The need for fundamental reforms in the pain research field to develop innovative drugs

References

• Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006;10(4):287–333. DOI:10.1016/j.ejpain.2005.06.009
   PubMed Web of Science ®Google Scholar
• van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology - where do lifestyle factors fit in? Br J Pain. 2013;7(4):209–217. DOI:10.1177/2049463713493264
   PubMedGoogle Scholar
• Reid KJ, Harker J, Bala MM, et al. Epidemiology of chronic non-cancer pain in Europe: narrative review of prevalence, pain treatments and pain impact. Curr Med Res Opin. 2011;27(2):449–462. DOI:10.1185/03007995.2010.545813
   PubMed Web of Science ®Google Scholar
• Gaskin DJ, Richard P. The economic costs of pain in the United States. J Pain. 2012;13(8):715–724. DOI:10.1016/j.jpain.2012.03.009
   PubMed Web of Science ®Google Scholar
• Woolf CJ. What is this thing called pain? J Clin Invest. 2010;120(11):3742–3744. DOI:10.1172/JCI45178
   PubMed Web of Science ®Google Scholar
• Woolf CJ. Overcoming obstacles to developing new analgesics. Nat Med. 2010;16(11):1241–1247. DOI:10.1038/nm.2230
   PubMed Web of Science ®Google Scholar
• Kissin I. The development of new analgesics over the past 50 years: a lack of real breakthrough drugs. Anesth Analg. 2010;110(3):780–789. DOI:10.1213/ANE.0b013e3181cde882
   PubMed Web of Science ®Google Scholar
• Baron R, Binder A, Attal N, et al. Neuropathic low back pain in clinical practice. Eur J Pain. 2016;20(6):861–873. DOI:10.1002/ejp.838
   PubMed Web of Science ®Google Scholar
• Ablin JN, Häuser W. Fibromyalgia syndrome: novel therapeutic targets. Pain Manag. 2016;6(4):371–381. DOI:10.2217/pmt-2016-0007
   PubMed Web of Science ®Google Scholar
• Nagakura Y. Challenges in drug discovery for overcoming ‘dysfunctional pain’: an emerging category of chronic pain. Expert Opin Drug Discov. 2015;10(10):1043–1045. DOI:10.1517/17460441.2015.1066776
   PubMed Web of Science ®Google Scholar
• Kissin I. Scientometrics of drug discovery efforts: pain-related molecular targets. Drug Des Devel Ther. 2015;9:3393–3404. DOI:10.2147/DDDT.S85633
   PubMed Web of Science ®Google Scholar
• Hsu E, Murphy S, Chang D, et al. Expert opinion on emerging drugs: chronic low back pain. Expert Opin Emerg Drugs. 2015;20(1):103–127. DOI:10.1517/14728214.2015.993379
   PubMed Web of Science ®Google Scholar
• Smith MT, Muralidharan A. Targeting angiotensin II type 2 receptor pathways to treat neuropathic pain and inflammatory pain. Expert Opin Ther Targets. 2015;19(1):25–35. DOI:10.1517/14728222.2014.957673
   PubMed Web of Science ®Google Scholar
• McGivern JG. Ziconotide: a review of its pharmacology and use in the treatment of pain. Neuropsychiatr Dis Treat. 2007;3(1):69–85.
   PubMedGoogle Scholar
• Miller RE, Block JA, Malfait AM. Nerve growth factor blockade for the management of osteoarthritis pain: what can we learn from clinical trials and preclinical models?. Curr Opin Rheumatol. 2016;(Epub ahead of print).
   PubMedGoogle Scholar
• Goldstein DJ, Wang O, Gitter BD, et al. Dose-response study of the analgesic effect of lanepitant in patients with painful diabetic neuropathy. Clin Neuropharmacol. 2001;24(1):16–22.
   PubMed Web of Science ®Google Scholar
• Wallace MS, Rowbotham MC, Katz NP, et al. A randomized, double-blind, placebo-controlled trial of a glycine antagonist in neuropathic pain. Neurology. 2002;59(11):1694–1700.
   PubMed Web of Science ®Google Scholar
• Coudoré-Civiale MA, Courteix C, Eschalier A, et al. Effect of tachykinin receptor antagonists in experimental neuropathic pain. Eur J Pharmacol. 1998;361(2–3):175–184.
   PubMed Web of Science ®Google Scholar
• Quartaroli M, Fasdelli N, Bettelini L, et al. GV196771A, an NMDA receptor/glycine site antagonist, attenuates mechanical allodynia in neuropathic rats and reduces tolerance induced by morphine in mice. Eur J Pharmacol. 2001;430(2–3):219–227.
   PubMed Web of Science ®Google Scholar
• Blackburn-Munro G. Pain-like behaviours in animals - how human are they? Trends Pharmacol Sci. 2004;25(6):299–305. DOI:10.1016/j.tips.2004.04.008
   PubMed Web of Science ®Google Scholar
• Negus SS, Vanderah TW, Brandt MR, et al. Preclinical assessment of candidate analgesic drugs: recent advances and future challenges. J Pharmacol Exp Ther. 2006;319(2):507–514. DOI:10.1124/jpet.106.106377
   PubMed Web of Science ®Google Scholar
• Rice AS, Cimino-Brown D, Eisenach JC, et al. Animal models and the prediction of efficacy in clinical trials of analgesic drugs: a critical appraisal and call for uniform reporting standards. Pain. 2008;139(2):243–247. DOI:10.1016/j.pain.2008.08.017
   PubMed Web of Science ®Google Scholar
• Prinz F, Schlange T, Asadullah K. Believe it or not: how much can we rely on published data on potential drug targets? Nat Rev Drug Discov. 2011;10(9):712. DOI:10.1038/nrd3439-c1
   PubMed Web of Science ®Google Scholar
• Yaksh TL, Ozaki G, McCumber D, et al. An automated flinch detecting system for use in the formalin nociceptive bioassay. J Appl Physiol. 2001;90(6):2386–2402.
   PubMed Web of Science ®Google Scholar
• Kawasaki-Yatsugi S, Nagakura Y, Ogino S, et al. Automated measurement of spontaneous pain-associated limb movement and drug efficacy evaluation in a rat model of neuropathic pain. Eur J Pain. 2012;16(10):1426–1436. DOI:10.1002/j.1532-2149.2012.00142.x
   PubMed Web of Science ®Google Scholar
• Langford DJ, Bailey AL, Chanda ML, et al. Coding of facial expressions of pain in the laboratory mouse. Nat Methods. 2010;7(6):447–449. DOI:10.1038/nmeth.1455
   PubMed Web of Science ®Google Scholar
• Sotocinal SG, Sorge RE, Zaloum A, et al. The rat grimace scale: a partially automated method for quantifying pain in the laboratory rat via facial expressions. Mol Pain. 2011;7:55. DOI:10.1186/1744-8069-7-55
   PubMed Web of Science ®Google Scholar
• Angeby-Möller K, Berge OG, Hamers FP. Using the CatWalk method to assess weight-bearing and pain behaviour in walking rats with ankle joint monoarthritis induced by carrageenan: effects of morphine and rofecoxib. J Neurosci Methods. 2008;174(1):1–9. DOI:10.1016/j.jneumeth.2008.06.017
   PubMed Web of Science ®Google Scholar
• Ferreira-Gomes J, Adães S, Castro-Lopes JM. Assessment of movement-evoked pain in osteoarthritis by the knee-bend and CatWalk tests: a clinically relevant study. J Pain. 2008;9(10):945–954. DOI:10.1016/j.jpain.2008.05.012
   PubMed Web of Science ®Google Scholar
• King T, Vera-Portocarrero L, Gutierrez T, et al. Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci. 2009;12(11):1364–1366. DOI:10.1038/nn.2407
   PubMed Web of Science ®Google Scholar
• He Y, Tian X, Hu X, et al. Negative reinforcement reveals non-evoked ongoing pain in mice with tissue or nerve injury. J Pain. 2012;13(6):598–607. DOI:10.1016/j.jpain.2012.03.011
   PubMed Web of Science ®Google Scholar
• Martin TJ, Kim SA, Eisenach JC. Clonidine maintains intrathecal self-administration in rats following spinal nerve ligation. Pain. 2006;125(3):257–263. DOI:10.1016/j.pain.2006.05.027
   PubMed Web of Science ®Google Scholar
• Andrews N, Legg E, Lisak D, et al. Spontaneous burrowing behaviour in the rat is reduced by peripheral nerve injury or inflammation associated pain. Eur J Pain. 2012;16(4):485–495. DOI:10.1016/j.ejpain.2011.07.012
   PubMed Web of Science ®Google Scholar
• Backonja MM, Stacey B. Neuropathic pain symptoms relative to overall pain rating. J Pain. 2004;5(9):491–497. DOI:10.1016/j.jpain.2004.09.001
   PubMed Web of Science ®Google Scholar
• Mannion AF, Balagué F, Pellisé F, et al. Pain measurement in patients with low back pain. Nat Clin Pract Rheumatol. 2007;3(11):610–618. DOI:10.1038/ncprheum0646
   PubMedGoogle Scholar
• Percie Du Sert N, Rice AS. Improving the translation of analgesic drugs to the clinic: animal models of neuropathic pain. Br J Pharmacol. 2014;171(12):2951–2963. DOI:10.1111/bph.12645
   PubMed Web of Science ®Google Scholar
• Tappe-Theodor A, Kuner R. Studying ongoing and spontaneous pain in rodents–challenges and opportunities. Eur J Neurosci. 2014;39(11):1881–1890. DOI:10.1111/ejn.12643
   PubMed Web of Science ®Google Scholar
• Freeman R, Durso-Decruz E, Emir B. Efficacy, safety, and tolerability of pregabalin treatment for painful diabetic peripheral neuropathy: findings from seven randomized, controlled trials across a range of doses. Diabetes Care. 2008;31(7):1448–1454. DOI:10.2337/dc07-2105
   PubMed Web of Science ®Google Scholar
• Da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2016;387(10033):2093–2105. DOI:10.1016/S0140-6736(16)30002-2
   PubMed Web of Science ®Google Scholar
• Moore RA, Cai N, Skljarevski V, et al. Duloxetine use in chronic painful conditions - individual patient data responder analysis. Eur J Pain. 2014;18(1):67–75. DOI:10.1002/j.1532-2149.2013.00341.x
   PubMed Web of Science ®Google Scholar
• Le Cudennec C, Castagné V. Face-to-face comparison of the predictive validity of two models of neuropathic pain in the rat: analgesic activity of pregabalin, tramadol and duloxetine. Eur J Pharmacol. 2014;735:17–25. DOI:10.1016/j.ejphar.2014.04.003
   PubMed Web of Science ®Google Scholar
• Yamamoto H, Shimoshige Y, Yamaji T, et al. Pharmacological characterization of standard analgesics on mechanical allodynia in streptozotocin-induced diabetic rats. Neuropharmacology. 2009;57(4):403–408. DOI:10.1016/j.neuropharm.2009.06.037
   PubMed Web of Science ®Google Scholar
• Mixcoatl-Zecuatl T, Jolivalt CG. A spinal mechanism of action for duloxetine in a rat model of painful diabetic neuropathy. Br J Pharmacol. 2011;164(1):159–169. DOI:10.1111/j.1476-5381.2011.01334.x
   PubMed Web of Science ®Google Scholar
• Matson DJ, Broom DC, Carson SR, et al. Inflammation-induced reduction of spontaneous activity by adjuvant: a novel model to study the effect of analgesics in rats. J Pharmacol Exp Ther. 2007;320(1):194–201. DOI:10.1124/jpet.106.109736
   PubMed Web of Science ®Google Scholar
• Ferber G. Biomarkers and proof of concept. Methods Find Exp Clin Pharmacol. 2002;24(Suppl C):35–40.
   PubMedGoogle Scholar
• Pedersen TR. The success story of LDL cholesterol lowering. Circ Res. 2016;118(4):721–731. DOI:10.1161/CIRCRESAHA.115.306297
   PubMed Web of Science ®Google Scholar
• Bhardwaj G. How the antihypertensive losartan was discovered. Expert Opin Drug Discov. 2006;1(6):609–618. DOI:10.1517/17460441.1.6.609
   PubMed Web of Science ®Google Scholar
• Smith CG, Vane JR. The discovery of captopril. Faseb J. 2003;17(8):788–789. DOI:10.1096/fj.03-0093life
   PubMed Web of Science ®Google Scholar
• Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65(3):385–411.
   PubMed Web of Science ®Google Scholar
• Sakoğlu U, Upadhyay J, Chin CL, et al. Paradigm shift in translational neuroimaging of CNS disorders. Biochem Pharmacol. 2011;81(12):1374–1387. DOI:10.1016/j.bcp.2010.12.029
   PubMed Web of Science ®Google Scholar
• Napadow V, Harris RE. What has functional connectivity and chemical neuroimaging in fibromyalgia taught us about the mechanisms and management of ‘centralized’ pain? Arthritis Res Ther. 2014;16(5):425. DOI:10.1186/s13075-014-0425-0
   PubMed Web of Science ®Google Scholar
• Napadow V, LaCount L, Park K, et al. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis Rheum. 2010;62(8):2545–2555. DOI:10.1002/art.27497
   PubMed Web of Science ®Google Scholar
• Schmidt-Wilcke T, Ichesco E, Hampson JP, et al. Resting state connectivity correlates with drug and placebo response in fibromyalgia patients. Neuroimage Clin. 2014;6:252–261. DOI:10.1016/j.nicl.2014.09.007
   PubMed Web of Science ®Google Scholar
• Hong JY, Kilpatrick LA, Labus JS, et al. Sex and disease-related alterations of anterior insula functional connectivity in chronic abdominal pain. J Neurosci. 2014;34(43):14252–14259. DOI:10.1523/JNEUROSCI.1683-14.2014
   PubMed Web of Science ®Google Scholar
• Liu J, Hao Y, Du M, et al. Quantitative cerebral blood flow mapping and functional connectivity of postherpetic neuralgia pain: a perfusion fMRI study. Pain. 2013;154(1):110–118. DOI:10.1016/j.pain.2012.09.016
   PubMed Web of Science ®Google Scholar
• Howard MA, Sanders D, Krause K, et al. Alterations in resting-state regional cerebral blood flow demonstrate ongoing pain in osteoarthritis: an arterial spin-labeled magnetic resonance imaging study. Arthritis Rheum. 2012;64(12):3936–3946. DOI:10.1002/art.37685
   PubMed Web of Science ®Google Scholar
• Baliki MN, Chang PC, Baria AT, et al. Resting-sate functional reorganization of the rat limbic system following neuropathic injury. Sci Rep. 2014;4:6186. DOI:10.1038/srep06186
   PubMed Web of Science ®Google Scholar
• Chang PC, Pollema-Mays SL, Centeno MV, et al. Role of nucleus accumbens in neuropathic pain: linked multi-scale evidence in the rat transitioning to neuropathic pain. Pain. 2014;155(6):1128–1139. DOI:10.1016/j.pain.2014.02.019
   PubMed Web of Science ®Google Scholar
• Upadhyay J, Baker SJ, Rajagovindan R, et al. Pharmacological modulation of brain activity in a preclinical model of osteoarthritis. Neuroimage. 2013;64:341–355. DOI:10.1016/j.neuroimage.2012.08.084
   PubMed Web of Science ®Google Scholar
• Abaei M, Sagar DR, Stockley EG, et al. Neural correlates of hyperalgesia in the monosodium iodoacetate model of osteoarthritis pain. Mol Pain. 2016;12.
   PubMed Web of Science ®Google Scholar
• Hooker BA, Tobon G, Baker SJ, et al. Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain. Eur J Pain. 2014;18(2):223–237. DOI:10.1002/j.1532-2149.2013.00364.x
   PubMed Web of Science ®Google Scholar
• Mao J. Current challenges in translational pain research. Trends Pharmacol Sci. 2012;33(11):568–573. DOI:10.1016/j.tips.2012.08.001
   PubMed Web of Science ®Google Scholar
• Spierings EL, Fidelholtz J, Wolfram G, et al. A phase III placebo- and oxycodone-controlled study of tanezumab in adults with osteoarthritis pain of the hip or knee. Pain. 2013;154(9):1603–1612. DOI:10.1016/j.pain.2013.04.035
   PubMed Web of Science ®Google Scholar
• Sanga P, Polverejan E, Wang S, et al. Efficacy, safety, and tolerability of fulranumab as an adjunctive therapy in patients with inadequately controlled, moderate-to-severe chronic low back pain: a randomized, double-blind, placebo-controlled, dose-ranging, dose-loading phase II study. Clin Ther. 2016;38(6):1435–1450. DOI:10.1016/j.clinthera.2016.03.030
   PubMed Web of Science ®Google Scholar
• Mease PJ, Russell IJ, Arnold LM, et al. A randomized, double-blind, placebo-controlled, phase III trial of pregabalin in the treatment of patients with fibromyalgia. J Rheumatol. 2008;35(3):502–514.
   PubMed Web of Science ®Google Scholar
• Goldstein DJ, Lu Y, Detke MJ, et al. Duloxetine vsplacebo in patients with painful diabetic neuropathy. Pain. 2005;116(1–2):109–118. DOI:10.1016/j.pain.2005.03.029
   PubMed Web of Science ®Google Scholar
• Vellucci R. Heterogeneity of chronic pain. Clin Drug Investig. 2012;32(Suppl 1):3–10. DOI:10.2165/11630030-000000000-00000
   Google Scholar
• Jardim DL, Schwaederle M, Wei C, et al. Impact of a biomarker-based strategy on oncology drug development: a meta-analysis of clinical trials leading to FDA approval. J Natl Cancer Inst. 2015;107(11):djv253.
   PubMedGoogle Scholar
• Fabi A, Malaguti P, Vari S, et al. First-line therapy in HER2 positive metastatic breast cancer: is the mosaic fully completed or are we missing additional pieces? J Exp Clin Cancer Res. 2016;35(1):104. DOI:10.1186/s13046-016-0444-6
   PubMed Web of Science ®Google Scholar
• Garnock-Jones KP, Keating GM, Scott LJ. Trastuzumab: a review of its use as adjuvant treatment in human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Drugs. 2010;70(2):215–239. DOI:10.2165/11203700-000000000-00000
   PubMed Web of Science ®Google Scholar
• Reimer M, Helfert SM, Baron R. Phenotyping neuropathic pain patients: implications for individual therapy and clinical trials. Curr Opin Support Palliat Care. 2014;8(2):124–129. DOI:10.1097/SPC.0000000000000045
   PubMed Web of Science ®Google Scholar
• Cruz-Almeida Y, Fillingim RB. Can quantitative sensory testing move us closer to mechanism-based pain management? Pain Med. 2014;15(1):61–72. DOI:10.1111/pme.12230
   PubMed Web of Science ®Google Scholar
• Rolke R, Baron R, Maier C, et al. Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values. Pain. 2006;123(3):231–243. DOI:10.1016/j.pain.2006.01.041
   PubMed Web of Science ®Google Scholar
• Edwards RR, Haythornthwaite JA, Tella P, et al. Basal heat pain thresholds predict opioid analgesia in patients with postherpetic neuralgia. Anesthesiology. 2006;104(6):1243–1248.
   PubMed Web of Science ®Google Scholar
• Yarnitsky D, Granot M, Nahman-Averbuch H, et al. Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy. Pain. 2012;153(6):1193–1198. DOI:10.1016/j.pain.2012.02.021
   PubMed Web of Science ®Google Scholar
• Hatcher JP, Chessell IP, Hughes JP. Biologics: the next-generation therapeutics for analgesia? Expert Rev Neurother. 2011;11(11):1653–1658. DOI:10.1586/ern.11.66
   PubMed Web of Science ®Google Scholar
• van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology and its clinical relevance. Br J Anaesth. 2013;111(1):13–18. DOI:10.1093/bja/aet123
   PubMed Web of Science ®Google Scholar
• Sałat K, Kowalczyk P, Gryzło B, et al. New investigational drugs for the treatment of neuropathic pain. Expert Opin Investig Drugs. 2014;23(8):1093–1104. DOI:10.1517/13543784.2014.916688
   PubMed Web of Science ®Google Scholar
• Berge OG. Predictive validity of behavioural animal models for chronic pain. Br J Pharmacol. 2011;164(4):1195–1206. DOI:10.1111/j.1476-5381.2011.01300.x
   PubMed Web of Science ®Google Scholar
• Berg EL. Systems biology in drug discovery and development. Drug Discov Today. 2014;19(2):113–125. DOI:10.1016/j.drudis.2013.10.003
   PubMed Web of Science ®Google Scholar
• Wishart DS. Emerging applications of metabolomics in drug discovery and precision medicine. Nat Rev Drug Discov. 2016;15(7):473–484. DOI:10.1038/nrd.2016.32
   PubMed Web of Science ®Google Scholar
• Gligorijević V, Malod-Dognin N, Pržulj N. Integrative methods for analyzing big data in precision medicine. Proteomics. 2016;16(5):741–758. DOI:10.1002/pmic.201500396
   PubMed Web of Science ®Google Scholar
• Mejia AF, Nebel MB, Shou H, et al. Improving reliability of subject-level resting-state fMRI parcellation with shrinkage estimators. Neuroimage. 2015;112:14–29. DOI:10.1016/j.neuroimage.2015.02.042
   PubMed Web of Science ®Google Scholar
• Salomons TV, Iannetti GD, Liang M, et al. The “pain matrix” in pain-free individuals. JAMA Neurol. 2016;73(6):755–756. DOI:10.1001/jamaneurol.2016.0653
   PubMed Web of Science ®Google Scholar
• Harris RE, Napadow V, Huggins JP, et al. Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients. Anesthesiology. 2013;119(6):1453–1464. DOI:10.1097/ALN.0000000000000017
   PubMed Web of Science ®Google Scholar