A comparative evaluation of placebo effect on pain perception parameters in open-label versus double-blind groups: a prospective randomized pilot study in healthy volunteers
DOI:
https://doi.org/10.18203/2319-2003.ijbcp20231115Keywords:
Open-label placebo, Double-blind placebo, Pain perceptionAbstract
Background: Considerable placebo response rate is commonly observed in placebo-controlled trials involving analgesics. However, there is paucity of evidence with regard to comparison of effect of open-label placebo versus double-blind placebo on pain perception.
Methods: In this study, cold water maintained at 4±1°C was used to induce experimental pain. Enrolled subjects were randomized to receive either 2% lignocaine gel as active drug or K-Y jelly as placebo as per the groups in open-label (two groups) and double-blind (two groups) study. Pain perception was evaluated using pain threshold time and pain tolerance time after immersion of subject’s hand in the cold water. Pain intensity was assessed using visual analogue scale (VAS).
Results: Sixty-nine subjects were randomized into 4 study groups namely open-label lignocaine (OLL; N=17), open-label placebo (OLP; N=18), double-blind lignocaine (DBL; N=17) and double-blind placebo (DBP; N=17). OLP application increased pain intensity on VAS from 67 (47, 84) to 72 (39, 88) mm (p=0.018). OLL application reduced pain perception pain threshold time from 20.4 (4.0, 45.1) to 24.1 (6.3, 124.2) seconds (p=0.049) and pain tolerance time from 32.7 (6.8, 110.2) to 40.0 (7.7, 156.7) seconds (p=0.019). The change in pain parameters (before and after application of study intervention) was comparable without any significant difference among the four study groups (p=0.257 for pain threshold time, p=0.165 for pain tolerance time and p=0.563 for pain intensity score).
Conclusions: Lignocaine and placebo gel application showed comparable change in pain perception irrespective of blinding.
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References
Kaptchuk TJ, Friedlander E, Kelley JM, Sanchez MN, Kokkotou E, Singer JP, et al. Placebos without deception: a randomized controlled trial in irritable bowel syndrome. PLoS One. 2010;5(12):e15591.
Bendtsen L, Mattsson P, Zwart JA, Lipton RB. Placebo response in clinical randomized trials of analgesics in migraine. Cephalalgia. 2003;23(7):487-90.
Häuser W, Bartram-Wunn E, Bartram C, Tölle TR. Placebo responders in randomized controlled drug trials of fibromyalgia syndrome: Systematic review and meta-analysis. Schmerz. 2011;25(6):619-31.
Castelnuovo G, Giusti EM, Manzoni GM, Saviola D, Gabrielli S, Lacerenza M, et al. What is the role of the placebo effect for pain relief in neurorehabilitation? clinical implications from the italian consensus conference on pain in neurorehabilitation. Front Neurol. 2018;9:310.
Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain. 2016;157(12):2766-72.
Kelley JM, Kaptchuk TJ, Cusin C, Lipkin S, Fava M. Open-label placebo for major depressive disorder: a pilot randomized controlled trial. Psychother Psychosom. 2012;81(5):312-4.
Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, et al. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med. 2014;6(218):218.
Lembo A, Kelley JM, Nee J, Ballou S, Iturrino J, Cheng V, et al. Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial. Pain. 2021;162(9):2428-35.
Oertel BG, Lötsch J. Clinical pharmacology of analgesics assessed with human experimental pain models: bridging basic and clinical research. Br J Pharmacol. 2013;168(3):534-53.
Reddy KS, Rani PU, Naidu MU, Rao TR. A simple cold pressure technique for the evaluation of analgesic drugs in healthy subjects. Indian J Pharmacol. 2012; 44(5):571-5.
Birnie KA, Petter M, Boerner KE, Noel M, Chambers CT. Contemporary use of the cold pressor task in pediatric pain research: a systematic review of methods. J Pain. 2012;13(9):817-26.
Mitchell LA, MacDonald RA, Brodie EE. Temperature and the cold pressor test. J Pain. 2004;5(4):233-7.
Zheng B, Ren M, Lin F, Yao L. Prediction of pain in orthodontic patients based on preoperative pain assessment. Patient Prefer Adhere. 2016;10:251-6.
Mourot L, Bouhaddi M, Regnard J. Effects of the cold pressor test on cardiac autonomic control in normal subjects. Physiol Res. 2009;58(1):83-91.
Carlino E, Piedimonte A, Benedetti F. Nature of the placebo and nocebo effect in relation to functional neurologic disorders. Handb Clin Neurol. 2016;139: 597-606.
von Wernsdorff M, Loef M, Tuschen-Caffier B, Schmidt S. Effects of open-label placebos in clinical trials: a systematic review and meta-analysis. Sci Rep. 2021;11(1):3855.
Silverthorn DU, Michael J. Cold stress and the cold pressor test. Adv Physiol Educ. 2013;37(1):93-6.
Nouwen A, Cloutier C, Kappas A, Warbrick T, Sheffield D. Effects of focusing and distraction on cold pressor-induced pain in chronic back pain patients and control subjects. J Pain. 2006;7(1):62-71.
MacLachlan C, Shipton EA, Wells JE. The Cold Pressor Test as a Predictor of Prolonged Postoperative Pain, a Prospective Cohort Study. Pain Ther. 2016; 5(2):203-13.
Lor YC, Shih PC, Chen HH, Liu SJ, Chao HC, Hwang LC, et al. The application of lidocaine to alleviate the discomfort of nasogastric tube insertion: A systematic review and meta-analysis. Medicine. 2018;97(5): e9746.
Derry S, Wiffen PJ, Kalso EA, Bell RF, Aldington D, Phillips T, et al. Topical analgesics for acute and chronic pain in adults - an overview of Cochrane Reviews. Cochrane Database Syst Rev. 2017;5(5): 8609.
Schneider T, Luethi J, Mauermann E, Bandschapp O, Ruppen W. Pain response to open label placebo in induced acute pain in healthy adult males. Anesthesiology. 2020;132(3):571-80.
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