Intracisternal Administration of NR2 Subunit Antagonists Attenuates the Nociceptive Behavior and p-p38 MAPK Expression Produced by Compression of the Trigeminal Nerve Root

Jeon, Hye Jin; Han, Seung Ro; Lim, Koang H; Won, Kyoung A.; Bae, Yong Chul; Ahn, Dong Kuk

doi:10.1186/1744-8069-7-46

Cited by 22 publications

(22 citation statements)

References 51 publications

(78 reference statements)

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“…In the present study, the injection of NMDA or mGlu1 receptor antagonists into the DRt reduced formalin‐induced secondary allodynia and hyperalgesia. This evidence, along with other studies, supports the role of glutamate receptors in supraspinal modulation of inflammatory or neuropathic pain (Coutinho et al ., ; Urban & Gebhart, ; Varty et al ., ; Ansah et al ., ; Jeon et al ., ). Other studies have shown the importance of spinal mechanisms (Nozaki‐Taguchi & Yaksh, ; Pogatzki et al ., ) and the contribution of other supraspinal structures (i.e.…”

Section: Discussionmentioning

confidence: 97%

Role of glutamate receptors in the dorsal reticular nucleus in formalin‐induced secondary allodynia

Ambriz-Tututi

Palomero-Rivero

Ramírez-López

et al. 2013

Eur J of Neuroscience

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The role of glutamate receptors present in the medullary dorsal reticular nucleus (DRt) in the formalin test and formalin-induced secondary nociception was studied in rats. Secondary mechanical allodynia was assessed with von Frey filaments applied to the rat's hindpaw, and secondary thermal hyperalgesia was evaluated with the tail-immersion test. The selective glutamate receptor antagonists MK801 (N-methyl-D-aspartate receptor antagonist), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA/KA receptor antagonist) and A841720 (metabotropic glutamate 1 receptor antagonist) were injected into the DRt before or 6 days after formalin injection in the rat. In the formalin test, the three antagonists significantly reduced the number of flinches in both phases of the test. DRt microinjection of MK801 or A841720, but not of CNQX, reduced both secondary nociceptive behaviors. Moreover, pre-treatment with the three antagonists injected into the DRt prevented the development of secondary mechanical allodynia and secondary thermal hyperalgesia. Similarly, in these rats, the number of c-Fos-like immunoreactive neurons were markedly reduced in both the superficial and deep lamina of the dorsal horn. Our findings support the role of DRt as a pain facilitator in acute and chronic pain states, and suggest a key role of glutamate receptors during the development and maintenance of formalin-induced secondary allodynia.

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Section: Discussionmentioning

confidence: 97%

Role of glutamate receptors in the dorsal reticular nucleus in formalin‐induced secondary allodynia

Ambriz-Tututi

Palomero-Rivero

Ramírez-López

et al. 2013

Eur J of Neuroscience

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“…NMDA receptors are formed by several subunits, with the NMDA-NR2B subunits reported to contribute to the development of central sensitization and neuropathic pain 58 . Specifically, it has been reported that NR2B phosphorylation of dorsal horn neurons is enhanced in neuropathic 59 and post-inflammatory 60 pain models, and the use of NR2B antagonists has been shown to reduce inflammatory 61 , 62 , peripheral 61 , 63 and spinal cord injury-induced neuropathic pain 64 . Furthermore, σ 1 R activation has been associated with NMDA-NR2 phosphorylation in the hippocampus 65 and this phenomenon was reduced in σ 1 R KO mice 23 .…”

Section: Discussionmentioning

confidence: 99%

Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice

Castany

Gris

Vela

et al. 2018

Sci Rep

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Sigma-1 receptor (σ1R) knockout (KO) CD1 mice, generated by homologous recombination, and separate pharmacological studies in wild type (WT) mice were done to investigate the role of this receptor in the development of pain-related behaviours (thermal hyperalgesia and mechanical allodynia) in mice after spinal cord contusion injury (SCI) – a model of central neuropathic pain. The modulatory effect of σ1R KO on extracellular mediators and signalling pathways in the spinal cord was also investigated. In particular, changes in the expression of inflammatory cytokines (tumour necrosis factor TNF-α, interleukin IL-1β) and both the expression and activation (phosphorylation) of the N-methyl-D-aspartate receptor subunit 2B (NR2B-NMDA) and extracellular signal-regulated kinases (ERK1/2) were analysed. Compared with WT mice, both mechanical and thermal hypersensitivity were attenuated in σ1R KO mice following SCI. Accordingly, treatment of WT mice with the σ1R antagonist MR309 (previously developed as E-52862; S1RA) after SCI exerted antinociceptive effects (i.e. reduced mechanical allodynia and thermal hyperalgesia). Attenuated nociceptive responses in σ1R KO were accompanied by reduced expression of TNF- α and IL-1β as well as decreased activation/phosphorylation of NR2B-NMDA receptors and ERK1/2. These findings suggest that σ1R may modulate central neuropathic pain and point to regulation of sensitization-related phenomena as a possible mechanism.

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“…The air-puff threshold was determined as the air-puff pressure at which each rat responded in 50% of the trials. The cut-off pressure for the air puff was 40 psi, as described previously [ 21 22 23 24 ]. The naïve rats did not respond to a pressure of less than 40 psi.…”

Section: Methodsmentioning

confidence: 99%

Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats

Yoon

Son

Kim

et al. 2018

Korean J Physiol Pharmacol

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The aim of the present study was to examine the effects of preemptive analgesia on the development of trigeminal neuropathic pain. For this purpose, mechanical allodynia was evaluated in male Sprague-Dawley rats using chronic constriction injury of the infraorbital nerve (CCI-ION) and perineural application of 2% QX-314 to the infraorbital nerve. CCI-ION produced severe mechanical allodynia, which was maintained until postoperative day (POD) 30. An immediate single application of 2% QX-314 to the infraorbital nerve following CCI-ION significantly reduced neuropathic mechanical allodynia. Immediate double application of QX-314 produced a greater attenuation of mechanical allodynia than a single application of QX-314. Immediate double application of 2% QX-314 reduced the CCI-ION-induced upregulation of GFAP and p-p38 expression in the trigeminal ganglion. The upregulated p-p38 expression was co-localized with NeuN, a neuronal cell marker. We also investigated the role of voltage-gated sodium channels (Navs) in the antinociception produced by preemptive application of QX-314 through analysis of the changes in Nav expression in the trigeminal ganglion following CCI-ION. Preemptive application of QX-314 significantly reduced the upregulation of Nav1.3, 1.7, and 1.9 produced by CCI-ION. These results suggest that long-lasting blockade of the transmission of pain signaling inhibits the development of neuropathic pain through the regulation of Nav isoform expression in the trigeminal ganglion. Importantly, these results provide a potential preemptive therapeutic strategy for the treatment of neuropathic pain after nerve injury.

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Intracisternal Administration of NR2 Subunit Antagonists Attenuates the Nociceptive Behavior and p-p38 MAPK Expression Produced by Compression of the Trigeminal Nerve Root

Cited by 22 publications

References 51 publications

Role of glutamate receptors in the dorsal reticular nucleus in formalin‐induced secondary allodynia

Role of glutamate receptors in the dorsal reticular nucleus in formalin‐induced secondary allodynia

Critical role of sigma-1 receptors in central neuropathic pain-related behaviours after mild spinal cord injury in mice

Preemptive application of QX-314 attenuates trigeminal neuropathic mechanical allodynia in rats

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