Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold

Albisetti, Gioele W.; Ganley, Robert P.; Pietrafesa, Francesca; Werynska, Karolina; Sousa, Marília; Sipione, Rebecca; Scheurer, Louis; Bösl, Michael R.; Pelczar, Pawel; Wildner, Hendrik; Zeilhofer, Hanns Ulrich

doi:10.1016/j.neuron.2022.10.008

Cited by 9 publications

(6 citation statements)

References 69 publications

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“…Activation of PV-expressing inhibitory interneurons reduced inflammatory and neuropathic mechanical allodynia, but had no effect on heat hypersensitivity ( Petitjean et al, 2015 ). A recent study by Albisetti et al, 2023 found that activating a population of dorsal horn inhibitory interneurons defined by expression of Kcnip2 suppressed cold allodynia in a neuropathic model. However, our findings apparently provide the first evidence that activating dorsal horn inhibitory interneurons can suppress heat hypersensitivity, in addition to cold and mechanical allodynia, in persistent pain states.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

Boyle

Polgár

Gutièrrez‐Mecinas

et al. 2023

eLife

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Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here we investigate the role of interneurons that continue to express NPY (NPY-INs) in adulthood. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen- evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY- IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.

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Section: Discussionmentioning

confidence: 99%

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

Boyle

Polgár

Gutièrrez‐Mecinas

et al. 2023

eLife

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“… 23 We therefore chose intersectional strategies to selectively target the excitatory or inhibitory c-Maf neuron family in the spinal cord. To this end, we crossed either a Lmx1β Dre allele ( Figure S2 ) or a GlyT2:Dre transgene 24 into c-Maf Cre mice, and employed Cre and Dre double-dependent reporter transgenes delivered via recombinant adeno-associated viruses (rAAVs) ( Figures 2 A and 2J). Lmx1β is expressed in the vast majority of dorsal horn excitatory neurons, whereas GlyT2 is a marker gene for inhibitory neurons of the deep dorsal horn.…”

Section: Resultsmentioning

confidence: 99%

“…GlyT2:Dre mice were generated using the same strategy as for the GlyT2:eGFP and GlyT2:Cre mouse lines. 24 , 25 , 64 For further details on the genetically modified mice used in this study, see KRT.…”

Section: Methodsmentioning

confidence: 99%

c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy

Frezel¹,

Ranucci²,

Foster³

et al. 2023

Cell Reports

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“…Activation of PV- expressing inhibitory interneurons reduced inflammatory and neuropathic mechanical allodynia, but had no effect on heat hypersensitivity 15 . A recent study by Albisetti et al 61 found that activating a population of dorsal horn inhibitory interneurons defined by expression of Kcnip2 suppressed cold allodynia in a neuropathic model. However, our findings apparently provide the first evidence that activating dorsal horn inhibitory interneurons can suppress heat hypersensitivity, in addition to cold and mechanical allodynia, in persistent pain states.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

Boyle

Polgár

Gutièrrez‐Mecinas

et al. 2023

Preprint

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Somatosensory information is processed by a complex network of interneurons in the spinal dorsal horn. It has been reported that inhibitory interneurons that express neuropeptide Y (NPY), either permanently or during development, suppress mechanical itch, with no effect on pain. Here we investigate the role of interneurons that continue to express NPY (NPY-INs) in adulthood. We find that chemogenetic activation of NPY-INs reduces behaviours associated with acute pain and pruritogen evoked itch, whereas silencing them causes exaggerated itch responses that depend on cells expressing the gastrin-releasing peptide receptor. As predicted by our previous studies, silencing of another population of inhibitory interneurons (those expressing dynorphin) also increases itch, but to a lesser extent. Importantly, NPY IN activation also reduces behavioural signs of inflammatory and neuropathic pain. These results demonstrate that NPY-INs gate pain and itch transmission at the spinal level, and therefore represent a potential treatment target for pathological pain and itch.

show abstract

Inhibitory Kcnip2 neurons of the spinal dorsal horn control behavioral sensitivity to environmental cold

Cited by 9 publications

References 69 publications

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

c-Maf-positive spinal cord neurons are critical elements of a dorsal horn circuit for mechanical hypersensitivity in neuropathy

Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling

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