Astrocytes contribute to pain gating in the spinal cord

Xu, Qian; Ford, Neil C.; He, Shaoqiu; Huang, Qian; Anderson, Michael J.; Chen, Zhiyong; Yang, Fei; Crawford, LaTasha K.; Caterina, Michael J.; Guan, Yun; Dong, Xinzhong

doi:10.1126/sciadv.abi6287

Cited by 59 publications

(47 citation statements)

References 66 publications

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“…It is increasingly recognized that glial cells, such as astrocytes and microglia, play important roles in the development, gating, and maintenance of chronic pain (Gao & Ji, 2010;Xu et al, 2021). It has been…”

Section: Cb 1 R Expression In Glial Cells In the Lumbar Spinal Cordmentioning

confidence: 99%

Sex‐specific characteristics of cells expressing the cannabinoid 1 receptor in the dorsal horn of the lumbar spinal cord

Zhang

Zhou

et al. 2022

J of Comparative Neurology

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It is becoming increasingly clear that robust sex differences exist in the processing of acute and chronic pain in both rodents and humans. However, the underlying mechanism has not been well characterized. The dorsal horn of the lumbar spinal cord is the fundamental building block of ascending and descending pain pathways. It has been shown that numerous neurotransmitter and neuromodulator systems in the spinal cord, including the endocannabinoid system and its main receptor, the cannabinoid 1 receptor (CB 1 R), play vital roles in processing nociceptive information. Our previous findings have shown that CB 1 R mRNA is widely expressed in the brain in sex-dependent patterns. However, the sex-, lamina-, and cell-type-specific characteristics of CB 1 R expression in the spinal cord have not been fully described. In this study, the CB 1 R-iCre-EGFP mouse strain was generated to label and identify CB 1 R-positive (CB 1 R GFP ) cells. We reported no sex difference in CB 1 R expression in the lumbar dorsal horn of the spinal cord, but a dynamic distribution within superficial laminae II and III in female mice between estrus and nonestrus phases. Furthermore, the cell-type-specific CB 1 R expression pattern in the dorsal horn was similar in both sexes. Over 50% of CB 1 R GFP cells were GABAergic neurons, and approximately 25% were glycinergic and 20-30% were glutamatergic neurons. The CB 1 R-expressing cells also represented a subset of spinal projection neurons. Overall, our work indicates a highly consistent distribution pattern of CB 1 R GFP cells in the dorsal horn of lumbar spinal cord in males and females.

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Section: Cb 1 R Expression In Glial Cells In the Lumbar Spinal Cordmentioning

confidence: 99%

Sex‐specific characteristics of cells expressing the cannabinoid 1 receptor in the dorsal horn of the lumbar spinal cord

Zhang

Zhou

et al. 2022

J of Comparative Neurology

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“…To demonstrate the feasibility of high-speed, trans-segmental measurements with our wearable macroscopes, we performed imaging in awake GFAP-GCaMP6f mice (N=4) with constitutive green-fluorescent calcium indicator GCaMP6f expression in astrocytes. Dorsal horn astrocytes can exhibit noxious stimulus-evoked activity across large tissue regions (>500 μm rostrocaudal extent, limited by FOV) 10,11 , and this activity has been suggested to serve pain modulatory functions [11][12][13] . However, its spatial extent and temporal dynamics across spinal segments remain unknown.…”

Section: High-speed Trans-segmental Imaging Of Sensory-evoked Calcium Activity In Behavingmentioning

confidence: 99%

“…These technical limitations hamper our ability to decipher how broadly dispersed cellular networks contribute to somatosensory processing in behaving animals. Of particular interest, astrocytes are emerging as essential regulators of pain signaling in the spinal dorsal horn [10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Trans-segmental imaging in the spinal cord of behaving mice

Shekhtmeyster

Duarte

Carey

et al. 2021

Preprint

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Spinal cord circuits play crucial roles in transmitting and gating cutaneous somatosensory modalities, such as pain, but the underlying activity patterns within and across spinal segments in behaving mice have remained elusive. To enable such measurements, we developed a wearable widefield macroscope with a 7.9 mm2 field of view, subcellular lateral resolution, 2.7 mm working distance, and <10 g overall weight. We show that highly localized painful mechanical stimuli evoke widespread, coordinated astrocyte excitation across multiple spinal segments.

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“…Electrophysiology approaches are valuable for probing neuronal activity, but recordings in behaving animals from genetically defined cells across spinal laminae remain to be demonstrated. Emerging evidence also suggests that spinal astrocytes respond to different kinds of neural activity with calcium excitation and modulate pain signaling and motor function [4][5][6][7][8] . Astrocyte activity remains difficult to interrogate with the methods mentioned above.…”

Section: Introductionmentioning

confidence: 99%

Multiplex, translaminar imaging in the spinal cord of behaving mice

Shekhtmeyster

Carey

Duarte

et al. 2021

Preprint

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While the spinal cord is known to play critical roles in sensorimotor processing, including pain-related signaling, corresponding activity patterns in genetically defined cell types across spinal laminae have remained elusive. Calcium imaging has enabled cellular activity measurements in behaving rodents but is currently limited to superficial regions. Using chronically implanted microprisms, we imaged sensory and motor evoked activity in regions and at speeds inaccessible by other high-resolution imaging techniques. To enable translaminar imaging in freely behaving animals through implanted microprisms, we additionally developed wearable microscopes with custom-compound microlenses. This new integrated system addresses multiple challenges of previous wearable microscopes, including their limited working distance, resolution, contrast, and achromatic range. The combination of these innovations allowed us to uncover that dorsal horn astrocytes in behaving mice show somatosensory program-dependent and lamina-specific calcium excitation. Additionally, we show that tachykinin precursor 1 (Tac1)-expressing neurons exhibit upper laminae-restricted activity to acute mechanical pain but not locomotion.

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Astrocytes contribute to pain gating in the spinal cord

Abstract: Spinal cord astrocytes represent an important component of pain gating and exert nonneuronal control of pain.

Cited by 59 publications

References 66 publications

Sex‐specific characteristics of cells expressing the cannabinoid 1 receptor in the dorsal horn of the lumbar spinal cord

Sex‐specific characteristics of cells expressing the cannabinoid 1 receptor in the dorsal horn of the lumbar spinal cord

Trans-segmental imaging in the spinal cord of behaving mice

Multiplex, translaminar imaging in the spinal cord of behaving mice

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