POSSIBLE INVOLVEMENT OF SYNTAXIN 1A DOWNREGULATION IN THE LATE PHASE OF ALLODYNIA INDUCED BY PERIPHERAL NERVE INJURY

Syntaxin 1A is a membrane protein playing an integral role in exocytosis and membrane trafficking. The superficial dorsal horn (SDH) of the spinal cord, where nociceptive synaptic transmission is modulated, is rich in this protein. We recently reported that peripheral nerve ligation-induced nociceptive responses are considerably enhanced in syntaxin 1A-knockout mice [Takasusuki T, Fujiwara T, Yamaguchi S, Fukushima T, Akagawa K, Hori Y (2007) Eur J Neurosci 26:2179-2187]. On the basis of this earlier finding, we hypothesized that syntaxin 1A is involved in peripheral nerve injury-induced nociceptive plasticity. In this study, we examined this hypothesis by using nociceptive behavioral studies and tight-seal whole-cell recordings from neurons in the SDH of adult mouse spinal cord slices. Partial sciatic nerve ligation (PSNL) in adult male Institute of Cancer Research (ICR) mice increased the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs). The amplitude of the mEPSCs did not exhibit any changes, suggesting that peripheral nerve injury is associated with increased synaptic release of excitatory neurotransmitters. Western blot and real-time quantitative reverse transcription-polymerase chain reaction analyses revealed that PSNL gradually decreased the expression level of syntaxin 1A in the spinal SDH. This downregulation of syntaxin 1A took several days to develop, whereas behavioral allodynia developed within one day after PSNL. Syntaxin 1A knockdown by intrathecal injection of an antisense oligodeoxynucleotide against the syntaxin 1A gene led to the gradual development of allodynia. These results indicate a possible involvement of syntaxin 1A downregulation in the late maintenance phase of peripheral nerve injury-induced allodynia. In addition, syntaxin 1A knockdown by ribonucleic acid interference enhanced the axonal elongation and sprouting of spinal dorsal horn neurons in culture, suggesting that PSNL-induced syntaxin 1A downregulation may result in the rearrangement of the synaptic connections between neurons in the spinal dorsal horn. Taken together, it is possible to conclude that syntaxin 1A might be involved in spinal nociceptive plasticity induced by peripheral nerve injury. (c) 2011 AGA Institute. Published by Elsevier Ltd. All rights reserved.