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The Glial–Neuronal GRK2 Pathway Participates in the Development of Trigeminal Neuropathic Pain in Rats

Published:November 11, 2013DOI:https://doi.org/10.1016/j.jpain.2013.10.013

      Abstract

      This study examined the role of the glial–neuronal G protein–coupled receptor kinase 2 (GRK2) pathway in the development of trigeminal neuropathic pain. Male Sprague Dawley rats, weighing 220 to 240 g, were anesthetized with ketamine (0.2 g/kg) and xylazine (0.02 g/kg). Under anesthesia, the left lower second molar was extracted, followed by the placement of a mini–dental implant to intentionally injure the inferior alveolar nerve. This injury produced mechanical allodynia along with the downregulation of neuronal GRK2 expression in the medullary dorsal horn. On the other hand, early intracisternal treatment with MDL28170, a calpain inhibitor, produced prolonged antiallodynic effects and blocked this downregulation of neuronal GRK2 expression. The intracisternal infusion of minocycline, a microglia inhibitor, and l-α-aminoadipic acid, an astrocytic specific inhibitor, also blocked the induced mechanical allodynia and downregulated neuronal GRK2 expression, respectively. Double immunofluorescence showed that the interleukin (IL)-1β and IL-1R signals colocalize with the astrocytes and neurons, respectively, in the medullary dorsal horn following an inferior alveolar nerve injury. In addition, the intracisternal infusion of an IL-1 receptor antagonist also produced antiallodynic effects and blocked the downregulation of neuronal GRK2 expression. These results suggest that the glial–neuronal GRK2 pathway is a potentially important new target for treating neuropathic pain. Moreover, the IL-1β expressed in astrocytes plays a significant role in modulating this pathway.

      Perspective

      This study showed that the glial–neuronal GRK2 pathway participates in the development of trigeminal neuropathic pain in rats. These results suggest that the glial–neuronal GRK2 pathway is a potentially important new target for the treatment of neuropathic pain.

      Key words

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