Understanding Rebound Pain After Regional Anesthesia Resolution in Healthy Volunteers

Understanding Rebound Pain After Regional Anesthesia Resolution: Mechanistic Trial in Healthy Volunteers

Regional anesthesia decreases postoperative pain scores and opioid consumption, and may prevent chronic pain after surgery in patients undergoing surgery. However, some patients experience an increase of pain into the severe range when the nerve block wears off, also known as rebound pain. The investigators are studying if a nerve block (numbing injection) in the arm causes hyperalgesia (increased pain) when the nerve block is wearing off.

Study Overview

• Status: Completed
• Conditions: Healthy; Pain, Acute; Regional Anesthesia Morbidity
• Intervention / Treatment: Drug: Mepivacaine

Detailed Description

This is a prospective, randomized study in healthy volunteers who will undergo sensory testing using quantitative sensory testing (QST), complete psychosocial and pain questionnaires, and ultrasound-guided peripheral nerve block of the arm (axillary nerve block) in a supervised, monitored setting (BWH Clinical Investigation Center). The investigators plan to assess the association between different QST modalities at different time points pre- and post-nerve block resolution. Semi-structured interviews and qualitative analysis will be used to explore patient's experiences with nerve block placement.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age ≥ 18 years old, ≤ 65 years old
• BMI >18, < 35
• Able to speak and understand English
• Willingness to undergo psychophysical testing (e.g., QST, pain questionnaires)
• Willingness to have nerve block performed

Exclusion Criteria:

• Ongoing acute or chronic pain in upper extremities
• Skin or tissue infection affecting upper extremities
• Previous hypersensitivity to mepivacaine or lidocaine
• Previous neuropathy (numbness, paresthesia, or motor weakness) in either upper extremity
• Loss of any limb
• Bleeding issues or bleeding disorder
• History of alcohol or drug abuse
• Currently pregnant or breastfeeding
• History of seizure or epilepsy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Block upper extremity (arm); Upper extremity with a nerve block	Drug: Mepivacaine; Injection of 1.5% Mepivacaine in nerve block; Other Names: Prilocaine
No Intervention: Control upper extremity (arm); Upper extremity without a nerve block

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heat pain detection threshold at time 1 hr	Heat pain detection threshold (°C) between block arm and control arm using a heat probe at 1 hour after nerve block resolution	1 hour after nerve block resolution

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heat pain detection threshold and tolerance	Heat pain detection threshold and tolerance (°C) between block arm and control arm using a heat probe at different time points up to 3 hours nerve block resolution	0-3 hours after nerve block resolution
Pressure pain threshold and tolerance	Pressure pain threshold and tolerance (N of force) between block arm and control arm using an algometer at different time points up to 3 hours nerve block resolution	0-3 hours after nerve block resolution
Temporal summation and sharp pain	Temporal summation and sharp pain (evaluated by numerical rating scale 0-10 pain score) between block arm and control arm using a pinprick device at different time points up to 3 hours nerve block	0-3 hours after nerve block resolution
Light touch detection	Light touch detection (mN of force) between block arm and control arm using von Frey filaments at different time points up to 3 hours nerve block	0-3 hours after nerve block resolution
Light touch pain threshold	Light touch pain threshold (mN of force) between block arm and control arm using von Frey filaments at different time points up to 3 hours nerve block	0-3 hours after nerve block resolution

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temperature change	To observe the change in temperature between block arm and control arm (°C) pre, during, and post nerve block	6-8 hours
Patient's experiences with nerve block	Semi-structured interviews will be used to explore patient's experiences with nerve block placement using an immersion/crystallization approach to identify emergent themes	6-8 hours
Pain catastrophizing and gender differences	Correlation between situational pain catastrophizing (0-24 scale) and gender	6-8 hours

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Yun-Yun K Chen, MD, Brigham and Women's Hospital

Publications and helpful links

Helpful Links

• Mass General Brigham Rally Flyer

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2023
• Primary Completion (Actual): May 28, 2024
• Study Completion (Actual): May 28, 2024

Study Registration Dates

• First Submitted: July 16, 2023
• First Submitted That Met QC Criteria: August 17, 2023
• First Posted (Actual): August 22, 2023

Study Record Updates

• Last Update Posted (Estimated): November 5, 2025
• Last Update Submitted That Met QC Criteria: November 4, 2025
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Regional anesthesia; Healthy volunteer; Rebound pain
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Acute Pain; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Anilides; Amides; Aniline Compounds; Amines; Piperidines; Prilocaine; Mepivacaine
• Other Study ID Numbers: 2023P001767

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes