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- Title
Ventrolateral Periaqueductal Gray Astrocytes Regulate Nociceptive Sensation and Emotional Motivation in Diabetic Neuropathic Pain.
- Authors
Lan Yang; Jingshan Lu; Jianpeng Guo; Jian Chen; Fangfang Xiong; Xinyao Wang; Li Chen; Changxi Yu
- Abstract
Diabetic neuropathic pain (DNP) is a diabetes complication experienced by many patients. Ventrolateral periaqueductal gray (vlPAG) neurons are essential mediators of the descending pain modulation system, yet the role of vlPAG astrocytes in DNP remains unclear. The present study applied a multidimensional approach to elucidate the role of these astrocytes in DNP. We verified the activation of astrocytes in different regions of the PAG in male DNP-model rats. We found that only astrocytes in the vlPAG exhibited increased growth. Furthermore, we described differences in vlPAG astrocyte activity at different time points during DNP progression. After the 14th day of modeling, vlPAG astrocytes exhibited obvious activation and morphologic changes. Furthermore, activation of Gq-designer receptors exclusively activated by a designer drug (Gq-DREADDs) in vlPAG astrocytes in naive male rats induced neuropathic pain-like symptoms and pain-related aversion, whereas activation of Gi-DREADDs in vlPAG astrocytes in male DNP-model rats alleviated sensations of pain and promoted pain-related preference behavior. Thus, bidirectional manipulation of vlPAG astrocytes revealed their potential to regulate pain. Surprisingly, activation of Gi-DREADDs in vlPAG astrocytes also mitigated anxiety-like behavior induced by DNP. Thus, our results provide direct support for the hypothesis that vlPAG astrocytes regulate diabetes-associated neuropathic pain and concomitant anxiety-like behavior.
- Subjects
NEURALGIA; ASTROCYTES; PAIN; DESIGNER drugs; DIABETES complications; SENSES
- Publication
Journal of Neuroscience, 2022, Vol 42, Issue 43, p8184
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.0920-22.2022