Role of Connexin 36 in the Development of Neuropathic Pain (21912)
In contrast to acute pain, pathological chronic pain has no biological purpose or set endpoint and is often not well relieved by common analgesics. Changes that drive the development of chronic pain are mediated by complex interactions between neurons and glial cells. These cells rapidly communicate with each other through gap junctions, including Connexin36 (Cx36). In this study we investigated the role of Cx36 in pain signaling using Cx36 knockout mice. We generated a number of neuropathic pain models in Cx36 KO mice wild-type littermate controls, including sciatic nerve injury, chemotherapy-induced neuropathy, reserpine-induced fibromyalgia, and streptozotocin-induced diabetic neuropathy. Sensitivity to touch, heat and cold were tested. Data showed significant decreases in mechanical allodynia using a von Frey assay in the Cx36 KO mice in the weeks following pain development. Spinal cords were harvested for immunohistochemical labeling, which showed a decrease in microglial activation in the KO group. Electrophysiological analysis using dual whole-cell patch clamp recording techniques in spinal cord slices showed gap-junction-mediated electrical synaptic transmission and electrotonic coupling between neurons in wild-type mice was absent in Cx36 KO mice, electrotonic coupling driving synchronous firing and burst firing patterns of activity. This data suggests that targeting the Cx36 hemichannels may be an effective therapeutic option for the treatment of neuropathic pain conditions.