Effect of Treatment Expectation on Placebo Response and Analgesic Efficacy

Sanders, Anne E.; Slade, Gary D.; Fillingim, Roger B.; Ohrbach, Richard; Arbes, Samuel J.; Tchivileva, Inna E.

doi:10.1001/jamanetworkopen.2020.2907

Cited by 15 publications

(16 citation statements)

References 6 publications

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“…Propranolol treatment did not result in a significant or clinically meaningful improvement in TMD‐related pain when compared with placebo. However, there was a larger than expected placebo effect on TMD‐related pain, which was subsequently revealed to be related to increased expectation of analgesia in patients with the most tender masseter muscles 34 . A greater percentage of patients did achieve a 30% or 50% reduction in average weekly pain intensity with propranolol treatment than with placebo, and there was a significant improvement in pain‐free jaw opening in the propranolol group 33 .…”

Section: Pharmacological Evidencementioning

confidence: 92%

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

Cairns

2022

J of Oral Rehabilitation

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Background Temporomandibular disorders (TMD) are diagnosed based on symptom presentation and, like other functional pain disorders, often lack definitive pathology. There is a strong association between elevated stress levels and the severity of TMD‐related pain, which suggests that alterations in autonomic tone may contribute to this pain condition. Objectives This narrative review examines the association between altered autonomic function and pain in TMD. Methods Relevant articles were identified by searching PubMed and through the reference list of those studies. Results TMD sufferers report an increased incidence of orthostatic hypotension. As in other chronic musculoskeletal pain conditions, TMD is associated with increased sympathetic tone, diminished baroreceptor reflex sensitivity and decreased parasympathetic tone. It remains to be determined whether ongoing pain drives these autonomic changes and/or is exacerbated by them. To examine whether increased sympathetic tone contributes to TMD‐related pain through β2 adrenergic receptor activation, clinical trials with the beta blocker propranolol have been undertaken. Although evidence from small studies suggested propranolol reduced TMD‐related pain, a larger clinical trial did not find a significant effect of propranolol treatment. This is consistent with human experimental pain studies that were unable to demonstrate an effect of β2 adrenergic receptor activation or inhibition on masticatory muscle pain. In preclinical models of temporomandibular joint arthritis, β2 adrenergic receptor activation appears to contribute to inflammation and nociception, whereas in masticatory muscle, α1 adrenergic receptor activation has been found to induce mechanical sensitisation. Some agents used to treat TMD, such as botulinum neurotoxin A, antidepressants and α2 adrenergic receptor agonists, may interact with the autonomic nervous system as part of their analgesic mechanism. Conclusion Even if dysautonomia turns out to be a consequence rather than a causative factor of painful TMD, the study of its role has opened up a greater understanding of the pathogenesis of this condition.

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Section: Pharmacological Evidencementioning

confidence: 92%

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

Cairns

2022

J of Oral Rehabilitation

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“…Additionally, it could make the parents/tutors more likely to report a positive outcome. What is more, before the treatment, patients generally could already be perceived as very hopeful, possibly because the study center has been involved in research on this issue for years, with hundreds of cases treated in the region, which could favor the placebo effect [ 59 ]. To this effect, the aforementioned recall bias [ 51 ] can be added, which hypothetically would overestimate the number of episodes in the previous years, while those in the following year would be better quantified by monthly follow-up calls.…”

Section: Discussionmentioning

confidence: 99%

Effects of Osteopathic T9–T10 Vertebral Manipulation in Tonsillitis: A Randomized Clinical Trial

et al. 2021

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This study aimed to determine whether osteopathic manipulation of the T9–T10 vertebrae improves the evolution of tonsillitis. A randomized, stratified, controlled clinical trial with blinded patients, evaluator and data analyst was performed. The patients in the control group (CG) underwent a “sham” manipulation. A high-speed, low-amplitude technique was applied to the T9–T10 vertebrae in the osteopathic manipulative group (OMG) patients. The number of days needed to resolve the tonsillitis was significantly lower (p = 0.025) in the OMG (2.03 ± 0.95 days) than the CG (2.39 ± 0.82 days). Additionally, the number of episodes of tonsillitis after the treatment decreased significantly more in the OMG (0.8 ± 1.88 episodes/year in total) than the CG (2 ± 2.12) (p = 0.005). In the OMG, 60.8% had no recurrences of tonsillitis, compared to 22.5% of the CG, in the following year (χ2 (1) = 15.57, p < 0.001). No patients reported adverse effects. It has been concluded that during an episode of tonsillitis, the number of days to resolution was significantly lower after the application of an osteopathic manipulation of the T9–T10 vertebrae, compared to a sham manipulation. The number of subsequent year tonsillitis episodes was greatly reduced in both groups, significantly more in the OMG than in the CG patients.

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“…Since 81% of the patients already received local exercise therapy in the past, this might have resulted in a lack of motivation for this study. Future studies should therefore include a control group receiving sham manipulations to elucidate factors related to the placebo effect, like patient expectations of pain relief or treatment motivation [ 53 ]. Therefore, our results obtained in this relatively small convenience sample ( n = 43) should not be extrapolated to the entire PFPS population.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of local exercise therapy versus spinal manual therapy in patients with patellofemoral pain syndrome: medium term follow-up results of a randomized controlled trial

Scafoglieri

Broeck

Willems

et al. 2021

BMC Musculoskelet Disord

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Background Increasing evidence has shown benefits of spinal manipulations in patients with patellofemoral pain syndrome (PFPS). There is scarcity regarding medium term effects of spinal manual therapy on outcome measures in PFPS patients. Therefore, the aim of the present study was to compare the effectiveness of local exercise therapy and spinal manual therapy for knee pain, function and maximum voluntary peak force (MVPF) velocity of the quadriceps in PFPS patients. Methods Forty-three patients with PFPS were randomly assigned to a local exercise or spinal manual therapy group. The local exercise group received six sessions (one session per week) of supervised training of the knee-and hip muscles with mobilization of the patellofemoral joint. The spinal manual therapy group received six interventions (one intervention per week) of high velocity low thrust manipulations at the thoracolumbar region, sacroiliac joint, and/or hip. All patients were also asked to do home exercises. Maximum, minimum and current pain were measured using the visual analogue scale. Function was assessed with the anterior knee pain scale (AKPS) and MPFV was recorded using a Biodex System 3 dynamometer. Patients were assessed before intervention, after 6 weeks of intervention and after 6 weeks of follow-up. Between-group differences at assessments were analysed by way of analysis of covariance with Bonferroni correction. Results Pain and functionality improved more following spinal manipulative therapy than local exercise therapy. After 6 weeks of intervention the between-group difference (local versus spinal) for maximal pain was 23.4 mm [95% CI: 9.3, 37.6; effect size (ES): 1.04] and − 12.4 [95% CI: − 20.2, − 4.7; ES: 1.00] for the AKPS. At 6 weeks of follow-up the between-group difference for maximal pain was 18.7 mm [95% CI: 1.4, 36.0; ES: 0.68] and − 11.5 [95% CI: − 19.9, − 3.3; ES: − 0.87] for the AKPS. Conclusions This study suggests that spinal manual therapy is more effective than local exercise therapy in improving pain and function in patients with PFPS in the medium term. We suggest for future research to investigate whether combining local exercise therapy and spinal manual therapy is more effective than either single intervention on its own. This clinical trial study was approved by the Medical Ethics Committee METC Z under registration number NL57207.096. and registered retrospectively in ClinicalTrials.gov PRS with registration ID number NCT04748692 on the 10th of February 2021.

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Effect of Treatment Expectation on Placebo Response and Analgesic Efficacy

Abstract: Dr Slade had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Cited by 15 publications

References 6 publications

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

The contribution of autonomic mechanisms to pain in temporomandibular disorders: A narrative review

Effects of Osteopathic T9–T10 Vertebral Manipulation in Tonsillitis: A Randomized Clinical Trial

Effectiveness of local exercise therapy versus spinal manual therapy in patients with patellofemoral pain syndrome: medium term follow-up results of a randomized controlled trial

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