336회 Spinal substantia gelatinosa neurons as gain and loss function of…

336회

연사 : 김 상 정, 강원대학교 의과대학 생리학교실

제목:  Spinal substantia gelatinosa neurons as gain and loss function of pain transmission

Abstract

Substantia gelatinosa (SG) neurons of spinal cord receive the synaptic inputs from pain-transmitting primary afferent neurons and integrate the noxious information. The excitability of these neurons determines the gain or loss function of pain in spinal cord. First part of my talk is on the loss function of pain. The cellular analgesic mechanism of opioid is known to decrease the excitability of SG neurons by increasing inward rectifying K+ current (IKir). We performed the whole-cell tight seal recording in the transverse slice of pup spinal cord to observed the effect of opioid on voltage-insensitive K+ current (IK(L)) in rat SG neurons. Current-voltage (I-V) relationship revealed three types of non-inactivating sustained membrane currents: IK(L), IKir and Ih. The contribution of these currents to total membrane current was variable between cells. DAMGO, a μ-opioid agonist, caused a robust and repeatable hyperpolarization in current clamp or outward current in voltage-clamp in SG neurons lacking Ih (n=25). The I-V relationship of the DAMGO-sensitive current was diverse. Half of neurons (n=13) exhibited a linear relationship suggesting DAMGO opens IK(L). In 3 neurons the slope conductance at ?50 mV was almost null exhibiting pure inward rectification (IKir). In rest of neurons DAMGO-sensitive current was mixture of IK(L) and IKir. The hyperpolarization by DAMGO at resting membrane potential and subsequent decrease in membrane excitability of SG neurons appears to be carried by IK(L) in addition to IKir. Hyperalgesia is the increased response of dorsal horn neuron to the noxious stimulation after the injury of tissue. This is a gain function of pain. The key to understand the mechanism of hyperalgesia is the synaptic plasticity between primary afferent and SG neuron. Long-term potentiation (LTP) is the present mechanism of synaptic plasticity to explain the learning and memory in hippocampus. Interestingly, LTP is also observed in the synapse between primary afferent and SGN. Here we examine this issue by using techniques that maximize the likelihood of stimulating a single axon and thereby presumably a single synapse before and after the induction of LTP. A release failure and a success were clearly distinguished in whole-cell recording mode. The pairing stimulation model induced LTP where low-frequency stimulation was paired with a postsynaptic depolarization. LTP was presented as an increase in the synaptic strength, a decrease in the synaptic failure and no discernible change in the potency. LTP was blocked by the presence of NMDA receptor antagonist, D-AP5, and by clamping potential around the resting membrane potential during the paring stimulation. These results suggest that the mechanism for the expression of LTP in SGN involves an increase in reliability and is difficult to explain by an increase in potency.