A UT Dallas scientist has found a new neurological mechanism that appears to contribute to a reduction in pain. The discovery of neuroligin-2 as a cause exacerbating chronic pain is significant for the research community.
Normally a GABA neurotransmitter acts to inhibit neuronal activity, such as pain. However, when pain becomes chronic there is strong evidence that a process called GABAergic plasticity can cause GABA to lose its inhibitory activity, sometimes making the pain even worse.
The source of these excitatory actions in neuronal circuits has been broadly attributed to chloride ions, but new research has found another potential cause of GABAergic plasticity: synaptic adhesion molecules called neuroligin-2. Authors observed increased neuroligin (nlgn) 2 expression in the spinal dorsal horn.
This protein increase was associated with an increase in nlgn2A splice variant mRNA, which promotes inhibitory synaptogenesis. Disruption of nlgn2 function with the peptide inhibitor, neurolide 2, produced mechanical hypersensitivity in naive mice but reversed hyperalgesic priming in mice previously exposed to brain-derived neurotrophic factor (BDNF). Neurolide 2 treatment also reverses the change in polarity in GABAergic pharmacology observed in the maintenance of hyperalgesic priming.
These observations reveal new mechanisms involved in the spinal maintenance of a pain plasticity and further suggest that disinhibitory mechanisms are central features of neuroplasticity in the spinal dorsal horn.
Potential new source for pain inhibition
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