Elevated prepronociceptin, nociceptin/orphanin FQ and nocistatin concentrations in rat chronic constriction nerve injury and diabetic neuropathic pain models

Liu, Eugene H.; Li, Chunmei; Govindasamy, Malathi; Neo, Hong Jye; Lee, Tat Leang; Low, Chian Ming; Tachibana, Shinro

doi:10.1016/j.neulet.2011.10.059

Cited by 18 publications

(17 citation statements)

References 15 publications

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“…N/OFQ is expressed widely in brain areas, including those related with nociception ; its high expression in cortex, hypothalamus, locus coeruleus, amygdala, nucleus raphe magnus and PAG is in line with our findings. Moreover, as mentioned earlier, prenociceptin and N/OFQ concentrations were indicated to be significantly high in the brain, spinal cord, and serum of neuropathic rats . A similar increase in N/OFQ immunoreactivity in PAG and amygdala of morphine tolerant rat brain and attenuation of opioid antinociceptive tolerance in ventrolateral PAG with NOP receptor antagonists are consistent with our results and once again point to the similarity between opioids and cannabinoids.…”

Section: Discussionsupporting

confidence: 92%

“…Common intracellular mechanisms are suggested to be involved in neuropathic pain and opioid tolerance [30,31]. Additionally, elevated N/OFQ levels are observed not only in brains of neuropathic rats but also in morphine-tolerated animals [32][33][34][35]; in line with these reports, NOP receptor antagonists prevented the development of morphine tolerance [32,36]. Considering the similarities between opioids and cannabinoids, such findings may also be obtained with long-term use of cannabinoids.…”

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confidence: 65%

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Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance

Ulugöl

Topuz

Gündüz

et al. 2016

Fundamemntal Clinical Pharma

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It has been indicated that acute and chronic morphine administrations enhance nociceptin/orphanin FQ (N/OFQ) levels in the brain, which might play role in the development of tolerance to the antinociceptive effect of morphine. Accordingly, N/OFQ receptor (NOP) antagonists have been shown to prevent the development of antinociceptive tolerance to morphine. Our aim is to observe whether cannabinoids, similarly to opioids, enhance N/OFQ levels in pain-related brain regions and whether antagonism of NOP receptors attenuates the development of tolerance to the antinociceptive effect of cannabinoids. Hot plate and Tail flick tests are used to assess the antinociceptive response in Sprague-Dawley rats. N/OFQ levels are measured in cortex, amygdala, hypothalamus, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains using Western blotting and immunohistochemistry. Within 9 days, animals became completely tolerant to the antinociceptive effect of the cannabinoid agonist WIN 55,212-2 (2, 4, 6 mg/kg, i.p.). Chronic administration of JTC-801, a NOP receptor antagonist, at a dose that exerted no effect on its own (1 mg/kg, i.p.), attenuated development of tolerance to the antinociceptive effect of WIN 55,212-2 (4 mg/kg, i.p.). Western blotting and immunohistochemistry results showed that N/OFQ levels significantly increased in amygdala, periaqueductal gray, nucleus raphe magnus and locus coeruleus of rat brains when WIN 55,212-2 was combined with JTC-801. We hypothesize that, similar to opioids, chronic cannabinoid + NOP antagonist administration may enhance N/OFQ levels and NOP receptor antagonism prevents development of tolerance to cannabinoid antinociception.

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 65%

Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance

Ulugöl

Topuz

Gündüz

et al. 2016

Fundamemntal Clinical Pharma

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“…Taken together, these results indicate that low doses of N/OFQ induce allodynia via JNK activation in the spinal cord. The N/OFQ concentration is 36 fmol/mg protein in the spinal cord, and it is approximately five-fold higher in the spinal cord of neuropathic pain models involving chronic constriction nerve injury and streptozotocin-induced diabetic rats (Liu et al, 2012). In humans, the N/OFQ concentrations are 30 fmol/mg in the spinal dorsal horn (Witta et al, 2004), 45 fmol/mL in the cerebrospinal fluid (Raffaeli et al, 2006), and 11 pg/mL (6 fmol/mL) in the serum (Ko et al, 2002).…”

Section: N/ofq-induced Allodynia Via Jnk Activation In the Spinal Cordmentioning

confidence: 99%

Intrathecal administration of low‐dose nociceptin/orphanin FQ induces allodynia via c‐Jun N‐terminal kinase and monocyte chemoattractant protein‐1

Kawabata

Nishimura

Fujiwara

et al. 2016

Eur J of Neuroscience

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Pathological chronic pain, which is frequently associated with prolonged tissue damage, inflammation, tumour invasion, and neurodegenerative diseases, gives rise to hyperalgesia and allodynia. We previously reported that intrathecal administration of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like receptor, in the femtomole range induces touch-evoked allodynia. N/OFQ has been implicated in multiple signalling pathways, such as inhibition of cAMP production and Ca(2+) channels, or activation of K(+) channels and mitogen-activated protein kinase, although the signalling pathways of N/OFQ-induced allodynia remain unclear. To address these issues, we developed an ex vivo mitogen-activated protein kinase assay by using intact slices of mouse spinal cord. N/OFQ markedly increased the phosphorylation of c-Jun N-terminal kinase (JNK) in the superficial dorsal horn of the spinal cord. The N/OFQ-stimulated JNK phosphorylation was significantly inhibited by pertussis toxin, the phospholipase C inhibitor U73122, and the inositol trisphosphate receptor antagonist Xestospongin C. Intrathecal administration of the JNK inhibitor SP600125 inhibited N/OFQ-evoked allodynia. The N/OFQ-induced increase in JNK phosphorylation was observed in astrocytes that expressed glial fibrillary acidic protein. N/OFQ also induced monocyte chemoattractant protein-1 (MCP-1) release via the JNK pathway, and N/OFQ-induced JNK phosphorylation was observed in MCP-1-immunoreactive astrocytes. Intrathecal administration of the MCP-1 receptor antagonist RS504393 inhibited N/OFQ-evoked allodynia. These results suggest that, in the spinal dorsal horn, N/OFQ induces allodynia through activation of JNK via the phospholipase C-inositol trisphosphate pathway, which is coupled to pertussis toxin-sensitive G-protein, and following the release of MCP-1 from astrocytes.

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“…Notably, in the spinal cord and in dorsal root ganglia of rats subjected to the sciatic nerve chronic constriction injury (CCI), an upregulation of prepro-N/OFQ and NOP receptor mRNA levels has been reported (Briscini et al 2002;Liu et al 2012). Notably, in the spinal cord and in dorsal root ganglia of rats subjected to the sciatic nerve chronic constriction injury (CCI), an upregulation of prepro-N/OFQ and NOP receptor mRNA levels has been reported (Briscini et al 2002;Liu et al 2012).…”

mentioning

confidence: 99%

N/OFQ system in brain areas of nerve‐injured mice: its role in different aspects of neuropathic pain

Palmisano

Mercatelli

Caputi

et al. 2017

Genes Brain and Behavior

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Several studies showed that chronic pain causes reorganization and functional alterations of supraspinal brain regions. The nociceptin-NOP receptor system is one of the major systems involved in pain control and much evidence also suggested its implication in stress, anxiety and depression. Therefore, we investigated the nociceptin-NOP system alterations in selected brain regions in a neuropathic pain murine model. Fourteen days after the common sciatic nerve ligature, polymerase chain reaction (PCR) analysis indicated a significant decrease of pronociceptin and NOP receptor mRNA levels in the thalamus; these alterations could contribute to the decrease of the thalamic inhibitory function reported in neuropathic pain condition. Nociceptin peptide and NOP mRNA increased in the anterior cingulate cortex (ACC) and not in the somatosensory cortex, suggesting a peculiar involvement of this system in pain regulating circuitry. Similarly to the ACC, an increase of nociceptin peptide levels was observed in the amygdala. Finally, the pronociceptin and NOP mRNAs decrease observed in the hypothalamus reflects the lack of hypothalamus-pituitary-adrenal axis activation, already reported in neuropathic pain models. Our data indicate that neuropathic pain conditions affect the supraspinal nociceptin-NOP system which is also altered in regions known to play a role in emotional aspects of pain.

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Elevated prepronociceptin, nociceptin/orphanin FQ and nocistatin concentrations in rat chronic constriction nerve injury and diabetic neuropathic pain models

Cited by 18 publications

References 15 publications

Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance

Changes in nociceptin/orphanin FQ levels in rat brain regions after acute and chronic cannabinoid treatment in conjunction with the development of antinociceptive tolerance

Intrathecal administration of low‐dose nociceptin/orphanin FQ induces allodynia via c‐Jun N‐terminal kinase and monocyte chemoattractant protein‐1

N/OFQ system in brain areas of nerve‐injured mice: its role in different aspects of neuropathic pain

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