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

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.

Study Overview

• Status: Completed
• Conditions: Communication
• Intervention / Treatment: Behavioral: Placebo and Nocebo effect

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur
    • Cheras, Kuala Lumpur, Malaysia, 56000
      • Hospital Canselor Tuanku Muhriz,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Nocebo; 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; Positive suggestion and words is used on Placebo group Negative suggestion and words is used on Nocebo group
Placebo Comparator: Placebo; 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; Positive suggestion and words is used on Placebo group Negative suggestion and words is used on Nocebo group

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universiti Kebangsaan Malaysia Medical Centre

Publications and helpful links

General Publications

• Mohd Fahmi Z, Lai LL, Loh PS. Validation of the Malay version of the Amsterdam Preoperative Anxiety and Information Scale (APAIS). Med J Malaysia. 2015 Aug;70(4):243-8.
• Varelmann D, Pancaro C, Cappiello EC, Camann WR. Nocebo-induced hyperalgesia during local anesthetic injection. Anesth Analg. 2010 Mar 1;110(3):868-70. doi: 10.1213/ANE.0b013e3181cc5727. Epub 2009 Dec 30.
• Moerman N, van Dam FS, Muller MJ, Oosting H. The Amsterdam Preoperative Anxiety and Information Scale (APAIS). Anesth Analg. 1996 Mar;82(3):445-51. doi: 10.1097/00000539-199603000-00002.
• Dutt-Gupta J, Bown T, Cyna AM. Effect of communication on pain during intravenous cannulation: a randomized controlled trial. Br J Anaesth. 2007 Dec;99(6):871-5. doi: 10.1093/bja/aem308. Epub 2007 Oct 30.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2020
• Primary Completion (Actual): May 21, 2021
• Study Completion (Actual): May 28, 2021

Study Registration Dates

• First Submitted: July 2, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2023
• Last Update Submitted That Met QC Criteria: May 18, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Pain; Anxiety; Placebo; Nocebo; Local Skin Infiltration
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: UKM PPl/111/8/JEP-2020-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No