Pharmacokinetic and pharmacodynamic evaluation of oxycodone and naltrexone for the treatment of chronic lower back pain

References

• Gudin JA, Nalamachu SR. An overview of prodrug technology and its application for developing abuse-deterrent opioids. Postgrad Med. 2016;128:97–105.
   PubMed Web of Science ®Google Scholar
• Setnik B, Goli V, Levy-Cooperman N, et al. Assessing the subjective and physiological effects of intranasally administered crushed extended-release morphine formulations with and without a sequestered naltrexone core in recreational opioid users. Pain Res Manag. 2013;18:e55–62.
   PubMed Web of Science ®Google Scholar
• Setnik B, Sommerville K, Goli V, et al. Assessment of pharmacodynamic effects following oral administration of crushed morphine sulfate and naltrexone hydrochloride extended-release capsules compared with crushed morphine sulfate controlled-release tablets and placebo in nondependent recreational opioid users. Pain Med. 2013;14:1173–1186.
   PubMed Web of Science ®Google Scholar
• Setnik B, Roland CL, Goli V, et al. A clinical trial to determine if corelease of morphine and naltrexone from crushed extended-release capsules induces withdrawal in opioid-dependent patients: a descriptive analysis of six patients. J Opioid Manag. 2013;9:139–150.
   PubMedGoogle Scholar
• Taylor R, Raffa RB, Pergolizzi JV. Opioid formulations with sequestered naltrexone: a perspective review. Ther Adv Drug Saf. 2014;5:129–137.
   PubMedGoogle Scholar
• Burness CB, Keating GM. Oxycodone/Naloxone prolonged-release: a review of its use in the management of chronic pain while counteracting opioid-induced constipation. Drugs. 2014;74:353–375.
   PubMed Web of Science ®Google Scholar
• Blagden M, Hafer J, Duerr H, et al. Long-term evaluation of combined prolonged-release oxycodone and naloxone in patients with moderate-to-severe chronic pain: pooled analysis of extension phases of two Phase III trials. Neurogastroenterol Motil. 2014;26:1792–1801.
   PubMed Web of Science ®Google Scholar
• Smith K, Hopp M, Mundin G, et al. Naloxone as part of a prolonged release oxycodone/naloxone combination reduces oxycodone-induced slowing of gastrointestinal transit in healthy volunteers. Expert Opin Investig Drugs. 2011;20:427–439.
   PubMed Web of Science ®Google Scholar
• Simpson K, Leyendecker P, Hopp M, et al. Fixed-ratio combination oxycodone/naloxone compared with oxycodone alone for the relief of opioid-induced constipation in moderate-to-severe noncancer pain. Curr Med Res Opin. 2008;24:3503–3512.
   PubMed Web of Science ®Google Scholar
• Katz N, Kopecky EA, O’Connor M, et al. A phase 3, multicenter, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ER in patients with moderate-to-severe chronic low back pain. Pain. 2015;156:2458–2467.
   PubMed Web of Science ®Google Scholar
• Ueberall MA, Mueller-Schwefe GH. Development of opioid-induced constipation: post hoc analysis of data from a 12-week prospective, open-label, blinded-endpoint streamlined study in low-back pain patients treated with prolonged-release WHO step III opioids. J Pain Res. 2015;8:459–475.
   PubMed Web of Science ®Google Scholar
• Ueberall MA, Mueller-Schwefe GH. Safety and efficacy of oxycodone/naloxone vs. oxycodone vs. morphine for the treatment of chronic low back pain: results of a 12 week prospective, randomized, open-label blinded endpoint streamlined study with prolonged-release preparations. Curr Med Res Opin. 2015;31:1413–1429.
   PubMed Web of Science ®Google Scholar
• Setnik B, Bramson C, Bass A, et al. Intranasal administration of crushed ALO-02 (extended-release oxycodone with sequestered naltrexone): A randomized, controlled abuse-potential study in nondependent recreational opioid users. J Clin Pharmacol. 2015;55:1351–1361.
   PubMed Web of Science ®Google Scholar
• Rauck RL, Hale ME, Bass A, et al. A randomized double-blind, placebo-controlled efficacy and safety study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) for moderate-to-severe chronic low back pain treatment. Pain. 2015;156:1660–1669.
   PubMed Web of Science ®Google Scholar
• Malhotra BK, Matschke K, Wang Q, et al. Effects of ethanol on the pharmacokinetics of extended-release oxycodone with sequestered naltrexone (ALO-02). Clin Drug Investig. 2015;35:267–274.
   PubMed Web of Science ®Google Scholar
• Arora S, Setnik B, Michael D, et al. A multicenter, 12-month, open-label, single-arm safety study of oxycodone-hydrochloride/naltrexone-hydrochloride extended-release capsules (ALO-02) in patients with moderate-to-severe chronic noncancer pain. J Opioid Manag. 2014;10:423–436.
   PubMedGoogle Scholar
• Gandelman K, Lamson M, Salageanu J, et al. Effect of food on the pharmacokinetics of oxycodone and naltrexone from ALO-02, an extended release formulation of oxycodone with sequestered naltrexone. Clin Pharmacol Drug Dev. 2015;4:370–376.
   PubMed Web of Science ®Google Scholar
• Rauck R, Hale M, Bass A, et al. Efficacy and safety of ALO-02, an extended-release oxycodone surrounding sequestered naltrexone, in the treatment of moderate-to-severe chronic low back pain. J Pain. 2014;15:S78–S78.
   Web of Science ®Google Scholar
• Gandelman K, Lamson M, Salageanu J, et al. Evaluation of the effects of food and of sprinkling pellets on applesauce on the pharmacokinetics of oxycodone and naltrexone from ALO-02, an extended-release formulation of oxycodone with sequestered naltrexone. J Pain. 2014;15:S78–S78.
   Web of Science ®Google Scholar
• Gandelman K, Lamson M, Bramson C, et al. Single- and multiple-dose study to evaluate pharmacokinetics, safety and tolerability of extended-release oxycodone with sequestered naltrexone (ALO-02) in healthy volunteers: a comparison of ALO-02 40 mg twice daily to OxyContin 40 mg twice daily and ALO-02 80 mg once daily. J Pain. 2014;15:S79–S79.
   Web of Science ®Google Scholar
• Setnik B, Bass A, Bramson C, et al. Abuse potential study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) compared with immediate-release oxycodone administered orally to non-dependent, recreational opioid users. J Pain. 2014;15:S79–S79.
   Web of Science ®Google Scholar
• Setnik B, Bramson C, Sommerville K, et al. Abuse potential study of ALO-02 (extended-release oxycodone surrounding sequestered naltrexone) compared with immediate-release oxycodone and placebo when crushed and administered intranasally to non-dependent, recreational opioid users. J Pain. 2014;15:S78–S78.
   Web of Science ®Google Scholar
• Setnik B, Arora S, Drass M, et al. A multicenter, 12-month, open-label, single-arm, safety study of oxycodone hydrochloride and naltrexone hydrochloride extended-release capsules (ALO-02) in patients with moderate to severe chronic non-cancer pain. J Pain. 2013;14:S79–S79.
   PubMed Web of Science ®Google Scholar
• Coluzzi F, Mattia C. Oxycodone. Pharmacological profile and clinical data in chronic pain management. Minerva Anestesiol. 2005;71:451–460.
   PubMedGoogle Scholar
• Bostrom E, Hammarlund-Udenaes M, Us S. Blood-brain barrier transport helps to explain discrepancies in in vivo potency between oxycodone and morphine. Anesthesiology. 2008;108:495–505.
   PubMed Web of Science ®Google Scholar
• Bostrom E, Simonsson US, Hammarlund-Udenaes M. In vivo blood-brain barrier transport of oxycodone in the rat: indications for active influx and implications for pharmacokinetics/pharmacodynamics. Drug Metab Dispos. 2006;34:1624–1631.
   PubMed Web of Science ®Google Scholar
• Poyhia R, Vainio A, Kalso E. A review of oxycodone’s clinical pharmacokinetics and pharmacodynamics. J Pain Symptom Manage. 1993;8:63–67.
   PubMed Web of Science ®Google Scholar
• Nakamura A, Fujita M, Ono H, et al. G protein-gated inwardly rectifying potassium (KIR3) channels play a primary role in the antinociceptive effect of oxycodone, but not morphine, at supraspinal sites. Br J Pharmacol. 2014;171:253–264.
   PubMed Web of Science ®Google Scholar
• Zwisler ST, Enggaard TP, Mikkelsen S, et al. Impact of the CYP2D6 genotype on post-operative intravenous oxycodone analgesia. Acta Anaesthesiol Scand. 2010;54:232–240.
   PubMed Web of Science ®Google Scholar
• Gonzalez JP, Brogden RN. Naltrexone. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic efficacy in the management of opioid dependence. Drugs. 1988;35:192–213.
   PubMed Web of Science ®Google Scholar
• Porter SJ, Somogyi AA, White JM. In vivo and in vitro potency studies of 6beta-naltrexol, the major human metabolite of naltrexone. Addict Biol. 2002;7:219–225.
   PubMed Web of Science ®Google Scholar
• Porter SJ, Somogyi AA, White JM. Kinetics and inhibition of the formation of 6beta-naltrexol from naltrexone in human liver cytosol. Br J Clin Pharmacol. 2000;50:465–471.
   PubMed Web of Science ®Google Scholar
• Menelaou A, Hutchinson MR, Quinn I, et al. Quantification of the O- and N-demethylated metabolites of hydrocodone and oxycodone in human liver microsomes using liquid chromatography with ultraviolet absorbance detection. J Chromatogr B Analyt Technol Biomed Life Sci. 2003;785:81–88.
   PubMed Web of Science ®Google Scholar
• Soderberg Lofdal KC, Andersson ML, Gustafsson LL. Cytochrome P450-mediated changes in oxycodone pharmacokinetics/pharmacodynamics and their clinical implications. Drugs. 2013;73:533–543.
   PubMed Web of Science ®Google Scholar
• Rodriguez ML. Oxycodone: actions, metabolism, elimination, and detection. MLO Med Lab Obs. 2013;45:24.
   PubMedGoogle Scholar
• Korjamo T, Tolonen A, Ranta VP, et al. Metabolism of oxycodone in human hepatocytes from different age groups and prediction of hepatic plasma clearance. Front Pharmacol. 2011;2:87.
   PubMed Web of Science ®Google Scholar
• Lalovic B, Phillips B, Risler LL, et al. Quantitative contribution of CYP2D6 and CYP3A to oxycodone metabolism in human liver and intestinal microsomes. Drug Metab Dispos. 2004;32:447–454.
   PubMed Web of Science ®Google Scholar
• Poyhia R, Seppala T, Olkkola KT, et al. The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol. 1992;33:617–621.
   PubMed Web of Science ®Google Scholar
• Kirvela M, Lindgren L, Seppala T, et al. The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesth. 1996;8:13–18.
   PubMed Web of Science ®Google Scholar
• Tallgren M, Olkkola KT, Seppala T, et al. Pharmacokinetics and ventilatory effects of oxycodone before and after liver transplantation. Clin Pharmacol Ther. 1997;61:655–661.
   PubMed Web of Science ®Google Scholar
• Li Y, Sun D, Palmisano M, et al. Slow drug delivery decreased total body clearance and altered bioavailability of immediate- and controlled-release oxycodone formulations. Pharmacol Res Perspect. 2016;4:e00210.
   PubMedGoogle Scholar
• Wall ME, Brine DR, Perez-Reyes M. The metabolism of naltrexone in man. NIDA Res Monogr. 1981;28:105–131.
   PubMedGoogle Scholar
• Misra AL. Current status of preclinical research on disposition, pharmacokinetics, and metabolism of naltrexone. NIDA Res Monogr. 1981;28:132–146.
   PubMedGoogle Scholar
• Verebey K, Volavka J, Mule SJ, et al. Naltrexone: disposition, metabolism, and effects after acute and chronic dosing. Clin Pharmacol Ther. 1976;20:315–328.
   PubMed Web of Science ®Google Scholar
• Verebey K, Mule SJ. Naltrexone pharmacology, pharmacokinetics, and metabolism: current status. Am J Drug Alcohol Abuse. 1975;2:357–363.
   PubMed Web of Science ®Google Scholar
• Meyer MC, Straughn AB, Lo MW, et al. Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration. J Clin Psychiatry. 1984;45:15–19.
   PubMed Web of Science ®Google Scholar
• Colucci SV, Perrino PJ, Shram M, et al. Abuse potential of intravenous oxycodone/Naloxone solution in nondependent recreational drug users. Clin Drug Investig. 2014;34:421–429.
   PubMed Web of Science ®Google Scholar
• Wasan AD, Michna E, Edwards RR, et al. Psychiatric comorbidity is associated prospectively with diminished opioid analgesia and increased opioid misuse in patients with chronic low back pain. Anesthesiology. 2015;123:861–872.
   PubMed Web of Science ®Google Scholar
• Buckalew N, Haut MW, Aizenstein H, et al. Differences in brain structure and function in older adults with self-reported disabling and nondisabling chronic low back pain. Pain Med. 2010;11:1183–1197.
   PubMed Web of Science ®Google Scholar
• Rabey M, Slater H, O’Sullivan P, et al. Somatosensory nociceptive characteristics differentiate subgroups in people with chronic low back pain: a cluster analysis. Pain. 2015;156:1874–1884.
   PubMed Web of Science ®Google Scholar
• Coronado RA, Bialosky JE, Robinson ME, et al. Pain sensitivity subgroups in individuals with spine pain: potential relevance to short-term clinical outcome. Phys Ther. 2014;94:1111–1122.
   PubMed Web of Science ®Google Scholar
• Scholz J, Mannion RJ, Hord DE, et al. A novel tool for the assessment of pain: validation in low back pain. PLoS Med. 2009;6:e1000047.
   PubMed Web of Science ®Google Scholar
• O’Neill S, Manniche C, Graven-Nielsen T, et al. Association between a composite score of pain sensitivity and clinical parameters in low-back pain. Clin J Pain. 2014;30:831–838.
   PubMed Web of Science ®Google Scholar
• O’Neill S, Kjaer P, Graven-Nielsen T, et al. Low pressure pain thresholds are associated with, but does not predispose for, low back pain. Eur Spine J. 2011;20:2120–2125.
   PubMed Web of Science ®Google Scholar
• Yarnitsky D, Dahan A. Endogenous pain modulation: from humans to animals and back. Anesthesiology. 2015;122:734–735.
   PubMed Web of Science ®Google Scholar
• Correa JB, Costa LO, De Oliveira NT, et al. Central sensitization and changes in conditioned pain modulation in people with chronic nonspecific low back pain: a case-control study. Exp Brain Res. 2015;233:2391–2399.
   PubMed Web of Science ®Google Scholar
• Mlekusch S, Neziri AY, Limacher A, et al. Conditioned pain modulation in patients with acute and chronic low back pain. Clin J Pain. 2016;32:116–121.
   PubMed Web of Science ®Google Scholar
• Koes B. Moderate quality evidence that compared to advice to rest in bed, advice to remain active provides small improvements in pain and functional status in people with acute low back pain. Evid Based Med. 2010;15:171–172.
   PubMedGoogle Scholar
• Koes BW, Van Tulder M, Lin CW, et al. An updated overview of clinical guidelines for the management of non-specific low back pain in primary care. Eur Spine J. 2010;19:2075–2094.
   PubMed Web of Science ®Google Scholar
• Kalso E, Allan L, Dobrogowski J, et al. Do strong opioids have a role in the early management of back pain? Recommendations from a European expert panel. Curr Med Res Opin. 2005;21:1819–1828.
   PubMed Web of Science ®Google Scholar
• Gourlay D. Addiction and pain medicine. Pain Res Manag. 2005;10(Suppl A):38A–43A.
   PubMedGoogle Scholar
• Gourlay DL, Heit HA, Almahrezi A. Universal precautions in pain medicine: a rational approach to the treatment of chronic pain. Pain Med. 2005;6:107–112.
   PubMed Web of Science ®Google Scholar
• Pilgrim JL, Yafistham SP, Gaya S, et al. An update on oxycodone: lessons for death investigators in Australia. Forensic Sci Med Pathol. 2015;11:3–12.
   PubMed Web of Science ®Google Scholar
• Bannwarth B. Will abuse-deterrent formulations of opioid analgesics be successful in achieving their purpose? Drugs. 2012;72:1713–1723.
   PubMed Web of Science ®Google Scholar
• Dolgin E. TECHNOLOGY Barriers to misuse. Nature. 2015;522:S60–S61.
   PubMed Web of Science ®Google Scholar
• Ogle A, Moore K, Barrett B, et al. Clinical history and characteristics of persons with oxycodone-related deaths in Hillsborough County, Florida in 2009. Forensic Sci Int. 2012;223:47–52.
   PubMed Web of Science ®Google Scholar
• Baker DD, Jenkins AJ. A comparison of methadone, oxycodone, and hydrocodone related deaths in Northeast Ohio. J Anal Toxicol. 2008;32:165–171.
   PubMed Web of Science ®Google Scholar
• Ballantyne JC, Sullivan MD. Intensity of chronic pain - the wrong metric? New England J Med. 2015;373:2098–2099.
   PubMed Web of Science ®Google Scholar
• Butler SF. Is there support for abuse-deterrent and tamper-resistant opioid formulations? Reply to commentary. J Pain. 2013;14:361–362.
   PubMed Web of Science ®Google Scholar
• Cicero TJ, Ellis MS, Surratt HL. Effect of abuse-deterrent formulation of oxycontin. N England J Med. 2012;367:187–189.
   PubMed Web of Science ®Google Scholar
• Stahlberg H, Brett M, Schwier S, et al. Relative bioavailability of a new tamper resistant extended-release oxycodone/naloxone combination product. J Pain. 2014;15:S86–S86.
   Web of Science ®Google Scholar
• Passik SD. Tamper-resistant opioid formulations in the treatment of acute pain. Adv Ther. 2014;31:264–275.
   PubMed Web of Science ®Google Scholar
• Qi T, Wang B, Zhao SJ. The research of website tamper-resistant technology. Adv Appl Sci Manuf Pts 1 and 2. 2014;850–851:475–478.
   Google Scholar
• Poklis A. Decline in abuse of pentazocine tripelennamine (Ts and Blues) associated with the addition of naloxone to pentazocine tablets. Drug Alcohol Depend. 1984;14:135–140.
   PubMed Web of Science ®Google Scholar
• Baum C, Hsu JP, Nelson RC. The impact of the addition of naloxone on the use and abuse of pentazocine. Public Health Rep. 1987;102:426–429.
   PubMed Web of Science ®Google Scholar
• Mammen K, Bell J. The clinical efficacy and abuse potential of combination buprenorphine-naloxone in the treatment of opioid dependence. Expert Opin Pharmacother. 2009;10:2537–2544.
   PubMed Web of Science ®Google Scholar
• Butler SF, Cassidy TA, Chilcoat H, et al. Abuse rates and routes of administration of reformulated extended-release oxycodone: initial findings from a sentinel surveillance sample of individuals assessed for substance abuse treatment. J Pain. 2013;14:351–358.
   PubMed Web of Science ®Google Scholar
• Cicero TJ, Ellis MS. Abuse-deterrent formulations and the prescription opioid abuse epidemic in the united states: lessons learned from oxycontin. JAMA Psychiatry. 2015;72:424–430.
   PubMed Web of Science ®Google Scholar
• Pappagallo M, Sokolowska M. The implications of tamper-resistant formulations for opioid rotation. Postgrad Med. 2012;124:101–109.
   PubMed Web of Science ®Google Scholar
• Peniston JH. A review of pharmacotherapy for chronic low back pain with considerations for sports medicine. Phys Sportsmed. 2012;40:21–32.
   PubMed Web of Science ®Google Scholar
• Chen L, Malarick C, Seefeld L, et al. Altered quantitative sensory testing outcome in subjects with opioid therapy. Pain. 2009;143:65–70.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ahmed S, Vo T, et al. Increased pain sensitivity in chronic pain subjects on opioid therapy: a cross-sectional study using quantitative sensory testing. Pain Med. 2015;16:911–922.
   PubMed Web of Science ®Google Scholar
• Trescot AM, Helm S, Hansen H, et al. Opioids in the management of chronic non-cancer pain: an update of American Society of the Interventional Pain Physicians’ (ASIPP) Guidelines. Pain Physician. 2008;11:S5–S62.
   PubMed Web of Science ®Google Scholar
• Trescot AM, Glaser SE, Hansen H, et al. Effectiveness of opioids in the treatment of chronic non-cancer pain. Pain Physician. 2008;11:S181–200.
   PubMed Web of Science ®Google Scholar
• Bruehl S, Burns JW, Passik SD, et al. The contribution of differential opioid responsiveness to identification of opioid risk in chronic pain patients. J Pain. 2015;16:666–675.
   PubMed Web of Science ®Google Scholar
• Deyo RA, Von Korff M, Duhrkoop D. Opioids for low back pain. Bmj. 2015;350:g6380.
   PubMed Web of Science ®Google Scholar
• Breckenridge J, Clark JD. Patient characteristics associated with opioid versus nonsteroidal anti-inflammatory drug management of chronic low back pain. J Pain. 2003;4:344–350.
   PubMed Web of Science ®Google Scholar
• Volinn E, Fargo JD, Fine PG. Opioid therapy for nonspecific low back pain and the outcome of chronic work loss. Pain. 2009;142:194–201.
   PubMed Web of Science ®Google Scholar
• Martell BA, O’Connor PG, Kerns RD, et al. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction. Ann Intern Med. 2007;146:116–127.
   PubMed Web of Science ®Google Scholar
• Kobus AM, Smith DH, Morasco BJ, et al. Correlates of higher-dose opioid medication use for low back pain in primary care. J Pain. 2012;13:1131–1138.
   PubMed Web of Science ®Google Scholar
• Scherrer JF, Svrakic DM, Freedland KE, et al. Prescription opioid analgesics increase the risk of depression. J Gen Intern Med. 2014;29:491–499.
   PubMed Web of Science ®Google Scholar
• Dasgupta N, Funk MJ, Proescholdbell S, et al. Cohort study of the impact of high-dose opioid analgesics on overdose mortality. Pain Med. 2015 Sep 1. doi:10.1111/pme.12907. [Epub ahead of print]
   PubMed Web of Science ®Google Scholar
• Ilgen MA, Bohnert AS, Ganoczy D, et al. Opioid dose and risk of suicide. Pain. 2016;157:1079–1084.
   PubMed Web of Science ®Google Scholar
• Freund J, Kraus C, Hooper-Lane C. Clinical inquiry: how effective are opioids for chronic low back pain? J Fam Pract. 2015;64:584–585.
   PubMed Web of Science ®Google Scholar
• Williamson OD, Sagman D, Bruins RH, et al. Antidepressants in the treatment for chronic low back pain: questioning the validity of meta-analyses. Pain Pract. 2014;14:E33–41.
   PubMed Web of Science ®Google Scholar
• Skljarevski V, Zhang S, Desaiah D, et al. Duloxetine versus placebo in patients with chronic low back pain: a 12-week, fixed-dose, randomized, double-blind trial. J Pain. 2010;11:1282–1290.
   PubMed Web of Science ®Google Scholar
• Skljarevski V, Desaiah D, Liu-Seifert H, et al. Efficacy and safety of duloxetine in patients with chronic low back pain. Spine (Phila Pa 1976). 2010;35:E578–585.
   PubMed Web of Science ®Google Scholar
• Petzke F, Welsch P, Klose P, et al. Opioids in chronic low back pain. A systematic review and meta-analysis of efficacy, tolerability and safety in randomized placebo-controlled studies of at least 4 weeks duration. Schmerz. 2015;29:60–72.
   PubMed Web of Science ®Google Scholar
• Chaparro LE, Furlan AD, Deshpande A, et al. Opioids compared with placebo or other treatments for chronic low back pain: an update of the Cochrane review. Spine (Phila Pa 1976). 2014;39:556–563.
   PubMed Web of Science ®Google Scholar
• Chou R, Huffman LH, American Pain S, American College of P. Medications for acute and chronic low back pain: a review of the evidence for an American Pain Society/American College of Physicians clinical practice guideline. Ann Intern Med. 2007;147:505–514.
   PubMed Web of Science ®Google Scholar
• Rabey M, Poon C, Wray J, et al. Pro-nociceptive and anti-nociceptive effects of a conditioned pain modulation protocol in participants with chronic low back pain and healthy control subjects. Man Ther. 2015;20:763–768.
   PubMed Web of Science ®Google Scholar
• Yarnitsky D, Granot M, Granovsky Y. Pain modulation profile and pain therapy: between pro- and antinociception. Pain. 2014;155:663–665.
   PubMed Web of Science ®Google Scholar
• Siegenthaler A, Schliessbach J, Vuilleumier PH, et al. Linking altered central pain processing and genetic polymorphism to drug efficacy in chronic low back pain. BMC Pharmacol Toxicol. 2015;16:23.
   PubMed Web of Science ®Google Scholar