Functional expression of glycine receptors in DRG neurons of mice

Glycine receptor is one of the chloride-permeable ion channels composed of combinations of four ? subunits and one ? subunit. In adult spinal cord, the glycine receptor ?1 subunit is crucial for the generation of inhibitory neurotransmission. The reduced glycinergic inhibition is regarded as one of the key spinal mechanisms underlying pathological pain symptoms. However, the expression and function of glycine receptors in the peripheral system are largely unknown as yet. Here we found that glycine receptor ?1 subunit was prevalent in the dorsal root ganglia (DRG) neurons as well as in the sciatic nerves of adult mice. Intraganglionar or intraplantar injection of glycine receptor antagonist strychnine caused the hypersensitivity to mechanical, thermal and cold stimuli, suggesting the functional importance of peripheral glycine receptors in the control of nociceptive signal transmission. Our data showed that peripheral inflammation induced by formalin decreased the expression of glycine receptor ?1 subunit on the plasma membrane of DRG neurons, which was attributed to the activation of protein kinase C signaling. Intraplantar application of glycine receptor agonist glycine or positive modulator divalent zinc ion alleviated the first-phase painful behaviors induced by formalin. These data suggested that peripheral glycine receptor might serve as an effective target for pain therapy.

Automated summary

The glycine receptor, consisting of α1 subunits, plays a crucial role in inhibitory neurotransmission and may serve as an effective target for pain therapy in the peripheral nervous system. Inflammation in the periphery can reduce the expression of glycine receptors on the plasma membrane of neurons. Glycine receptor agonists or positive modulators show promise in alleviating pain behaviors induced by inflammation.