Downregulation of connexin36 in mouse spinal dorsal horn neurons leads to mechanical allodynia

摘要: Connexin36 (Cx36), a component of neuronal gap junctions, is crucial for interneuronal communication and regulation. Gap junction dysfunction underlies neurological disorders, including chronic pain. Following peripheral nerve injury, Cx36 expression in the ipsilateral spinal dorsal horn was markedly decreased over time, which paralleled time course hind paw tactile allodynia. Intrathecal (i.t.) injection siRNA (1 5 pg) significantly reduced protein lumbar cord, peaking 3 days after injection, corresponded with onset It possible that some allodynia resulting from downregulation could be mediated through excitatory neuromodulators, such as glutamate substance P. The knockdown-evoked attenuated by i.t. treatment N-methyl-D-aspartate receptor antagonist MK-801 but not P CP96345. Immunohistochemistry showed colocalized glycine transporter-2, marker inhibitory glycinergic interneurons, decarboxylase 67, GABAergic interneurons. results indicate inhibition interneurons reduced, leading to increased glutamatergic neurotransmission, result downregulation. current data suggest neuropathic pain further novel target development analgesics. © 2014 Wiley Periodicals, Inc.