism of NGF-tropomyosin-related kinase A receptor signaling is effective for controlling human pain while appearing to maintain normal nociceptor function. Understanding whether there are any unexpected adverse events as well as how humans may change their behavior and use of the injured/degenerating tissue following significant pain relief without sedation will be required to fully appreciate the patient populations that may benefit from these therapies targeting NGF.

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Section: Ngf/trka Induced Sprouting and Neuroma Formationmentioning

confidence: 90%

Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

et al. 2011

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“…Studies including osteoarthritis, temporomandibular joint disorder, and degenerative intervertebral disc (IVD) have also reported the sprouting of sensory and sympathetic nerve fibers into normally avascular, cartilaginous tissue [15,23,24,39,40,42,50,89,96]. Studies have also reported sprouting of CGRP + , Substance P + , and GAP43 + nerve fibers into the callus that forms around the bone fracture in rats [35,58,59] and in the synovium of arthritic joints of humans and mammals [13,94,100]. Furthermore, it is well documented in sarcoma, prostate, and breast cancers in bone that there is ectopic sprouting of sensory and sympathetic nerve fibers in the bone marrow, mineralized bone, and periosteum [10,27,38].…”

Section: Discussionmentioning

confidence: 99%

Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain

Chartier

Thompson

Longo

et al. 2014

Pain

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Skeletal injury is a leading cause of chronic pain and long-term disability worldwide. While most acute skeletal pain can be effectively managed with nonsteroidal anti-inflammatory drugs and opiates, chronic skeletal pain is more difficult to control using these same therapy regimens. One possibility as to why chronic skeletal pain is more difficult to manage over time is that there may be nerve sprouting in non-healed areas of the skeleton that normally receive little (mineralized bone) to no (articular cartilage) innervation. If such ectopic sprouting did occur, it could result in normally nonnoxious loading of the skeleton being perceived as noxious and/or the generation of a neuropathic pain state. To explore this possibility, a mouse model of skeletal pain was generated by inducing a closed fracture of the femur. Examined animals had comminuted fractures and did not fully heal even at 90+ days post fracture. In all mice with nonhealed fractures, exuberant sensory and sympathetic nerve sprouting, an increase in the density of nerve fibers, and the formation of neuroma-like structures near the fracture site were observed. Additionally, all of these animals exhibited significant pain behaviors upon palpation of the nonhealed fracture site. In contrast, sprouting of sensory and sympathetic nerve fibers or significant palpation-induced pain behaviors was never observed in naïve animals. Understanding what drives this ectopic nerve sprouting and the role it plays in skeletal pain may allow a better understanding and treatment of this currently difficult-to-control pain state.

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“…The specimens were cryoprotected 2 days in 30% sucrose in phosphate-buffered saline and then were embedded in an optimal cutting temperature compound (Sakura Finetechnical Co., Ltd., Tokyo, Japan). Serial coronal frozen sections (14 μ m) were subjected to the immunohistochemical analyses [34, 35]. …”

Section: Methodsmentioning

confidence: 99%

Leptomeningeal Cells Transduce Peripheral Macrophages Inflammatory Signal to Microglia in Reponse toPorphyromonas gingivalisLPS

Liu

Zhang

et al. 2013

Mediators of Inflammation

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We report here that the leptomeningeal cells transduce inflammatory signals from peripheral macrophages to brain-resident microglia in response to Porphyromonas gingivalis (P.g.) LPS. The expression of Toll-like receptor 2 (TLR2), TLR4, TNF-α, and inducible NO synthase was mainly detected in the gingival macrophages of chronic periodontitis patients. In in vitro studies, P.g. LPS induced the secretion of TNF-α and IL-1β from THP-1 human monocyte-like cell line and RAW264.7 mouse macrophages. Surprisingly, the mean mRNA levels of TNF-α and IL-1β in leptomeningeal cells after treatment with the conditioned medium from P.g. LPS-stimulated RAW264.7 macrophages were significantly higher than those after treatment with P.g. LPS alone. Furthermore, the mean mRNA levels of TNF-α and IL-1β in microglia after treatment with the conditioned medium from P.g. LPS-stimulated leptomeningeal cells were significantly higher than those after P.g. LPS alone. These observations suggest that leptomeninges serve as an important route for transducing inflammatory signals from macrophages to microglia by secretion of proinflammatory mediators during chronic periodontitis. Moreover, propolis significantly reduced the P.g. LPS-induced TNF-α and IL-1 β production by leptomeningeal cells through inhibiting the nuclear factor-κB signaling pathway. Together with the inhibitory effect on microglial activation, propolis may be beneficial in preventing neuroinflammation during chronic periodontitis.

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Involvement of sensory nerves and immune cells in osteophyte formation in the ankle joint of adjuvant arthritic rats

Cited by 38 publications

References 45 publications

Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

Antagonism of Nerve Growth Factor-TrkA Signaling and the Relief of Pain

Exuberant sprouting of sensory and sympathetic nerve fibers in nonhealed bone fractures and the generation and maintenance of chronic skeletal pain

Leptomeningeal Cells Transduce Peripheral Macrophages Inflammatory Signal to Microglia in Reponse toPorphyromonas gingivalisLPS

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