Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain

Peters, Christopher M.; Ghilardi, Joseph R.; Keyser, Cathy P.; Kubota, Kazufumi; Lindsay, Theodore H.; Luger, Nancy M.; Mach, David B.; Schwei, Matthew J.; Sevcik, Molly A.; Mantyh, Patrick W.

doi:10.1016/j.expneurol.2004.11.028

Cited by 184 publications

(140 citation statements)

References 89 publications

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“…Our evidence that gabapentin had no effect in control neurons but attenuated responses in DRG neurons affected by fibrosarcoma cells is consistent with changes in DRG neurons from transgenic mice overexpressing the ␣2␦1 subunit (Li et al, 2006). Furthermore, the antihyperalgesic effect of gabapentin is consistent with a previous report in which gabapentin ameliorated movement-associated pain in a model of murine bone cancer (Peters et al, 2005) and lends additional support to the use of gabapentin in treatment of cancer pain.…”

Section: Discussionsupporting

confidence: 90%

Chemical Interactions between Fibrosarcoma Cancer Cells and Sensory Neurons Contribute to Cancer Pain

Khasabova¹,

Stucky²,

Harding-Rose³

et al. 2007

J. Neurosci.

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Section: Discussionsupporting

confidence: 90%

Chemical Interactions between Fibrosarcoma Cancer Cells and Sensory Neurons Contribute to Cancer Pain

Khasabova¹,

Stucky²,

Harding-Rose³

et al. 2007

J. Neurosci.

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“…One, four, six and ten days following the initial paclitaxel (n≥5 in each time point) or vehicle administration (n≥4 in each time point), animals were sacrificed and the tissue was processed for immunohistochemical analysis as previously described (Peters et al, 2005). Briefly, rats were perfused intracardially with 200 ml of 0.1 M phosphate buffered saline (PBS) followed by 200 ml of 4% formaldehyde/12.5% picric acid solution in 0.1 M PBS.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The number of ATF3 positive cellular profiles in L4 DRG was determined as previously reported (Peters et al, 2005). The cell size distribution of ATF3 in neuronal subsets was determined by measuring the soma area (Image Pro Plus v 3.0) of individual ATF3 and NeuN positive profiles in three paclitaxel-treated rats per each time point.…”

Section: Quantification/ Image Analysismentioning

confidence: 99%

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

et al. 2007

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Paclitaxel (Taxol®) is a frontline antineoplastic agent used to treat a variety of solid tumors including breast, ovarian, or lung cancer. The major dose limiting side effect of paclitaxel is a peripheral sensory neuropathy that can last days to a lifetime. To begin to understand the cellular events that contribute to this neuropathy, we examined a marker of cell injury/regeneration (activating transcription factor 3; ATF3), macrophage hyperplasia/hypertrophy; satellite cell hypertrophy in the dorsal root ganglion (DRG) and sciatic nerve as well as astrocyte and microglial activation within the spinal cord at 1, 4, 6 and 10 days following intravenous infusion of therapeutically relevant doses of paclitaxel. At day 1 post-infusion there was an up-regulation of ATF3 in a subpopulation of large and small DRG neurons and this up-regulation was present through day 10. In contrast, hypertrophy of DRG satellite cells, hypertrophy and hyperplasia of CD68+ macrophages in the DRG and sciatic nerve, ATF3 expression in S100β+ Schwann cells and increased expression of the microglial marker (CD11b) and the astrocyte marker glial fibrillary acidic protein in the spinal cord were not observed until day 6 post infusion. The present results demonstrate that using the time points and markers examined, DRG neurons show the first sign of injury which is followed days later by other neuropathological changes in the DRG, peripheral nerve and dorsal horn of the spinal cord. Understanding the cellular changes that generate and maintain this neuropathy may allow the development of mechanism-based therapies to attenuate or block this frequently painful and debilitating condition.

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“…Although bone marrow cells fill the intramedullary space in the normal mouse femur, they are largely replaced by tumor cells in the femur at day 14 after osteosarcoma injection ( Figure 1). This model features a reproducible pattern and rate of tumor growth within the intramedullary cavity following implantation of sarcoma cells [2]. Figure 2 shows pain-related behavior before and at day 7, day 14 and day 21 after sarcoma or sham injection.…”

Section: Murine Model Of Bone Cancer Painmentioning

confidence: 97%

Reduction of bone cancer pain by CB1 activation and TRPV1 inhibition

et al. 2010

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Tumor-induced injury of primary afferent sensory nerve fibers in bone cancer pain

Cited by 184 publications

References 89 publications

Chemical Interactions between Fibrosarcoma Cancer Cells and Sensory Neurons Contribute to Cancer Pain

Chemical Interactions between Fibrosarcoma Cancer Cells and Sensory Neurons Contribute to Cancer Pain

An evolving cellular pathology occurs in dorsal root ganglia, peripheral nerve and spinal cord following intravenous administration of paclitaxel in the rat

Reduction of bone cancer pain by CB1 activation and TRPV1 inhibition

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