Cellular and molecular neurobiology
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Cell. Mol. Neurobiol. · Jan 2014
Involvement of spinal chemokine CCL2 in the hyperalgesia evoked by bone cancer in mice: a role for astroglia and microglia.
The hypernociceptive role played by the chemokine CCL2, and its main receptor, CCR2, in pathological settings is being increasingly recognized. We aimed to characterize the involvement of spinal CCL2 in the hyperalgesia due to the intratibial inoculation of fibrosarcoma NCTC 2472 cells in mice. The intrathecal (i.t.) administration of the CCR2 antagonist RS 504393 (1–3 μg) or an anti-CCL2 antibody inhibited tumoral hyperalgesia. ⋯ GFAP, but not Iba-1, up-regulation was reduced in tumor-bearing mice treated for 3 days with i.t. RS 504393, indicating that spinal CCL2 acts as an astroglial activator in this setting. The participation at spinal level of CCL2/CCR2 in tumoral hypernociception, together with its previously described involvement at periphery, makes attractive the modulation of this system for the alleviation of neoplastic pain.
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Cell. Mol. Neurobiol. · Jan 2014
Altered mitochondrial ATP synthase expression in the rat dorsal root ganglion after sciatic nerve injury and analgesic effects of intrathecal ATP.
Mitochondrial ATP synthase has multiple interdependent biological functions in neurons. Among them, ATP generation and regulation are the most important. The present study investigated whether the expression of mitochondrial ATP synthase correlates with symptoms of neuropathic pain in adult rats after axotomy, and whether intrathecal ATP administration is therapeutic in these neuropathic rats. ⋯ After nerve injury, the expression of mitochondrial ATP synthase was decreased in protein extracts and was found mainly in C-fiber and A-δ fiber neurons of the DRGs. The decreased expression of mitochondrial ATP synthase and its subcellular localization were related to thermal and mechanical hyperalgesia. Administration of intrathecal ATP significantly attenuated thermal and mechanical hypersensitivity throughout the experimental period, which suggests its potential role in the treatment of neuropathic pain.