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Melzak and Wall(Science,1965)proposed a well-known hypothesis,the gate theory of pain,which is highly influential for nearly 50 years.However,the theory remains a conjecture because of insufficient evidence to substantiate the neural circuitry underlying pain signaling and modulation in the spinal dorsal horn.Our recent study(Lu et al.J Clin Invest.2013)found that the spinal dorsal horn contains a feed-forward inhibitory circuit that can gate incoming low-threshold Aβ input to nociceptive pathway.This study identified a novel “gate” with definite morphological and functional details in the spinal dorsal horn,in which activation of low-threshold innocuous Aβ fibers in neuropathic pain condition “opens” the gate to elicit mechanical allodynia.This “allodynia gate” may contribute to the development of neuropathic pain.The present study utilized patch-clamp whole-cell recordings,morphological and behavior techniques examined the contribution of LTD in the “allodynia gate” circuits to the development of neuropathic allodynia induced by peripheral nerve injury in SD rat.We found that the peripheral nerve injury induced the endocytosis of postsynaptic glutamate AMPA receptors of glycinergic neurons,and involved in the development of the circuit-specific LTD in synapses between low-threshold innocuous Aβ fibers and glycinergic neurons,and finally,open the “allodynia gate”.We proposed that the GluR2 endocytosis of glycinergic neurons is required for the LTD induction in the feed-forward spinal inhibitory circuit; this circuit-specific LTD may contribute to the development of neuropathic allodynia induced by peripheral nerve injury.