Activation of Extracellular Signal-Regulated Kinase1/2 in the Medial Prefrontal Cortex Contributes to Stress-Induced Hyperalgesia

Qi, Jian; Chen, Chen; Lu, Ya-Cheng; Zhang, Ting; Xu, Hao; Cui, Yuanyuan; Chen, Yan-Zhou; Wang, Wen; Dong, Yu-Lin; Li, Yunqing

doi:10.1007/s12035-014-8707-8

Cited by 17 publications

(19 citation statements)

References 36 publications

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“…PWT was further reduced in injured hindpaws of the SPS + CFA-exposed rats from day 9 after CFA injection compared to CFA-exposed rats (P < 0.05)7. In the present study, there was a significant effect (A, F 2,105 = 95.72, P < 0.001; B, F 3,140 = 84.33, P < 0.001) on the paw withdrawal thresholds (PWTs).…”

Section: Resultssupporting

confidence: 41%

“…Previous studies conducted by our research group have demonstrated that exposure to PTSD can enhance CFA-induced allodynia7. Both CFA- and SPS + CFA-treated animals demonstrated mechanical hyperalgesia compared to the control group.…”

Section: Discussionmentioning

confidence: 62%

“…1). A detailed procedure can be found in our previously published study7. For c- fos ASO administration, the rats were randomly assigned to one of three groups: (1) ASO group: rats underwent c- fos ASO (5′-GAA CAT CATGGTCGT-3′) intrathecal administration (dissolved in 5% DMSO, 5 μg/10 μl); (2) SO group: rats underwent c- fos sense oligodeoxynucleotide (SO, 5′-ACG ACC ATG ATG TTC-3′) intrathecal administration (dissolved in 5% DMSO, 5 μg/10 μl); (3) DMSO group: rats underwent DMSO (5% DMSO, 10 μl) intrathecal administration.…”

Section: Methodsmentioning

confidence: 99%

“…Clinical observations suggest stressful stimuli promote an increase in pain sensitivity, leading to the exacerbation of existing pain45. These phenomena are collectively termed stress-induced hyperalgesia (SIH)67. Understanding how stress affects the development and severity of pain provides a potential application for therapies in a variety of pain syndromes.…”

mentioning

confidence: 99%

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Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

Chen

Meng

et al. 2016

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Stress has been shown to enhance pain sensitivity resulting in stress-induced hyperalgesia. However, the underlying mechanisms have yet to be elucidated. Using single-prolonged stress combined with Complete Freund’s Adjuvant injection model, we explored the reciprocal regulatory relationship between neurons and microglia, which is critical for the maintenance of posttraumatic stress disorder (PTSD)-induced hyperalgesia. In our assay, significant mechanical allodynia was observed. Additionally, activated neurons in spinal dorsal horn were observed by analysis of Fos expression. And, microglia were also significantly activated with the presence of increased Iba-1 expression. Intrathecal administration of c-fos antisense oligodeoxynucleotides (ASO) or minocycline (a specific microglia inhibitor) attenuated mechanical allodynia. Moreover, intrathecal administration of c-fos ASO significantly suppressed the activation of neurons and microglia. Interestingly, inhibition of microglia activation by minocycline significantly suppressed the activation of both neurons and microglia in spinal dorsal horn. P38 inhibitor SB203580 suppressed IL-6 production, and inhibition of IL-6 receptor (IL-6R) activation by tocilizumab suppressed Fos expression. Together, our data suggest that the presence of a “crosstalk” between activated microglia and neurons in the spinal dorsal horn, which might contribute to the stress-induced hyperactivated state, leading to an increased pain sensitivity.

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Section: Resultssupporting

confidence: 41%

Section: Discussionmentioning

confidence: 62%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

Chen

Meng

et al. 2016

Sci Rep

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“…Many studies have shown the positive correlation between preoperative anxiety and postoperative pain intensity as well as analgesic consumption [5][6][7][8][9]. The phenomenon that exposure to physical or psychological stressors can enhance nociception and pain sensitivity is described as stress-induced hyperalgesia (SIH) [10][11][12][13][14][15][16]. Although more and more attention has been paid to investigate this phenomenon, the potential underlying molecular mechanism has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia

et al. 2016

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Clinically, preoperative anxiety adversely affected postoperative hyperalgesia. As stress-induced glucocorticoids (GCs) were reported to sensitize the activation of microglia, the present study investigated whether and how GCs and microglia played in the process of preoperative anxiety-induced postoperative hyperalgesia. The study used an animal model that exposed rats to single prolonged stress (SPS) procedure to induce preoperative anxiety-like behaviors 24 h before the plantar incisional surgery. Behavioral testing revealed that preoperative SPS enhanced the mechanical allodynia induced by plantar incision. SPS was also found to induce elevated circulating corticosterone levels, potentiate the activation of spinal microglia, and increase the expression of spinal proinflammatory cytokines. Inhibition of microglia by pretreatment with minocycline attenuated the SPS-enhanced mechanical allodynia, and this was accompanied by decreased activation of spinal microglia and expression of proinflammatory cytokines. Another experiment was conducted by administering RU486, the GC receptor (GR) antagonist, to rats. The results showed that RU486 suppressed SPS-induced and SPS-potentiated proinflammatory activation of spinal microglia and revealed analgesic effects. Together, these data indicated that inhibition of stress-induced GR activation attenuated the preoperative anxiety-induced exacerbation of postoperative pain, and the suppression of spinal microglia activation may underlie this anti-hyperalgesia effect. Pending further studies, these findings suggested that GR and spinal microglia may play important roles in the development of preoperative anxiety-induced postoperative hyperalgesia and may serve as novel targets to prevent this phenomenon.

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Effects of Post-Weaning Chronic Stress on Nociception, Spinal Cord μ-Opioid, and α2-Adrenergic Receptors Expression in Rats and Their Offspring

et al. 2018

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Stressful situations can change biological process in human and animal, and some of these changes may transfer to the next generations. We used a communication box to induce chronic electrical foot-shock stress in rats. Tail flick latency and formalin test were done to determine the level of pain sensation. Real-time RT-PCR was used to measure the level of spinal cord μ-opioid (MOR) and α2-adrenergic receptors (α2-AR) mRNA. We demonstrate that chronic stress can change nociception and leads to hyperalgesia. Moreover, spinal cord MOR mRNA level decreased following chronic stress. We did not observe any significant changes in the level of spinal cord α2-AR mRNA between stressed and non-stressed rats. In addition, non-stressed sons of stressed mothers showed hyperalgesia compared to the control group. They showed lesser level of MOR mRNA level in comparison to the control rats. Furthermore, stressed sons of stressed mothers illustrated more hyperalgesia than the other stressed groups. We indicate that chronic stress can reduce spinal cord MOR mRNA level and lead to hyperalgesia. Additionally, these changes can transfer to offspring.

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Activation of Extracellular Signal-Regulated Kinase1/2 in the Medial Prefrontal Cortex Contributes to Stress-Induced Hyperalgesia

Cited by 17 publications

References 36 publications

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

Crosstalk between Activated Microglia and Neurons in the Spinal Dorsal Horn Contributes to Stress-induced Hyperalgesia

Glucocorticoid-Potentiated Spinal Microglia Activation Contributes to Preoperative Anxiety-Induced Postoperative Hyperalgesia

Effects of Post-Weaning Chronic Stress on Nociception, Spinal Cord μ-Opioid, and α2-Adrenergic Receptors Expression in Rats and Their Offspring

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