Placebo Versus Nocebo: Effects on Pain and Anxiety During Local Anaesthetic Infiltration in Parturient Undergoing Elective Caesarean Delivery

Study Overview
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Brief Summary
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This randomized trial compared placebo and nocebo effect over anaesthetist-patient communication on pain and anxiety score during local anaesthetic (LA) skin infiltration in parturient undergoing caesarean delivery under regional anaesthesia (RA). A secondary objective was to determine if education level and previous RA experience affect pain and anxiety scores. Parturients scheduled for elective caesarean delivery were randomised into Placebo (P) or Nocebo (N) group. Baseline Amsterdam Preoperative Anxiety & Information Scale (APAIS0) were obtained. Standardised scripts describing the LA skin infiltration for RA were used during the pre-anaesthetic review. (N) group were explained with words like pain, prick, sharp while words like numb, comfort, tolerable were used in the (P) group, avoiding painful expressions. The same scripts will be repeated before skin infiltration during the RA procedure. On the day of surgery, a second (APAIS1) was obtained upon arrival to the theatre. Pain score using the numerical rating scale (NRS) was assessed after LA infiltration.

Detailed Description
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We randomised participants into either the nocebo (N) or placebo (P) group. We obtained a baseline anxiety score (APAIS0) using the Amsterdam Preoperative Anxiety and Information Scale (APAIS) during the pre-anaesthesia visit. Following that, we informed subjects in the N group a negative suggestion, using the following script: During the local anaesthetic injection, you are going to feel a sharp prick at your back; this is usually the most painful part of the procedure. On the other hand, we used a positive suggestion on the P group: We will administer some local anaesthetic to numb your back; this will allow the procedure to be more comfortable and tolerable for you. We obtain a second anxiety score (APAIS1) in the operating theatre before the caesarean section. We carried out either spinal anaesthesia or continuous spinal epidural according to standard hospital protocol and indication. Before the LA skin infiltration, the anaesthetist repeats the same script to the subjects according to the prior randomisation. Five millilitres of lignocaine 2% is injected intradermally and subcutaneously by the anaesthetist into interspinous space in a single pass through a 22-gauge needle to create a skin wheal. During the LA infiltration, only the attending anaesthetist performing the procedure gave participants verbal instructions; other personnel remained silent throughout. We recorded the presence of vocalisation of pain, withdrawal movement or facial grimacing. Immediately after the LA infiltration, a blinded and trained general anaesthetic nurse or personnel enters the operating theatre to assess the subjects' pain score using the numerical rating scale (NRS). After collection of the pain score, the anaesthetist performed the remaining anaesthetic procedure as per clinical routine.

Official Title
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Placebo Versus Nocebo: Effects on Pain and Anxiety During Local Anaesthetic Infiltration in Parturient Undergoing Elective Caesarean Delivery

Conditions
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Communication

Intervention / Treatment
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* Behavioral: Placebo and Nocebo effect


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: American Society of Anaesthesiology (ASA) II category parturient listed for elective caesarean delivery. Can understand intended verbal communication Exclusion Criteria: receiving any form of analgesia within 6 hours before the study chronic pain, anxiety disorders allergy to Local Anaesthetic drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: We randomised participants into either the nocebo (N) or placebo (P) group using computer generated numbers
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nocebo<br>We informed subjects in the N group a negative suggestion, using the following script: During the local anaesthetic injection, you are going to feel a sharp prick at your back; this is usually the painful part of the procedure | Behavioral: Placebo and Nocebo effect<br>* Positive suggestion and words is used on Placebo group Negative suggestion and words is used on Nocebo group<br>|
| Placebo Comparator: Placebo<br>We informed subjects in the P group a positive suggestion, using the following script: We will administer some local anaesthetic to numb your back; this will allow the procedure to be more comfortable and tolerable for you. | Behavioral: Placebo and Nocebo effect<br>* Positive suggestion and words is used on Placebo group Negative suggestion and words is used on Nocebo group<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain score | Pain score during local anaesthetic infiltration using Numerical Rating Scale (NRS) (range 0-10) where 0 is no pain at all and 10 is  worst pain ever felt | Throughout study completion, average of 10 months | 
| Baseline anxiety score | Validated questionnare using the Amsterdam Preoperative Anxiety & Information Scale. (APAIS) (Range 6-30). Higher scores mean higher anxiety level | Through study completion, average of 10 months | 
| Preoperative anxiety score | Validated questionnare using the Amsterdam Preoperative Anxiety & Information Scale. (Range 6-30). Higher scores mean higher anxiety level | Through study completion, average of 10 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association of Education level on Pain and anxiety score | Correlation between subjects education level on pain score (NRS) and anxiety score (APAIS) | Through study completion, average of 10 months | 
| Association of past history of regional anesthesia on Pain and anxiety score | Correlation between subjects previous experience of regional anesthesia on pain score (NRS) and anxiety score (APAIS) | Through study completion, average of 10 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Local Skin Infiltration, Placebo, Nocebo, Pain, Anxiety