Journal
PAIN
Volume 163, Issue 3, Pages E432-E452Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/j.pain.0000000000002422
Keywords
presynaptic inhibition; postsynaptic inhibition; parvalbumin; allodynia; circuits; optogenetics; brainbow
Categories
Funding
- National Health and Medical Research Council (NHMRC) of Australia [631000, 1043933, 1144638, 1184974]
- Hunter Medical Research Institute
- BBSRC [BB/P007996/1]
- BBSRC [BB/P007996/1] Funding Source: UKRI
- National Health and Medical Research Council of Australia [1184974, 1144638] Funding Source: NHMRC
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Excitatory parvalbumin-expressing interneurons (ePVINs) in the spinal dorsal horn play an important role in sensory processing and form synaptic connections among and between inhibitory PVIN populations. They contribute to neuronal networks within several distinct circuits and their aberrant activity may contribute to the development of mechanical hypersensitivity.
Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here, we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported and that both ePVIN and inhibitory PVIN populations form synaptic connections among (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.
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