| Mrg (Mas-related gene receptors) is one of members of the G protein-coupled receptor family, rat MrgC receptors are exclusively expressed in a subset of small-diameter neurons in trigeminal and dorsal root ganglia (DRG). It has been demonstrated bovine adrenal medulla 8-22 (BAM8-22), a derivative of endogenous opioid peptide BAM22, and selective MrgC receptor agonist. Intrathecal injection of BAM8-22 inhibited hyperalgesia in inflammatory rats. It is reported that astrocytes play an important role on the maintenance of bone cancer pain. The activation of astrocytes and immune cells release inflammatory cytokines IL-1β, and CGRP, nNOS may be involved in the maintenance of bone cancer pain.This study application of noxious thermal stimulation, mechanical stimulation and imaging methods to identify the establishment of bone cancer pain model. Based on the model of bone cancer pain, used of the behavioral and fluorescent immune-histochemical staining techniques to examine:(1) The effects of intrathecal administration of BAM8-22 on bone cancer pain induced mechanical allodynia; (2) The effects of the expression of GFAP positive cells after intrathecal injection BAM8-22 on rats of bone cancer pain in the spinal; (3) The change of IL-1β, CGRP and nNOS positive cells expression after intrathecal injection BAM8-22 on rats of bone cancer pain in DRG.The results showed:(1) Used of Walker 256 breast cancer cells established the model of bone cancer pain successfully, the rats appeared to thermal hyperalgesia and mechanical allodynia. (2) The rats of bone cancer pain appeared to allodynia on 6th day after surgery, and it is maintained to 16 days obviously. Activation MrgC receptors by intrathecal injection of BAM8-22 remarkably increased the mechanical withdrawal threshold, length of times about 80 min, and also prolong mechanical basic threshold obviously. (3) The bone cancer pain can caused the expression increased significantly of GFAP positive cells in the spinal, and cell bodies are hypertrophy proliferation; Intrathecal administration of BAM8-22 reduced significantly the expression of GFAP in spinal cord. (4) Intrathecal administration of BAM8-22 remarkably attenuated bone cancer pain-evoked increase in IL-1β, CGRP and nNOS positive neurons in the DRG.These results suggest that Mrg receptors play a role on anti-hypersensitivity and antinociception. It is possible mechanism through inhibiting the activation of astrocytes in the spinal cord, as well as the modulation of pro-nociceptive mediators IL-1β, CGRP and nNOS in DRG underlies the inhibition of mechanical allodynia by MrgC receptor activation. |
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