Bradykinin Enhances AMPA and NMDA Receptor Activity in Spinal Cord Dorsal Horn Neurons by Activating Multiple Kinases to Produce Pain Hypersensitivity

Kohno, Tatsuro; Wang, Haibin; Amaya, Fumimasa; Brenner, Gary J.; Cheng, Jen-Kun; Ji, Ru-Rong; Woolf, Clifford J.

doi:10.1523/jneurosci.5349-07.2008

Cited by 101 publications

(100 citation statements)

References 45 publications

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“…PLA 2 initiates the release of arachidonic acid which is converted to PGE2, by cyclooxygenase (Cox) and prostaglandin synthases, and can activate PKA via E-prostanoid G-protein coupled receptors (Smith et al, 2000). PKA and PKC may phosphorylate NMDA or AMPA receptor subunits, changing the membrane traffic and their kinetic properties (voltage-dependent block, channel open time, burst behavior), triggering an increase in synaptic effectiveness (Kohno et al, 2008). Very recently, it was shown that B2R stimulation leads to neuroprotection after NMDA excitotoxicity in the CA1 area of rat hippocampal slices via phosphatidylinositol 3-kinase and not by MEK/MAPK signaling (Martins et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Kinin B2 receptor can play a neuroprotective role in Alzheimer's disease

Caetano¹,

Dong-Creste²,

Amaral³

et al. 2015

Neuropeptides

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Section: Discussionmentioning

confidence: 99%

Kinin B2 receptor can play a neuroprotective role in Alzheimer's disease

Caetano¹,

Dong-Creste²,

Amaral³

et al. 2015

Neuropeptides

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“…Once activated, ERK can regulate the phosphorylation of many membrane receptors and the expression of many genes, resulting in short- and long-term functional changes in the spinal nociception process [31,32]. For example, ERK activation has been demonstrated to regulate the expression of several pain-related genes including COX-2, neurokinin 1 and tyrosine receptor kinase B [33].…”

Section: Discussionmentioning

confidence: 99%

Osthole, a Coumadin Analog from <b><i>Cnidium monnieri</i></b> (L.) Cusson, Ameliorates Nucleus Pulposus-Induced Radicular Inflammatory Pain by Inhibiting the Activation of Extracellular Signal-Regulated Kinase in Rats

Wang

et al. 2017

Pharmacology

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Aim: This study was aimed at assessing the role of extracellular signal regulated kinase (ERK) in mechanical allodynia resulting from lumbar disc herniation (LDH) and exploring the osthole's anti-nociceptive effect on ERK activation. Methods: Radicular pain was generated by applying nucleus pulposus (NP) to the L₅ dorsal root ganglion (DRG). Allodynia was measured using Von Frey filaments to calculate the mechanical pain threshold. Phosphorylated ERK and total ERK protein in the lumbar spinal dorsal horn was detected by using the Western blot technique. Cyclooxygenase 2 (COX-2) mRNA was assessed by real-time reverse-transcription polymerase chain reaction. Results: The application of NP to L₅ DRG induced mechanical hypersensitivity which lasted for at least 28 days, and a significant increase of ERK phosphorylation in the ipsilateral spinal dorsal horn from postoperative day (POD) 1 to POD 21. ERK inhibitor attenuated NP-induced hyperalgesia compared to the dimethyl sulfoxide-(vehicle control) administered group (p < 0.05). Epidural treatment with osthole could ameliorate NP-evoked hyperalgesia by suppressing the activation of ERK rather than decreasing the expression of ERK protein. Osthole could also inhibit the increased expression of COX-2 mRNA in spinal dorsal horn, which was a known downstream effect of ERK signaling pathway. Conclusions: Our results suggest that ERK activation in the spinal dorsal horn plays a vital role in NP-evoked hyperalgesia. Osthole exerts analgesic effect on radicular inflammatory pain in LDH rat model, by down-regulating the mRNA expression of the target gene of COX-2 via inhibiting ERK activation in the spinal dorsal horn.

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“…In many pain models, PKC has been found to be necessary for maintaining central sensitization and directly affects molecular signaling pathways mediating central sensitization in pain. Activation of PKC results in the direct activation of intracellular signaling molecules of the mitogenactivated protein kinase (MAPK) family that are critically involved in pain sensitization, including extracellular-signal-related kinase (ERK) 1 and 2, p38, and stress-activated protein kinase (SAPK)/ c-Jun N-terminal kinase (JNK) [4,22,23]. In addition, PKC γ has also been reported to phosphorylate NMDA receptors [24] and promote the trafficking of NMDA receptors to the cell membrane [25].…”

Section: Discussionmentioning

confidence: 99%