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Responder analysis for pain relief and numbers needed to treat in a meta-analysis of etoricoxib osteoarthritis trials: bridging a gap between clinical trials and clinical practice
Open accessAbstract
Though long-term exposure to nicotine is highly addictive, one "beneficial" consequence of chronic tobacco use is a reduced risk for Parkinson9s disease. Interestingly, these effects both reflect structural and functional plasticity of brain circuits controlling reward and motor behavior, and specifically recruitment of nicotinic acetylcholine receptors (nAChR) in mesencephalic dopaminergic neurons. Since the underlying cellular mechanisms are poorly understood, we addressed this issue employing primary cultures of mouse mesencephalic dopaminergic neurons. Exposure to nicotine (1-10 μM) for 72 hr in vitro increased dendritic arborization and soma size in primary cultures. These effects were blocked by mecamylamine and dihydro-β-erythroidine, but not methyllycaconitine. The involvement of α4β2 nAChR was supported by the lack of nicotine-induced structural remodeling in neurons from α4 null mutant mice (KO). Challenge with nicotine triggered phosphorylation of the extracellular signal-regulated kinase (ERK) and the thymoma viral proto-oncogene (Akt) followed by activation of the mTORC1-dependent p70 ribosomal S6 protein kinase. Upstream pathway blockade using the phosphatidylinositol 3-kinase inhibitor LY294002 resulted in suppression of nicotine-induced phosphorylations and structural plasticity. These effects were dependent upon functional DA D3 receptor (D3R) since nicotine was inactive both in cultures from D3R KO mice and following pharmacologic blockade with D3R antagonist SB-277011-A (50 nM). Finally, exposure to nicotine in utero (5 mg/kg/day for 5 days) resulted in increased soma area of DAergic neurons of newborn mice, effects not observed in D3KO mice. These findings indicate that nicotine-induced structural plasticity in mesencephalic dopaminergic neurons involves α4β2 nAChRs together with dopamine D3R-mediated recruitment of ERK/Akt-mTORC1 signaling.
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“We planned to compare only like with like (where possible); for example in study duration, which can be an additional source of bias if insufficient in length (Moore 2010).”
From Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews (2017) · cites this paper as Moore 2010
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“small studies of fewer than 100 participants per arm (Moore 2010; Nüesch 2010) are at increased risk of succumbing to the random effects in estimating both direction and magnitude of treatment effects”
From Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews (2017) · cites this paper as Moore 2010
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“the z test, [30] comparing different drug/dose combinations only in the trials in which they were used together.”
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Logashina, Y. A., Palikova, Y. A., Паликов, В. А., Kazakov, V. A., Smolskaya, S. V., Dyachenko, I. A., Tarasova, N. V., & Andreev, Y. A. (2021) · Marine Drugs · doi:10.3390/md19010039 · Cited by 45
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Self-citationLevetiracetam for neuropathic pain in adults
Wiffen, P. J., Derry, S., Moore, A., & Lunn, M. P. (2014) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd010943 · Cited by 20
Self-citationTetrahydrocannabinol and Cannabidiol for Pain Treatment—An Update on the Evidence
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Amitriptyline for neuropathic pain and fibromyalgia in adults
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Self-citationCannabinoids for chronic neuropathic pain
Mücke, M., Phillips, T., Radbruch, L., Petzke, F. W., & Häuser, W. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012182 · Cited by 18
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Paracetamol (acetaminophen) with or without codeine or dihydrocodeine for neuropathic pain in adults
Wiffen, P. J., Knaggs, R., Derry, S., Cole, P., Phillips, T., & Moore, R. A. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012227 · Cited by 18
Self-citationMoore, R. A., & Derry, S. (2012) · International Journal of Clinical Practice · doi:10.1111/ijcp.12054 · Cited by 17
Self-citationTreating chronic non-cancer pain in older people – More questions than answers?
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Self-citationMorphine for neuropathic pain in adults
Wiffen, P. J., Carr, D. B., Aldington, D. J., Cole, P., Derry, S., & Moore, R. A. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd011669 · Cited by 17
Self-citationTopical clonidine for neuropathic pain
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der DGRh, K. P., Bolten, W. W., Krüger, K., Reiter-Niesert, S., & Stichtenoth, D. O. (2016) · Zeitschrift für Rheumatologie · doi:10.1007/s00393-015-0018-6 · Cited by 16
Song, Y., He, Q., Huang, W., Yang, L., Zhou, S., Xiao, X., Wang, Z., & Huang, W. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.988070 · Cited by 16
Non-steroidal anti-inflammatory drugs (NSAIDs) for cancer-related pain in children and adolescents
Cooper, T. E., Heathcote, L. C., Anderson, B. J., Grégoire, M.-C., Ljungman, G., & Eccleston, C. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012563 · Cited by 15
Paracetamol (acetaminophen) for chronic non-cancer pain in children and adolescents
Cooper, T. E., Fisher, E., Anderson, B. J., Wilkinson, N. M., Williams, D. G., & Eccleston, C. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012539 · Cited by 15
Hasan, S. B., Gendra, R., James, J. F., Morris, D., Orenstein, L. A. V., & Ingram, J. R. (2022) · British Journal of Dermatology · doi:10.1111/bjd.21821 · Cited by 14
Möller, K. Ä., Berge, O., Finn, A., Stenfors, C., & Svensson, C. I. (2015) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2015.02.050 · Cited by 13
Bello, A. E. (2012) · Therapeutic Advances in Musculoskeletal Disease · doi:10.1177/1759720x12444710 · Cited by 13
Ziebart, C., Nazari, G., & MacDermid, J. C. (2019) · Hand Therapy · doi:10.1177/1758998319865751 · Cited by 13
Wluka, A. E., Urquhart, D. M., Teichtahl, A. J., Hussain, S. M., Forbes, A. B., Arnold, C. A., Wang, Y., & Cicuttini, F. (2021) · BMC Musculoskeletal Disorders · doi:10.1186/s12891-021-04690-y · Cited by 11
Metadata
- Authors
- Moore, R. A., Moore, O. A., Derry, S., Peloso, P. M., Gammaitoni, A. R., & Wang, H.
- Affiliations
- John Radcliffe Hospital (GB)
- Musgrave Park Hospital (GB)
- University of Oxford (GB)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Corresponding author
- Moore, R A
- Moore, O A
- Venue
- Annals of the Rheumatic Diseases
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 69
- Issue
- 2
- Pages
- 374-379
- ISSN
- 0003-4967 (ISSN-L)
- PMC
- PMC2800200
- OpenAlex
- W2103600429
- Cited by
- 279
- References
- 38
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 8 · 2023: 2 · 2022: 9 · 2021: 5 · 2020: 4 · 2019: 14 · 2018: 13 · 2017: 38 · 2016: 27 · 2015: 31 · 2014: 25 · 2013: 32 · 2012: 16
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of the Rheumatic Diseases (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Oxford University Research Archive (ORA) (University of Oxford) (acceptedVersion, cc-by-nc)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Pfizer
- AstraZeneca
- National Institute for Health and Care Research
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Health Sciences › Health Professions › Physical Therapy, Sports Therapy and Rehabilitation › Musculoskeletal pain and rehabilitation
- Keywords
- etoricoxib, osteoarthritis, analgesia, number needed to treat, responder analysis, nicotine, Parkinson's disease risk, nicotinic acetylcholine receptors, alpha4beta2 nAChR, midbrain dopaminergic neurons, dendritic branching, dopamine D3 receptor
- MeSH terms
- Etoricoxib, Diffusion of Innovation, Dose-Response Relationship, Drug, Humans, Pain, Pain Measurement, Pyridines, Sulfones, Osteoarthritis, Hip, Randomized Controlled Trials as Topic, Treatment Outcome, Osteoarthritis, Knee, Cyclooxygenase 2 Inhibitors
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