Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin–saporin

Cao, Fei; Chen, Shasha; Yan, Xiao-Feng; Xiao, Xiongxin; Liu, Xijiang; Yang, Shaobing; Xu, Aiguo; Gao, Feng; Yang, Hui; Chen, Zhijun; Tian, Yuan

doi:10.1016/j.neuro.2009.06.004

Cited by 13 publications

(11 citation statements)

References 48 publications

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“…Collectively, the current and previous results suggest that minocycline inhibits NF-κB activation. [7] and activates astrocytes that release pro-inflammatory cytokines in the spinal cord to enhance and prolong a persistent pain state [36,60,61] . It is reasonable to argue that a complex neuroinflammatory mechanism is involved in BCP.…”

Section: Minocycline Attenuates Bcp Via Nf-κb Inhibitionmentioning

confidence: 99%

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

et al. 2016

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Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats.Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

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Section: Minocycline Attenuates Bcp Via Nf-κb Inhibitionmentioning

confidence: 99%

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

et al. 2016

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“…3,36 However, baseline nociceptive thresholds remain unchanged after derm-sap treatment, indicating a more prominent role for the RVM in state-dependent pain modulation. 7,34 The effect of derm-sap on the function of RVM neurons involved in producing antinociception has received less attention. In this study, we found that RVM neurons and circuitry necessary for the production of analgesia remained largely intact and functional after microinjections of derm-sap.…”

Section: Discussionmentioning

confidence: 99%

“…14,15,18,19,23 The microinjection of the neurotoxin dermorphin–saporin (derm-sap) has been used to selectively ablate MOR-expressing neurons in the RVM, demonstrated by in situ hybridization for MOR mRNA and immunohistochemistry for MOR protein. 3,7,34,36 Additional studies have determined that MOR-expressing neurons in the RVM, presumably the on-cells, contribute to behavioral hyperalgesia produced by nerve injury, pancreatitis, intracolonic mustard oil, and chronic stress. 3,34–36,39,40 Although it has been hypothesized that ablation of MOR-expressing neurons in the RVM selectively reduces the number of on-cells, this idea has not been directly tested.…”

Section: Introductionmentioning

confidence: 99%

Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons

Harasawa

Johansen

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et al. 2016

Pain

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The rostral ventromedial medulla (RVM) exerts both inhibitory and excitatory controls over nociceptive neurons in the spinal cord and medullary dorsal horn. Selective ablation of mu-opioid receptor (MOR)-expressing neurons in the RVM using saporin conjugated to the MOR agonist dermorphin–saporin (derm-sap) attenuates stress and injury–induced behavioral hypersensitivity, yet the effect of RVM derm-sap on the functional integrity of the descending inhibitory system and the properties of RVM neurons remain unknown. Three classes of RVM neurons (on-cells, off-cells, and neutral cells) have been described with distinct responses to noxious stimuli and MOR agonists. Using single unit recording in lightly anesthetized rats, RVM neurons were characterized after microinjections of derm-sap or saporin. Derm-sap treatment resulted in a reduction in on-cells and off-cells when compared to saporin controls (P < 0.05). The number of neutral cells remained unchanged. After derm-sap treatment, RVM microinjections of the glutamate receptor agonist homocysteic acid increased tail-flick latencies, whereas the MOR agonist DAMGO had no effect. Furthermore, electrical stimulation of the periaqueductal gray produced analgesia in both derm-sap and saporin controls with similar thresholds. Microinjection of kynurenic acid, a glutamate receptor antagonist, into the RVM disrupted periaqueductal gray stimulation–produced analgesia in both saporin-treated and derm-sap– treated rats. These results indicate that MOR-expressing neurons in the RVM are not required for analgesia produced by either direct or indirect activation of neurons in the RVM.

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“…Animals were allowed to recover for a minimum of 14-days post-surgery before beginning behavioral testing. This time-point was chosen based on preliminary studies indicating loss of RVM MOR-induced antinociception at this time-point following intra-RVM injections of Derm-sap, and an additional study that demonstrated a recovery of acute cardiovascular and microglial effects produced by RVM injections of Derm-sap by day 14 (Cao et al, 2009).…”

Section: Surgical Proceduresmentioning

confidence: 99%

“…Hind paw mechanical hypersensitivity was induced by repeated application of a von Frey filament to the whisker pad region of rats, and selective ablation of MOR-expressing neurons was accomplished via microinjection of the neurotoxin dermorphin-saporin into the RVM (Bee and Dickenson, 2008;Burgess et al, 2002;Cao et al, 2009;Gardell et al, 2003;Porreca et al, 2001;Vera-Portocarrero et al, 2006a, 2006b.…”

Section: Introductionmentioning

confidence: 99%

Selective ablation of mu-opioid receptor expressing neurons in the rostral ventromedial medulla attenuates stress-induced mechanical hypersensitivity

2011

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Evaluation of side effects through selective ablation of the mu opioid receptor expressing descending nociceptive facilitatory neurons in the rostral ventromedial medulla with dermorphin–saporin

Cited by 13 publications

References 48 publications

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons

Selective ablation of mu-opioid receptor expressing neurons in the rostral ventromedial medulla attenuates stress-induced mechanical hypersensitivity

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