Cathepsin S in the spinal microglia contributes to remifentanil-induced hyperalgesia in rats

Ye, L; Xiao, Li; Yang, Shicong; Duan, Jingjing; Chen, Y; Chen, Yu

doi:10.1016/j.neuroscience.2016.12.030

Cited by 19 publications

(12 citation statements)

References 66 publications

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“…Considering that BA ameliorates not only visceral pain in mice [14] but also RIH in rats through its anti-oxidative and anti-inflammatory properties, it is promising to treat pain using BA. Consistent with our previous study and other reports, we found that RIH was initiated from 2 h and it peaked at 24 h after surgery and intraoperative remifentanil treatment [4,5,7,16]. Therefore, we determined the oxidative stress and inflammation in spinal dorsal horn 24 h after surgery to explore the underlying mechanisms by which BA alleviated RIH.…”

Section: Discussionsupporting

confidence: 83%

“…Increasing clinical and experimental evidence has revealed that intraoperative infusion of remifentanil induced acute postoperative hyperalgesia (RIH) [25,26]. Recently, the role of ROS and inflammation in RIH has gained much attention and reducing spinal oxidative stress RIH effectively alleviated in rats [5][6][7]27]. BA, a plant-derived pentacyclic triterpene, potently reduces visceral pain accompanied by reducing lipid peroxidation and MMP-9, and activating SOD [14].…”

Section: Discussionmentioning

confidence: 99%

“…Al-Pharmacology 2018;102:300-306 DOI: 10.1159/000493144 though the activation of spinal N-methyl-D-aspartate (NMDA) receptor pathway is well known to play a key role in RIH, it is not feasible to attenuate RIH by inhibiting NMDA receptors owing to the inevitable side effects (e.g., psychogenia) [2][3][4]. Recently, the overproduction of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) by remifentanil is reported to directly activate neuronal NMDA receptors and matrix metalloproteinase-9 (MMP-9) and facilitate RIH [5][6][7]. Acute morphine induces a significant up-regulation of MMP-9 in dorsal root ganglion (DRG), mediating neuroinflammatory response and central hypersensitivity [8].…”

Section: Introductionmentioning

confidence: 99%

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Attenuation of Remifentanil-Induced Hyperalgesia by Betulinic Acid Associates with Inhibiting Oxidative Stress and Inflammation in Spinal Dorsal Horn

Mao

Shu

et al. 2018

Pharmacology

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Remifentanil-induced hyperalgesia (RIH) is known to be associated with oxidative stress and inflammation. Betulinic acid (BA) was reported to reduce visceral pain owing to its anti-oxidative and anti-inflammatory potential. Here, we explored whether BA can attenuate RIH through inhibiting oxidative stress and inflammation in spinal dorsal horn. Sprague-Dawley rats were randomly divided into 4 groups: Control, Incision, RIH, and RIH pre-treated with BA. After pretreated with BA (25 mg/kg, i.g.) for 7 days, rats were subcutaneously infused with remifentanil (40 μg/kg) for 30 min during right plantar incision surgery to induce RIH. The paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), spinal oxidative stress and inflammatory mediators were determined. Intraoperative remifentanil infusion induced postoperative hyperalgesia, as evidenced by the significant decrease in PWMT and PWTL (p < 0.01), and the significant increase in oxidative stress and inflammation evidenced by up-regulations of malondialdehyde, 3-nitrotyrosine, interleukin-1β and tumour necrosis factor-α (p < 0.01) in spinal dorsal horn and matrix metalloproteinase-9 (MMP-9) activity (p < 0.01) in dorsal root ganglion, as well as a decrease in manganese superoxide dismutase activity (p < 0.01) compared with control and incision groups. All these results mentioned above were markedly reversed by pre-treatment with BA (p < 0.01) compared with RIH group. These findings demonstrated that BA can effectively attenuate RIH, which associates with potentially inhibiting oxidative stress and subsequently down-regulating MMP-9-related pro-inflammatory cyokines in spinal dorsal horn.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Attenuation of Remifentanil-Induced Hyperalgesia by Betulinic Acid Associates with Inhibiting Oxidative Stress and Inflammation in Spinal Dorsal Horn

Mao

Shu

et al. 2018

Pharmacology

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“…These observations were based on the increased glia numbers or elevated expression of nuclear factors and protein kinases in these glial cells (95,(136)(137)(138). Similar indirect effects were reported for other opioids acting at MOP receptors, including remifentanil, fentanyl and buprenorphine (139)(140)(141). Agonists of DOP and KOP receptors have not been tested.…”

Section: Gliamentioning

confidence: 76%

“…Furthermore, except for Chang et al (141) who used postoperative pain model, all other studies exclusively tested naïve mice or rats. Additionally, opioids were used at unconventional ultra-low doses or high doses which exceeded the analgesic doses used in pathological pain models, they were sometimes injected repetitively every few minutes, and hyperalgesia was measured 12 h, 24 h or 4 days following the last dose, which indicates opioid withdrawal-induced hyperalgesia (95,105,(135)(136)(137)(138)(139)(140)(141)(142). Therefore, these effects can be viewed in the context of dependence rather than pain management, which is in line with clinical findings [reviewed by (134,145)].…”

Section: Gliamentioning

confidence: 99%

Opioid Receptors in Immune and Glial Cells—Implications for Pain Control

2020

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neurons can induce analgesia in animal models, but the most clinically relevant are MOP receptor agonists (e.g., morphine, fentanyl). Opioids can also affect the function of immune cells, and their actions in relation to immunosuppression and infections have been widely discussed. Here, we analyze the expression and the role of opioid receptors in peripheral immune cells and glia in the modulation of pain. All four opioid receptors have been identified at the mRNA and protein levels in immune cells (lymphocytes, granulocytes, monocytes, macrophages) in humans, rhesus monkeys, rats or mice. Activation of leukocyte MOP, DOP, and KOP receptors was recently reported to attenuate pain after nerve injury in mice. This involved intracellular Ca 2+ -regulated release of opioid peptides from immune cells, which subsequently activated MOP, DOP, and KOP receptors on peripheral neurons. There is no evidence of pain modulation by leukocyte NOP receptors. More good quality studies are needed to verify the presence of DOP, KOP, and NOP receptors in native glia. Although still questioned, MOP receptors might be expressed in brain or spinal cord microglia and astrocytes in humans, mice, and rats. Morphine acting at spinal cord microglia is often reported to induce hyperalgesia in rodents. However, most studies used animals without pathological pain and/or unconventional paradigms (e.g., high or ultra-low doses, pain assessment after abrupt discontinuation of chronic morphine treatment). Therefore, the opioid-induced hyperalgesia can be viewed in the context of dependence/withdrawal rather than pain management, in line with clinical reports. There is convincing evidence of analgesic effects mediated by immune cell-derived opioid peptides in animal models and in humans. Together, MOP, DOP, and KOP receptors, and opioid peptides in immune cells can ameliorate pathological pain. The relevance of NOP receptors and N/OFQ in leukocytes, and of all opioid receptors, opioid peptides and N/OFQ in native glia for pain control is yet to be clarified.

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How omics is revealing new roles for glia in addiction

Bergkamp,

Neumaier

2024

Glia

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Experiments to study the biology of addiction have historically focused on the mechanisms through which drugs of abuse drive changes in the functioning of neurons and neural circuits. Glia have often been ignored in these studies, however, and this has left many questions in the field unanswered, particularly, surrounding how glia contribute to changes in synaptic plasticity, regulation of neuroinflammation, and functioning of neural ensembles given massive changes in signaling across the CNS. Omics methods (transcriptomics, translatomics, epigenomics, proteomics, metabolomics, and others) have expanded researchers' abilities to generate hypotheses and carry out mechanistic studies of glial cells during acquisition of drug taking, intoxication, withdrawal, and relapse to drug seeking. Here, we present a survey of how omics technological advances are revising our understanding of astrocytes, microglia, oligodendrocytes, and ependymal cells in addiction biology.

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Cathepsin S in the spinal microglia contributes to remifentanil-induced hyperalgesia in rats

Cited by 19 publications

References 66 publications

Attenuation of Remifentanil-Induced Hyperalgesia by Betulinic Acid Associates with Inhibiting Oxidative Stress and Inflammation in Spinal Dorsal Horn

Attenuation of Remifentanil-Induced Hyperalgesia by Betulinic Acid Associates with Inhibiting Oxidative Stress and Inflammation in Spinal Dorsal Horn

Opioid Receptors in Immune and Glial Cells—Implications for Pain Control

How omics is revealing new roles for glia in addiction

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