Placebo effects of a sham opioid solution: a randomized controlled study in patients with chronic low back pain

Abstract

This study tested the experimental placebo effect in a group of chronic pain patients. Forty-eight patients having chronic back pain participated in a randomized clinical trial that tested the efficacy of a sham opioid solution (NaCl) compared with an alleged neutral, completely inactive solution (NaCl). We shaped the placebo effect by 2 interventions: verbal instruction and conditioning. The patients were either told that the "solution reduces pain and improves physical capacity" or the "solution is neutral, a placebo." Half of each group was additionally conditioned (coupling solution with reduced experimental pain), yielding 4 subgroups with 12 participants each. Outcome measures were as follows: the patients' clinical back pain ratings and acute pain ratings (both examined by numerical rating scale 0-10) and self-rated functional capacity (0%-100%; time required for the exercise). Expected pain relief before and after solution intake was also assessed. The inactive solution (NaCl), when presented as an effective treatment (sham "opioid" solution), induced placebo analgesia as evident in lower ratings of the patients' clinical back pain (F(3.12,144.21) = 25.05, P < 0.001), acute pain ratings (F(1.99,87.40) = 18.12, P < 0.01), and time needed to complete a series of daily activities exercises (F(1,44) = 8.51, P < 0.01) as well as increased functional capacity (F(1,44.00) = 19.42, P < 0.001). The 2 manipulations (instruction and conditioning) changed pain expectations, and they were maintained in both sham opioid groups. The results suggest that it may be clinically useful to explicitly integrate placebo analgesia responses into pain management.

Clinical Use of Placebo Effects in Patients With Pain Disorders

“…Laboratory studies showed that patients with chronic Irritable Bowel Syndrome (Kaptchuk et al, 2008; Vase, Robinson, Verne, & Price, 2003, 2005), idiopathic and neuropathic pain (Petersen et al, 2014, 2012; Vase, Petersen, & Lund, 2014), and low back pain (Carvalho et al, 2016; Hashmi et al, 2012; Klinger, Kothe, Schmitz, Kamping, & Flor, 2017), show robust placebo hypoalgesic responses.…”

“…Moreover, analgesic placebos can lead to excellent clinical results for patients with chronic pain (Carvalho et al, 2016; Klinger et al, 2017), idiopathic and neuropathic pain (Petersen et al, 2014, 2012; Vase et al, 2014), migraine (Kam-Hansen et al, 2014), and knee osteoarthritis (Gollub et al, 2018; Tetreault et al, 2016). Therefore, why should analgesic placebos not be used in daily clinical practice?…”

“…Fourth, Klinger et al (2017) were able to reduce experimental and clinical pain and to improve the patients’ physical capacity in a sample of 48 patients suffering from chronic back pain. These results were generated by using a placebo tincture combined with the instruction that the tincture is a “highly effective opioid” and provided additional conditioning.…”

The Placebo Phenomenon: A Narrow Focus on Psychological Models

“…Moreover, some learning processes may occur independently of conditioning by means of vicarious observation, social learning, or verbal communication (Kirsch 1985, 1997, 2004). Given that placebo effects have been demonstrated to be influenced by verbal suggestions, conditioning processes, social observation, personality factors, and genetics, the underlying endogenous mechanisms mediating the processing of the vast amount of information within a clinical environment are far more integrated and complex than one single process alone (Bartels et al 2014; Benedetti et al 2003; Brody and Brody 2000; Colagiuri et al 2015; Colloca and Benedetti 2006, 2009; Colloca and Grillon 2014; Corsi and Colloca 2017; Darragh et al 2015; Hall, Loscalzo, and Kaptchuk 2015; Kirsch 2004; Klinger et al 2017b; van Laarhoven et al 2011; Vase et al 2003; Vogtle, Barke, and Kroner-Herwig 2013; Wang et al. 2017).…”

Sham opioids relieve multidimensional aspects of chronic back pain

“…via instructions) and reinforced expectations (e.g. via exposure to a pain reduction using a behavioral conditioning manipulation) would affect not only the perception of experimental acute pain intensity but also pre-existing clinical pain, as well as back pain-related behaviors and functional capacity in patients with history of chronic back pain [9]. An inactive solution (NaCl) was presented as an effective treatment (sham “opioid” solution) to chronic back pain patients.…”