Dynorphin neurotoxicity induced nitric oxide synthase expression in ventral horn cells of rat spinal cord

Hu, Wenhui; Lee, Fu-Chun; Wan, X. Steven; Chen, Youting; Jen, Min-Feng

doi:10.1016/0304-3940(95)12246-x

Cited by 14 publications

(4 citation statements)

References 18 publications

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“…After SCI, low dynorphin levels mediate analgesia via activation of KORs on neurons [ 64 ]. However, prolonged exposure to, or supraphysiological concentrations of, dynorphin is neurotoxic, inducing paraplegia in naive rats when administered intrathecally, increasing SCI dysfunction in rodents, and increasing symptoms of pain [ 12 , 27 , 49 , 65 – 68 ]. Dynorphin A, the endogenous ligand of KOR, is upregulated after nerve injury, in response to pain signaling.…”

Section: Discussionmentioning

confidence: 99%

Morphine-induced changes in the function of microglia and macrophages after acute spinal cord injury

et al. 2022

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Background Opioids are among the most effective and commonly prescribed analgesics for the treatment of acute pain after spinal cord injury (SCI). However, morphine administration in the early phase of SCI undermines locomotor recovery, increases cell death, and decreases overall health in a rodent contusion model. Based on our previous studies we hypothesize that morphine acts on classic opioid receptors to alter the immune response. Indeed, we found that a single dose of intrathecal morphine increases the expression of activated microglia and macrophages at the injury site. Whether similar effects of morphine would be seen with repeated intravenous administration, more closely simulating clinical treatment, is not known. Methods To address this, we used flow cytometry to examine changes in the temporal expression of microglia and macrophages after SCI and intravenous morphine. Next, we explored whether morphine changed the function of these cells through the engagement of cell-signaling pathways linked to neurotoxicity using Western blot analysis. Results Our flow cytometry studies showed that 3 consecutive days of morphine administration after an SCI significantly increased the number of microglia and macrophages around the lesion. Using Western blot analysis, we also found that repeated administration of morphine increases β-arrestin, ERK-1 and dynorphin (an endogenous kappa opioid receptor agonist) production by microglia and macrophages. Conclusions These results suggest that morphine administered immediately after an SCI changes the innate immune response by increasing the number of immune cells and altering neuropeptide synthesis by these cells.

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Section: Discussionmentioning

confidence: 99%

Morphine-induced changes in the function of microglia and macrophages after acute spinal cord injury

et al. 2022

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“…By analogy to c-Fos activation in various experimental paradigms (Murphy et al, 2004), Dyn A may be considered a marker of neuronal circuits affected by pain (Mika et al, 2011;Schwarzer, 2009), stress (Knoll and Carlezon, 2010), substance abuse (Wee and Koob, 2010), brain and spinal cord injury (Faden, 1990;Goody et al, 2003;Hauser et al, 2005;Headrick et al, 1995;Hu et al, 1996;McIntosh et al, 1994). In this context, the overall effects of the unilateral injury may be explained as involving two types of Dyn A neuronal networks.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, all sham surgeries except R-Sham at the 24-h time point resulted in elevation of Dyn A levels, which is consistent with a nociceptive response. Considering that in models of spinal cord and brain injury, endogenous dynorphins may contribute to secondary CNS injury (Behrmann et al, 1993;Faden et al, 1987;Faden, 1990;Goody et al, 2003;Hauser et al, 2005;Headrick et al, 1995;Hu et al, 1996;McIntosh et al, 1994;McIntosh et al, 1987;Vink et al, 1990), it was anticipated that Dyn A would be upregulated in the TBI animals and contribute to neural injury via positive feedback. However, the present findings do not support this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…General and j-receptor-selective opioid antagonists were reported to be beneficial in experimental models of spinal cord injury and TBI, suggesting that endogenous dynorphins contribute to secondary CNS injury (Behrmann et al, 1993;Faden et al, 1987;McIntosh et al, 1987;Vink et al, 1990). Furthermore, Dyn A, the most pathogenic dynorphin, may cause tissue injury and cell death, and may exacerbate the clinical severity of traumatic injury to the head or spinal cord (Faden, 1990(Faden, ,1996Goody et al, 2003;Hauser et al, 2005;Headrick et al, 1995;Hu et al, 1996;McIntosh et al, 1994;Woods et al, 2006). Dyn A-induced tissue injury may involve both opioid and non-opioid components (Adjan et al, 2007;Bakshi et al, 1992;Faden, 1990;Hauser et al, 2005;Long et al, 1994;Woods et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Lateralized response in dynorphin A peptide levels after traumatic brain injury

Yakovleva

Fitting

Hauser

et al. 2013

Journal of the Neurological Sciences

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Traumatic brain injury (TBI) induces a cascade of primary and secondary events resulting in impairment of neuronal networks that eventually determines clinical outcome. The dynorphins, endogenous opioid peptides, have been implicated in secondary injury and neurodegeneration in rodent and human brain. To gain insight into the role of dynorphins in the brain's response to trauma, we analyzed short-term (1-day) and long-term (7-day) changes in dynorphin A (Dyn A) levels in the frontal cortex, hippocampus, and striatum, induced by unilateral left-side or right-side cortical TBI in mice. The effects of TBI were significantly different from those of sham surgery (Sham), while the sham surgery also produced noticeable effects. Both sham and TBI induced short-term changes and long-term changes in all three regions. Two types of responses were generally observed. In the hippocampus, Dyn A levels were predominantly altered ipsilateral to the injury. In the striatum and frontal cortex, injury to the right (R) hemisphere affected Dyn A levels to a greater extent than that seen in the left (L) hemisphere. The R-TBI but not L-TBI produced Dyn A changes in the striatum and frontal cortex at 7 days after injury. Effects of the R-side injury were similar in the two hemispheres. In naive animals, Dyn A was symmetrically distributed between the two hemispheres. Thus, trauma may reveal a lateralization in the mechanism mediating the response of Dyn A-expressing neuronal networks in the brain. These networks may differentially mediate effects of left and right brain injury on lateralized brain functions.

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