Intra-nucleus accumbens administration of the calcium/calmodulin-dependent protein kinase II inhibitor KN93 induced antinociception in rats with mononeuropathy

Bian, Hui; Yu, Long-Chuan

doi:10.1016/j.neulet.2014.09.007

Cited by 3 publications

(2 citation statements)

References 27 publications

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“…The response to pain of the normal side after mononeuropathy was similar to normal rats as suggested by our results (Fig. 2), thus it is reasonable that the normal side is less sensitive to drug treatments, consistent with our previous study [17] .…”

Section: Resultssupporting

confidence: 92%

Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain

et al. 2015

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Neuropathic pain is of serious clinical concern and only about half of patients achieve partial relief with currently-available treatments, so it is critical to find new drugs for this condition. Recently, the cellsurface trafficking of pain-related receptors has been suggested as an important mechanism underlying persistent neuropathic pain. Here, we used the short peptide GluA2-3y, which specifically inhibits the GluA2-dependent endocytosis of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and tested its anti-nociceptive effect in the periaqueductal grey (PAG) of intact rats and rats with neuropathic pain. Intra-PAG injection of 0.15, 1.5, 7.5, and 15 pmol of GluA2-3y induced dose-dependent increases in hindpaw withdrawal latencies to noxious thermal and mechanical stimuli in intact rats, suggesting that GluA2 cell-surface trafficking in the PAG is involved in pain modulation. Furthermore, GluA2-3y had much stronger anti-nociceptive effects in rats with neuropathic pain induced by sciatic nerve ligation. Interestingly, the intra-PAG injection of 15 pmol GluA2-3y had an analgesic effect similar to 10 μg (35 nmol) morphine in rats with neuropathic pain. Taken together, our results suggested that GluA2 trafficking in the PAG plays a critical role in pain modulation, and inhibiting GluA2 endocytosis with GluA2-3y has potent analgesic effects in rats with neuropathic pain. These findings strongly support the recent hypothesis that targeting receptor trafficking could be a new strategy for the treatment of neuropathic pain.

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Section: Resultssupporting

confidence: 92%

Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain

et al. 2015

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“…Recent pain studies have shown that the NAc also plays a major role in pain modulation and antinociceptive tolerance and acts as a source of analgesia [ 1 , 15 , 16 ]. The authors’ earlier report showed that the microinjection of the CaMK II inhibitor autocamtide-2-related inhibitory peptide (AIP) or KN93 into the NAc alleviates pain that is related to behaviors in the peripheral neuropathic pain model [ 17 , 18 ]. However, the role of CaMK II in the NAc in naïve and morphine-tolerant rats has yet to be the subject of in-depth examination.…”

Section: Introductionmentioning

confidence: 99%

Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens

Chen

Geng

et al. 2023

Korean J Pain

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Background Synaptic plasticity contributes to nociceptive signal transmission and modulation, with calcium/calmodulin-dependent protein kinase II (CaMK II) playing a fundamental role in neural plasticity. This research was conducted to investigate the role of CaMK II in the transmission and regulation of nociceptive information within the nucleus accumbens (NAc) of naïve and morphine-tolerant rats. Methods Randall Selitto and hot-plate tests were utilized to measure the hindpaw withdrawal latencies (HWLs) in response to noxious mechanical and thermal stimuli. To induce chronic morphine tolerance, rats received intraperitoneal morphine injection twice per day for seven days. CaMK II expression and activity were assessed using western blotting. Results Intra-NAc microinjection of autocamtide-2-related inhibitory peptide (AIP) induced an increase in HWLs in naïve rats in response to noxious thermal and mechanical stimuli. Moreover, the expression of the phosphorylated CaMK II (p-CaMK II) was significantly decreased as determined by western blotting. Chronic intraperitoneal injection of morphine resulted in significant morphine tolerance in rats on Day 7, and an increase of p-CaMK II expression in NAc in morphine-tolerant rats was observed. Furthermore, intra-NAc administration of AIP elicited significant antinociceptive responses in morphine-tolerant rats. In addition, compared with naïve rats, AIP induced stronger thermal antinociceptive effects of the same dose in rats exhibiting morphine tolerance. Conclusions This study shows that CaMK II in the NAc is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rats.

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A genetic variant in CAMKK2 gene is possibly associated with increased risk of bipolar disorder

et al. 2015

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A recent large-scale study have reported that rs1063843, a single nucleotide polymorphism located in the CAMKK2 gene is highly associated with schizophrenia in European and Han Chinese populations. Increasing evidences show that schizophrenia and bipolar disorder have some common genetic variance. Here, we evaluated the association of this variant with schizophrenia and bipolar disorder in Iranian population. Genomic DNA was extracted from peripheral blood of 500 schizophrenic patients, 500 bipolar patients and 500 normal controls and all were genotyped for the rs1063843 using a PCR-RFLP method. The allele frequency of rs1063843 was significantly different in both schizophrenia and bipolar patients comparing to control group. For the first time, we showed that rs1063843 is highly associated with bipolar disorder, although more replication studies are needed to confirm our findings. Our results also support the findings of previous studies suggesting a significant association between rs1063843 and schizophrenia.

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Intra-nucleus accumbens administration of the calcium/calmodulin-dependent protein kinase II inhibitor KN93 induced antinociception in rats with mononeuropathy

Cited by 3 publications

References 27 publications

Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain

Pharmacologically inhibiting GluR2 internalization alleviates neuropathic pain

Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens

A genetic variant in CAMKK2 gene is possibly associated with increased risk of bipolar disorder

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