Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli

Gutièrrez‐Mecinas, María; Bell, Alasdair F.; Marin, Alina; Taylor, Rebecca S.; Boyle, Kieran A.; Furuta, Takeshi; Watanabe, Masahiko; Polgár, Erika; Todd, Andrew J.

doi:10.1097/j.pain.0000000000000778

Cited by 59 publications

(104 citation statements)

References 98 publications

(173 reference statements)

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“…In sections from Tac1 Cre mice that had been injected with AAV.flex. eGFP, we found a similar distribution of eGFP-labeled (Tac1-expressing) cells to that described previously (Dickie et al, 2019;Gutierrez-Mecinas et al, 2017). These were concentrated in laminae I and II, with labeled cells scattered through the deeper dorsal horn.…”

Section: Partial Overlap Between Cck and Substance P Populationssupporting

confidence: 88%

Expression of cholecystokinin by neurons in mouse spinal dorsal horn

Gutièrrez‐Mecinas

Bell

Shepherd

et al. 2019

J of Comparative Neurology

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Excitatory interneurons account for the majority of dorsal horn neurons, and are required for perception of normal and pathological pain. We have identified largely non‐overlapping populations in laminae I‐III, based on expression of substance P, gastrin‐releasing peptide, neurokinin B, and neurotensin. Cholecystokinin (CCK) is expressed by many dorsal horn neurons, particularly in the deeper laminae. Here, we have used immunocytochemistry and in situ hybridization to characterize the CCK cells. We show that they account for ~7% of excitatory neurons in laminae I‐II, but between a third and a quarter of those in lamina III. They are largely separate from the neurokinin B, neurotensin, and gastrin‐releasing peptide populations, but show limited overlap with the substance P cells. Laminae II‐III neurons with protein kinase Cγ (PKCγ) have been implicated in mechanical allodynia following nerve injury, and we found that around 50% of CCK cells were PKCγ‐immunoreactive. Neurotensin is also expressed by PKCγ cells, and among neurons with moderate to high levels of PKCγ, ~85% expressed CCK or neurotensin. A recent transcriptomic study identified mRNA for thyrotropin‐releasing hormone in a specific subpopulation of CCK neurons, and we show that these account for half of the CCK/PKCγ cells. These findings indicate that the CCK cells are distinct from other excitatory interneuron populations that we have defined. They also show that PKCγ cells can be assigned to different classes based on neuropeptide expression, and it will be important to determine the differential contribution of these classes to neuropathic allodynia.

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Section: Partial Overlap Between Cck and Substance P Populationssupporting

confidence: 88%

Expression of cholecystokinin by neurons in mouse spinal dorsal horn

Gutièrrez‐Mecinas

Bell

Shepherd

et al. 2019

J of Comparative Neurology

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“…The strategy used to ablate SP + neurons in this study presumably captured both interneurons and lamina I ALT projection neurons, making it difficult to distinguish their relative contributions. In addition, a minority of SP + cells are inhibitory (Gutierrez-Mecinas et al 2017) and ablating these cells may have contributed to the behavior. Finally, some excitatory interneurons (including many of the PKCγ + cells in laminae II-III) appear to express SP during development (Gutierrez-Mecinas et al 2017) and may have been included among those that were ablated in this study.…”

Section: Understanding Cutaneous Mechanical Allodynia Circuitry: Pitfmentioning

confidence: 99%

Recent advances in our understanding of the organization of dorsal horn neuron populations and their contribution to cutaneous mechanical allodynia

2020

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The dorsal horns of the spinal cord and the trigeminal nuclei in the brainstem contain neuron populations that are critical to process sensory information. Neurons in these areas are highly heterogeneous in their morphology, molecular phenotype and intrinsic properties, making it difficult to identify functionally distinct cell populations, and to determine how these are engaged in pathophysiological conditions. There is a growing consensus concerning the classification of neuron populations, based on transcriptomic and transductomic analyses of the dorsal horn. These approaches have led to the discovery of several molecularly defined cell types that have been implicated in cutaneous mechanical allodynia, a highly prevalent and difficult-to-treat symptom of chronic pain, in which touch becomes painful. The main objective of this review is to provide a contemporary view of dorsal horn neuronal populations, and describe recent advances in our understanding of on how they participate in cutaneous mechanical allodynia.

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“…Moreover, immunohistochemical analyses demonstrated that the increase in both ipsilateral and contralateral D‐serine expression occurred predominantly in the SDH region (laminae I and II) of the spinal cord dorsal horn. This region is a significant site of pain transmission and modulation and receives nociceptive input from skin, muscle and visceral organs and thus is important in the initial processing of nociceptive information (Gutierrez‐Mecinas et al, ). Thus, the early increase in D‐serine in ipsilateral SDH and followed by a delayed increase in contralateral SDH suggests that the earlier increase in the ipsilateral SDH contributes to the initial development of ipsilateral mechanical allodynia, while the later increase in the contralateral SDH is associated with the delayed development of contralateral mechanical allodynia.…”

Section: Discussionmentioning

confidence: 99%

Differential involvement of ipsilateral and contralateral spinal cord astrocyte D‐serine in carrageenan‐induced mirror‐image pain: role of σ1 receptors and astrocyte gap junctions

Choi

Roh

Yoon

et al. 2018

British J Pharmacology

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Preprotachykinin A is expressed by a distinct population of excitatory neurons in the mouse superficial spinal dorsal horn including cells that respond to noxious and pruritic stimuli

Abstract: Expression of the substance P precursor preprotachykinin A defines a distinct population of superficial dorsal horn excitatory neurons, many of which respond to noxious or pruritic stimuli.

Cited by 59 publications

References 98 publications

Expression of cholecystokinin by neurons in mouse spinal dorsal horn

Expression of cholecystokinin by neurons in mouse spinal dorsal horn

Recent advances in our understanding of the organization of dorsal horn neuron populations and their contribution to cutaneous mechanical allodynia

Differential involvement of ipsilateral and contralateral spinal cord astrocyte D‐serine in carrageenan‐induced mirror‐image pain: role of σ1 receptors and astrocyte gap junctions

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