Pain Response to Open Label Placebo in Induced Acute Pain in Healthy Adult Males

Abstract

Background Open label placebos with patient education are effective in reducing chronic pain, and recent studies on their effect on pain have established interest in this field. Nevertheless, data on their effect on acute pain are scarce, and on hyperalgesia and allodynia, absent. This study assessed the effect of open label placebos on acute pain in healthy adult males and the influence of placebo education. Methods Thirty-two healthy males were included in this prospective, randomized, assessor-blinded crossover, single-center study assessing pain intensities (via numeric rating scale), area of hyperalgesia (von Frey filament), and allodynia (dry cotton swab) in a pain model utilizing intracutaneous electrical stimulation. The authors compared the effect of intravenous open label placebo on pain compared to no treatment. The authors further examined the effect of placebo on hyperalgesia and allodynia, and the influence of education (short vs. detailed) before placebo application. Saliva cortisol concentrations were also measured. Results Pain ratings (median, first to third quartile) were 21% lower during placebo treatment compared to no treatment, 4.0 (3.2 to 4.9) versus 5.1 (4.7 to 5.4), respectively (P = 0.001). The areas of hyperalgesia and allodynia were lower during placebo treatment compared to no treatment (hyperalgesia, 30 cm2 [17 to 47] vs. 55 cm2 [42 to 68], P = 0.003; allodynia, 24 cm2 [11 to 39] vs. 45 cm2 [31 to 62], P = 0.007). This corresponds to reductions of 47%. The extent of placebo education had no effect on pain. Saliva cortisol decreased significantly over time and was under the limit of detectability in the majority of participants in postbaseline measurements in both treatment branches. Baseline cortisol was not associated with the placebo effect or strength applied of current to reach defined pain ratings. Conclusions Open label placebos might play a role in multimodal analgesic concepts. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Open-Label Placebo Treatment for Acute Postoperative Pain (OLP-POP Study): Study Protocol of a Randomized Controlled Trial

“…Evidence on OLP effects in acute pain on the other hand is limited, yet promising: Findings of two studies investigating the potential of Conditioned OLP (COLP) to reduce pain intensity and opioid dose in patients with spinal cord injury/polytrauma (30) and following spine surgery (31) suggest that COLP might also be effective in acute pain by showing reductions of opioid doses compared to Treatment As Usual (TAU). These results are supported by the findings of several experimental OLP analgesia studies in healthy populations (7,8,(32)(33)(34). However, there is lack of investigations of unconditioned OLP in acute pain.…”

“…On the other hand, there have also been investigations showing no additional improvement when a treatment rationale was delivered alongside placebo administration: For example, allergic symptoms were similarly reduced even when pills were given without further explanation (19). In line, our recent study on OLP analgesia in healthy male adults (32) showed a comparable effect on pain reduction in both a short education group as well as in a detailed education group. This result is of great importance, because the possibility of providing OLPs with a short education makes them feasible in clinical practice.…”

“…OLPs have been shown to be effective in some clinical populations [see (11,12) for an overview], e.g., in chronic low back pain (13,(15)(16)(17). In addition, there are promising results by several experimental OLP analgesia studies (7,8,(32)(33)(34). However, concerning OLP effects in acute pain, there is only limited evidence.…”

Blinding, sham, and treatment effects in randomized controlled trials for back pain in 2000–2019: A review and meta-analytic approach

“…Our finding may add more support to accumulating evidence toward potential benefits of placebo and sham treatments with complexity in research and clinical contexts/settings. 57,58…”

“…Our finding may add more support to accumulating evidence toward potential benefits of placebo and sham treatments with complexity in research and clinical contexts/settings. 57,58 Second, our study conveys some methodologic strengths: back pain is an ideal medical condition to study our aims because multiple treatment modalities are available, which made a comparative review possible. Third, we used standardized and validated metrics for quantifying the blinding (blinding index) and treatment effects (effect sizes).…”