ArticleMolecular pain2011
On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats.
Article in Molecular pain, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 35 citations in OpenAlex.
- Critical Role of p38α MAPK Subclass in the Development of Pain Hypersensitivity After Hind Paw Incision.Journal of pain research · 2025Article
- Advances in Neuropathic Pain Research: Selected Intracellular Factors as Potential Targets for Multidirectional Analgesics.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Calcium/calmodulin-dependent protein kinase II is involved in the transmission and regulation of nociception in naïve and morphine-tolerant rat nucleus accumbens.The Korean journal of pain · 2023Article
- Adult spinal Dmrt3 neurons receive direct somatosensory inputs from ipsi- and contralateral primary afferents and from brainstem motor nuclei.The Journal of comparative neurology · 2023Article
- Circular RNA expression profile in the spinal cord of morphine tolerated rats and screen of putative key circRNAs.Molecular brain · 2019Article
- Emerging roles of microRNAs in morphine tolerance.Journal of pain research · 2019Article
- CGRP receptor antagonist activity of olcegepant depends on the signalling pathway measured.Cephalalgia : an international journal of headache · 2018Article
- Sonic hedgehog signaling in spinal cord contributes to morphine-induced hyperalgesia and tolerance through upregulating brain-derived neurotrophic factor expression.Journal of pain research · 2018Article
- Cyclosporin A attenuating morphine tolerance through inhibiting NO/ERK signaling pathway in human glioblastoma cell line: the involvement of calcineurin.EXCLI journal · 2018Article
- Effects of lncRNA uc.48+ siRNA on the release of CGRP in the spinal cords of rats with diabetic neuropathic pain.International journal of clinical and experimental pathology · 2017Article
- siRNA capsulated brain-targeted nanoparticles specifically knock down OATP2B1 in mice: a mechanism for acute morphine tolerance suppression.Scientific reports · 2016Article
- Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ.Molecular pain · 2016Article
- Current gene therapy using viral vectors for chronic pain.Molecular pain · 2015Review
- Attenuation of morphine analgesic tolerance by rosuvastatin in naïve and morphine tolerance rats.Inflammation · 2015Article
- Decreased microRNA-125a-3p contributes to upregulation of p38 MAPK in rat trigeminal ganglions with orofacial inflammatory pain.PloS one · 2014Article
- Opiate exposure and withdrawal induces a molecular memory switch in the basolateral amygdala between ERK1/2 and CaMKIIα-dependent signaling substrates.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance.Pharmacological reviews · 2013Review
- Metabolomics uncovers dietary omega-3 fatty acid-derived metabolites implicated in anti-nociceptive responses after experimental spinal cord injury.Neuroscience · 2013Article
- Inhibition of mTOR/S6K1/Gli1 signaling alleviates morphine-induced thermal hyperalgesia and tolerance.Molecular painArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe neuropeptide, calcitonin gene-related peptide (CGRP) has been proposed to be a regulator of the development of morphine analgesic tolerance and thereby could be a target to reduce the induction of this phenomenon under clinical conditions. However, the mechanisms of CGRP regulation are unclear. We investigated here the possible role of the extracellular signal-regulated protein kinase (ERK), p38 and calcium/calmodulin-dependent protein kinase II (CaMKII) in CGRP regulation following chronic morphine treatment.
resultsA 7-day treatment with morphine (15 μg/day) led to an increase in CGRP contents in the spinal cord dorsal horn (SCDH) and dorsal root ganglion (DRG) and this effect was prevented by the inhibition of the ERK, p38 or CaMKII pathway. The phosphorylation/activation of ERK, p38 and CaMKII was enhanced in the SCDH following chronic morphine while in DRG only the phosphorylation of CaMKII was increased. Moreover, our chronic morphine treatment up-regulated neuronal nitric oxide synthase (nNOS) levels in the SCDH, an effect blocked by the inhibition of the ERK, p38 or CaMKII pathway. The blockade of nNOS activity also suppressed chronic morphine-induced CGRP increases in the DRG and SCDH. Double immunofluorescence studies revealed that nNOS and CaMKII are co-localized in the SCDH and that CaMKII is activated in CGRP-expressing DRG neurons.
conclusionsThe activation of spinal ERK, p38 and CaMKII, alongside nNOS, is involved in chronic morphine-induced CGRP up-regulation in both the DRG and SCDH. Moreover, the stimulation of CaMKII in the DRG likely directly regulates the expression of CGRP associated with morphine analgesic tolerance.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.