Neuropathic pain and temporal expression of preprodynorphin, protein kinase C and N-methyl-d-aspartate receptor subunits after spinal cord injury

Labombarda, Florencia; Coronel, Marı́a Florencia; Villar, Marcelo J.; Nicola, Alejandro F. De; González, Susana

doi:10.1016/j.neulet.2008.09.062

Cited by 28 publications

(26 citation statements)

References 32 publications

(44 reference statements)

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“…Surprisingly, seven days following sciatic nerve injury mRNA of the NMDAR subunits NR1, NR2A and NR2B are not markedly elevated above the levels observed in uninjured animals, despite the fact that the maximum measurable amount of allodynia was reached. Similar observations are described in 2 other models of NP, where a significant NMDA receptor upregulation did not occur until after 14 days of NP following spinal cord injury for NR1, NR2A and NR2B [24], or where a reduction of the NMDA receptor at peak levels of allodynia was observed [25]. In our study, ketamine treatment significantly reduces the mRNA of all the NMDA receptor subunits to expression levels comparable to those of naïve animals, in contrast to the slightly elevated levels of untreated controls.…”

Section: Discussionsupporting

confidence: 83%

Ketamine Does Not Produce Relief of Neuropathic Pain in Mice Lacking the β-Common Receptor (CD131)

et al. 2013

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Neuropathic pain (NP) is a debilitating condition associated with traumatic, metabolic, autoimmune and neurological etiologies. Although the triggers for NP are diverse, there are common underlying pathways, including activation of immune cells in the spinal cord and up-regulation of the N-methyl-D-aspartate receptor (NMDAR). Ketamine, a well-known NDMAR antagonist, reduces neuropathic pain in a sustained manner. Recent study has shown that the novel 11-amino acid peptide erythropoietin derivative ARA290 produces a similar, long-lasting relief of NP. Here, we show that both drugs also have similar effects on the expression of mRNA of the NMDAR, as well as that of microglia, astrocytes and chemokine (C-C motif) ligand 2, all-important contributors to the development of NP. Although the effects of ketamine and ARA 290 on NP and its molecular mediators suggest a common mechanism of action, ARA 290 has no affinity for the NMDAR and acts specifically via the innate repair receptor (IRR) involved in tissue protection. We speculated therefore, that the IRR might be critically involved in the action of ketamine on neuropathic pain. To evaluate this, we studied the effects of ketamine and ARA 290 on acute pain, side effects, and allodynia following a spared nerve injury model in mice lacking the β-common receptor (βcR), a structural component of the IRR. Ketamine (50 mg/kg) and ARA 290 (30 µg/kg) produced divergent effects on acute pain: ketamine produced profound antinociception accompanied with psychomotor side effects, but ARA290 did not, in both normal and knock out mice. In contrast, while both drugs were antiallodynic in WT mice, they had no effect on NP in mice lacking the βcR. Together, these results show that an intact IRR is required for the effective treatment of NP with either ketamine or ARA 290, but is not involved in ketamine’s analgesic and side effects.

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Section: Discussionsupporting

confidence: 83%

Ketamine Does Not Produce Relief of Neuropathic Pain in Mice Lacking the β-Common Receptor (CD131)

et al. 2013

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“…Numerous receptors related to GPCRs interfere with the action of ion channels, and therefore influence the action of PKC, the glutamate transporter (EAAT3), phosphatidylinositol 3-kinase (PI3K), MAPKs, CREB, and many others that are intracellular signaling proteins [22]. According to Labombarda et al [23], in consideration of the observed increase in PKC and NMDA receptors after damage to spinal nerves, the quantitative increase and activation of the NMDA receptor is critical in developing and prolonging neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats

Kwon

Yeom

Joo

2014

Korean J Anesthesiol

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BackgroundNeuropathic rats created by spinal nerve ligation are known to show higher levels of p38, c-Jun NH2-terminal kinase, and extracellular signal-regulated kinase p44/42 (ERK 1/2) of the mitogen-activated protein kinases (MAPKs). The authors of this study aimed to understand the effect of ketamine on p38 MAPK and inflammatory responses, as well as its effect on the development of neuropathic pain.MethodsThe neuropathic rats were prepared by Chung's method with Sprague-Dawley rats. The research was carried out on three groups, a sham-operated group, a neuropathic pain and normal saline (NP + NS) group, and a neuropathic pain and ketamine (NP + Keta) group. The normal saline or ketamine was infused into the neuropathic rats through a mini-osmotic pump implanted in the subcutaneous space. After a week, the quantities of phospho-p38, p38 MAPK and pro-inflammatory cytokines were measured and compared through western blots and reverse transcriptase-polymerase chain reaction.ResultsIn comparison to the control group, the NP + NS group showed a significant increase of phospho-p38 and p38 MAPK, as well as of the proinflammatory cytokines, tumor necrosis factor α (TNFα), and intercellular adhesion molecule 1 (ICAM1). However, in the NP + Keta group, phospho-p38, p38 MAPK and TNFα and, ICAM1 were reduced in comparison to the NP + NS group. The paw withdrawal threshold test also showed the trend of recovery from the mechanical allodynia in the NP + Keta group.ConclusionsIn the development of neuropathic pain, p38 MAPK and inflammatory responses are significantly related, and the use of ketamine reduces p38 MAPK and proinflammatory cytokines. Thus, the adequate use of ketamine could be effective for the prevention and treatment of neuropathic pain following peripheral injury.

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“…Behavioural testing was performed by a blinded observer, in all animals: 1 day before surgery, in order to obtain normal baseline values, and at different time points after spinal cord hemisection or sham‐operation, as previously described (Labombarda et al. ; Coronel et al . ,b).…”

Section: Methodsmentioning

confidence: 99%

Progesterone reduces the expression of spinal cyclooxygenase‐2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain

Coronel

Labombarda

Nicola

et al. 2013

European Journal of Pain

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Neuropathic pain and temporal expression of preprodynorphin, protein kinase C and N-methyl-d-aspartate receptor subunits after spinal cord injury

Cited by 28 publications

References 32 publications

Ketamine Does Not Produce Relief of Neuropathic Pain in Mice Lacking the β-Common Receptor (CD131)

Ketamine Does Not Produce Relief of Neuropathic Pain in Mice Lacking the β-Common Receptor (CD131)

Ketamine reduces the induced spinal p38 MAPK and pro-inflammatory cytokines in a neuropathic rats

Progesterone reduces the expression of spinal cyclooxygenase‐2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain

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