Abstract | BACKGROUND: Increasing evidence suggests that patients with eating disorders are more likely to develop chronic pain. A misaligned diet has been reported to disrupt the sleep-awake rhythms. Combined with our previous investigation on circadian pain, we aimed to investigate the role of misaligned diet in the pain sensitivity and the underlying mechanisms. METHODS: Two-month-old C57BL/6J male mice were administered chronic constriction injury (CCI) surgery to establish neuropathic pain models. CCI mice were randomized to scheduled food access throughout the whole day (CCI-free), during the daytime (CCI-misaligned), and at night (CCI-aligned), respectively. The paw withdrawal mechanical threshold, indicating pain behavior, was measured by Von Frey. The gross motor activity pattern indicating the sleep-awake rhythm was monitored by Mini-Mitter. Melatonin (Mel) was administered to ameliorate the sleep-awake rhythm (CCI-free + Mel and CCI-misaligned + Mel). The expressions of circadian pain-related proteins were detected by quantitative polymerase chain reaction and western blot. The primary outcome is the pain threshold and the secondary outcome is the sleep-awake rhythm. RESULTS: Misaligned diet during the peri-CCI surgery period significantly decreased the paw withdrawal mechanical threshold compared with the CCI-free mice (day 14: 0.40 ± 0.09 vs 0.64 ± 0.15; P = .03;) and altered the sleep-awake rhythm. Mel pretreatment alleviated the increased pain (day 14, CCI-misaligned + Mel versus CCI-misaligned: day 14: 0.60 ± 0.13 vs 0.35 ± 0.12; P = .022) and the disrupted sleep-awake rhythm caused by misaligned feeding. The mRNA levels of N-methyl-D-aspartate receptor subtype 2B (NR2B), Ca/ calmodulin-dependent protein kinase II ( CaMKII), and cyclic adenosine monophosphate-response element binding protein (CREB) in the spinal dorsal horn increased in CCI-misaligned mice compared with the CCI-free mice. The phosphor-NR2B, phosphor- CaMKII, and phosphor-CREB also increased in CCI-misaligned mice compared with the CCI-free mice. However, the expressions of NR2B, CaMKII, and CREB were decreased in CCI-misaligned + Mel mice compared to CCI-misaligned mice at both transcriptional and translational levels. CONCLUSIONS: Misaligned diet might aggravate pain sensitivity through the disruption of the sleep-awake cycle, which could be recovered by Mel. NR2B-CaMKII-CREB may participate in the disruption of sleep-awake rhythm-mediated pain aggravation.
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Authors | Fangxia Xu, Xin Zhao, Huan Liu, Xueming Shao, Shuaishuai Chu, Xiangdan Gong, Zhengliang Ma, Xiaoping Gu |
Journal | Anesthesia and analgesia
(Anesth Analg)
Vol. 127
Issue 1
Pg. 255-262
(07 2018)
ISSN: 1526-7598 [Electronic] United States |
PMID | 29261550
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Creb1 protein, mouse
- Cyclic AMP Response Element-Binding Protein
- NR2B NMDA receptor
- Receptors, N-Methyl-D-Aspartate
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
- Melatonin
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Topics |
- Activity Cycles
(drug effects)
- Animals
- Behavior, Animal
(drug effects)
- Calcium-Calmodulin-Dependent Protein Kinase Type 2
(genetics, metabolism)
- Cyclic AMP Response Element-Binding Protein
(genetics, metabolism)
- Disease Models, Animal
- Feeding Behavior
- Male
- Meals
- Melatonin
(pharmacology)
- Mice, Inbred C57BL
- Motor Activity
(drug effects)
- Neuralgia
(metabolism, physiopathology, prevention & control, psychology)
- Pain Perception
- Pain Threshold
- Phosphorylation
- Posterior Horn Cells
(metabolism)
- Receptors, N-Methyl-D-Aspartate
(genetics, metabolism)
- Sleep
(drug effects)
- Spinal Cord Dorsal Horn
(metabolism, physiopathology)
- Time Factors
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