Positive Treatment Expectancies Reduce Clinical Pain and Perceived Limitations in Movement Ability Despite Increased Experimental Pain: A Randomized Controlled Trial on Sham Opioid Infusion in Patients with Chronic Back Pain

Abstract

<b><i>Background:</i></b> Increasing evidence for the efficacy of analgesic placebo effects in laboratory studies with healthy persons raises the question whether placebos could be used to improve the treatment of pain patients. Expectancies play a central role in shaping analgesic placebo but also nocebo effects. <b><i>Objectives:</i></b> We investigated to what extent a sham opioid infusion (saline solution) produces sustained clinically relevant placebo and nocebo effects in chronic back pain patients. <b><i>Methods:</i></b> Fifty-nine patients received the sham opioid infusion applied via a large drain dressing and were compared to 14 control patients without intervention (natural history, NH) while experimental pain stimuli were applied. All subjects were told that the infusion would decrease pain although in rare cases pain increase would be possible (induction of expectancy). In addition, conditioning was introduced where the participants either experienced a decrease in experimental pain (<i>n</i> = 17; placebo conditioning), an increase (<i>n</i> = 21; nocebo conditioning), or no change (<i>n</i> = 21, no conditioning). <b><i>Results:</i></b> Compared to the NH group, all infusion groups showed positive treatment expectancies and significantly (<i>p</i> < 0.001) reduced clinical back pain (primary outcome) and pain-related disability (secondary outcome, assessed by self-reported functional capacity and perceived impairment of mobility). Even the nocebo conditioned group experiencing increased experimental pain developed positive treatment expectancies followed by reduced pain experience. Positive treatment expectancies and relief in clinical back pain were significantly positively correlated (<i>r</i> = 0.72, <i>p</i> < 0.01). <b><i>Conclusions:</i></b> These findings suggest that it may be beneficial to explicitly shape and integrate treatment expectancies into clinical pain management.

Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants

“…First, although expectation ratings were larger in the TMD patients than in the controls, they did not predict placebo effects, contrary to prior studies [for a review, see 39] and this may have depended on the experimental setting. Second, we did not include a group with no conditioning [for an example, see 19], limiting the generalizability of these results to verbally induced placebo effects. Third, we used conditioning strengths to simulate prior therapeutic experiences similarly to a previous study [52].…”

“…We used a pain model to explore how expectations shape placebo effects in healthy controls and in a target population of temporomandibular disorder (TMD), a chronic pain condition that occurs in 5-10% of the general population [5][6][7][8][9][10]. Prior studies on placebo effects have been conducted with both behavioral and/or biological approaches in chronic irritable bowel syndrome [11][12][13], idiopathic and neuropathic pain [14][15][16], low back pain [17][18][19], migraine [20], and knee osteoarthritis [21]. Very often, these studies lack comparison with healthy participants, although a recent meta-analysis reported a greater benefit from placebo treatment in patients than in healthy participants [22].…”

What Should Clinicians Tell Patients about Placebo and Nocebo Effects? Practical Considerations Based on Expert Consensus

“…Placebo and nocebo effects can substantially modulate the efficacy and tolerability of medical and psychological interventions for many symptoms and conditions [1][2][3]. Placebo and nocebo effects refer to favorable or adverse effects, respectively, that can arise as part of an active or inert intervention due to factors such as what the patient expects, the patient-clinician relationship, and other contextual factors [4][5][6][7][8][9]. These effects can be clinically meaningful, with effect sizes for some conditions approaching treatment effect sizes [10].…”

Klinische Aspekte von Placebo

“…Die einer Placeboreaktion zugrundeliegenden Mechanismen sind bis heute nicht endgültig geklärt. Eine zentrale Rolledies gilt insbesondere für die analgetische Placeboreaktionspielt die Erwartung des Patienten im Hinblick auf die Behandlung [12,13]. Positive Erwartungseffekte zeigen sich in subjektiven Angaben wie z.…”

“…Schmerztherapie Bei einer Schmerztherapie ist davon auszugehen, dass die Erwartung des Patienten mit der Placeboreaktion korreliert [12]. Je positiver also die Erwartung an das Placebo ist, desto größer ist auch die Placeboreaktion "Schmerzlinderung".…”