Intra-CA1 Administration of Minocycline Alters the Expression of Inflammation-Related Genes in Hippocampus of CCI Rats

He, Li; Xu, Rui; Chen, Yuan-Shou; Liu, Xiaohong; Pan, You Fu; Cao, Song; Xu, Tao; Tian, Hong; Zeng, Junwei

doi:10.3389/fnmol.2019.00248

Cited by 15 publications

(9 citation statements)

References 63 publications

(71 reference statements)

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“…We also report a plenty of microglial activation in CA1, CA3, and DG regions of hippocampus of cancer bearing mice and this effect was alleviated by MHC-I knockdown. This also accords with the earlier observations, which showed that microglial activation in the hippocampus are associated with chronic constriction injury induced hyperalgesia (He et al 2019) and intracerebroventricular application of minocycline in hippocampus alleviates depressive-like behaviors in BCP rats by inhibiting microglia activation (Dai et al 2019). We speculate that the upregulation of MHC-I accompanied by the microglial activation during BCP induces a reorganization of the circuit within the hippocampus that mediates the development of sensory pain and emotional behaviors.…”

Section: Discussionsupporting

confidence: 92%

Major Histocompatibility Complex Class I in Hippocampus Promotes the Comorbid Depressive Symptoms in Cancer Induced Bone Pain via Regulating the Microglial TREM2/DAP12 Signaling

Li¹,

Jia²,

Xiong³

et al. 2021

Preprint

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Pain and depression comorbidity affect the patients’ both physical and mental health and quality of life seriously. The comorbid depressive symptoms in cancer pain severely affect the recognition and treatment of pain. Similarly, cancer pain patients with depression are inclined toward more despair and greater impairment. The mechanisms responsible for the comorbid depressive symptoms in cancer induced bone pain have not been fully delineated and the currently available therapeutics for this pathological pain is relatively limited. In the present study, we observed that carcinoma cells implantation induced pain and depression comorbidity resulted in the upregulation of major histocompatibility complex class I (MHC-I) in hippocampus associated with the activation of TREM2/DAP12-mediated microglial signaling pathways. These observations were reversed by a lentiviral vector harboring RNA interference sequence targeting MHC-I injected into the hippocampus of tumor bearing mice. Together, these results suggest that MHC-I involves in the cancer induced bone pain and depression comorbidity through regulating the TREM2/DAP12-mediated signals in microglia of hippocampus. Suppression of MHC-I could be a therapeutic target for cancer induced bone pain.

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Section: Discussionsupporting

confidence: 92%

Major Histocompatibility Complex Class I in Hippocampus Promotes the Comorbid Depressive Symptoms in Cancer Induced Bone Pain via Regulating the Microglial TREM2/DAP12 Signaling

Li¹,

Jia²,

Xiong³

et al. 2021

Preprint

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“…Therefore, based on our studies conducted at this time point, it appears that cenicriviroc mainly benefited the activation of microglia/macrophages. Previous studies, including ours, have shown that minocycline, which acts as an inhibitor of microglia/macrophages, reduced hypersensitivity 7 days after nerve damage by lowering the level of pronociceptive factors, such as IL-1beta, IL-6, and IL-18 (46)(47)(48)(49)(50). Our previous results have also demonstrated that preemptive and repeated intrathecal injections of a selective CCR2 (RS504393) and CCR5 (maraviroc) antagonist attenuate neuropathic pain due to the inhibition of activation of IBA-1-positive cells (11,14).…”

Section: Discussionmentioning

confidence: 91%

Bidirectional Action of Cenicriviroc, a CCR2/CCR5 Antagonist, Results in Alleviation of Pain-Related Behaviors and Potentiation of Opioid Analgesia in Rats With Peripheral Neuropathy

et al. 2020

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Clinical management of neuropathic pain is unsatisfactory, mainly due to its resistance to the effects of available analgesics, including opioids. Converging evidence indicates the functional interactions between chemokine and opioid receptors and their influence on nociceptive processes. Recent studies highlight that the CC chemokine receptors type 2 (CCR2) and 5 (CCR5) seem to be of particular interest. Therefore, in this study, we investigated the effects of the dual CCR2/CCR5 antagonist, cenicriviroc, on pain-related behaviors, neuroimmune processes, and the efficacy of opioids in rats after chronic constriction injury (CCI) of the sciatic nerve. To define the mechanisms of action of cenicriviroc, we studied changes in the activation/influx of glial and immune cells and, simultaneously, the expression level of CCR2, CCR5, and important pronociceptive cytokines in the spinal cord and dorsal root ganglia (DRG). We demonstrated that repeated intrathecal injections of cenicriviroc, in a dose-dependent manner, alleviated hypersensitivity to mechanical and thermal stimuli in rats after sciatic nerve injury, as measured by von Frey and cold plate tests. Behavioral effects were associated with the beneficial impact of cenicriviroc on the activation/influx level of C1q/IBA-1-positive cells in the spinal cord and/or DRG and GFAP-positive cells in DRG. In parallel, administration of cenicriviroc decreased the expression of CCR2 in the spinal cord and CCR5 in DRG. Concomitantly, we observed that the level of important pronociceptive factors (e.g., IL-1beta, IL-6, IL-18, and CCL3) were increased in the lumbar spinal cord and/or DRG 7 days following injury, and cenicriviroc was able to prevent these changes. Additionally, repeated administration of this dual CCR2/CCR5 antagonist enhanced the analgesic effects of morphine and buprenorphine in neuropathic rats, which can be associated with the ability of cenicriviroc to prevent nerve injury-induced downregulation of all opioid receptors at the DRG level. Overall, our results suggest that pharmacological modulation based on the simultaneous blockade of CCR2 and CCR5 may serve as an innovative strategy for the treatment of neuropathic pain, as well as in combination with opioids.

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“…Each rat's left hind paw was stimulated three times at 5 min intervals during the formal examination. Paw withdrawal, flinching, or licking was regarded as positive behavior ( 29 ). Each value was recorded; MWT were represented by the mean values.…”

Section: Methodsmentioning

confidence: 99%

Brain Functional Alteration at Different Stages of Neuropathic Pain With Allodynia and Emotional Disorders

et al. 2022

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Intra-CA1 Administration of Minocycline Alters the Expression of Inflammation-Related Genes in Hippocampus of CCI Rats

Cited by 15 publications

References 63 publications

Major Histocompatibility Complex Class I in Hippocampus Promotes the Comorbid Depressive Symptoms in Cancer Induced Bone Pain via Regulating the Microglial TREM2/DAP12 Signaling

Major Histocompatibility Complex Class I in Hippocampus Promotes the Comorbid Depressive Symptoms in Cancer Induced Bone Pain via Regulating the Microglial TREM2/DAP12 Signaling

Bidirectional Action of Cenicriviroc, a CCR2/CCR5 Antagonist, Results in Alleviation of Pain-Related Behaviors and Potentiation of Opioid Analgesia in Rats With Peripheral Neuropathy

Brain Functional Alteration at Different Stages of Neuropathic Pain With Allodynia and Emotional Disorders

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