Phrenic Nerve Infiltration in Fibromyalgia

Phrenic Afferences In Organic and Metabolic Illness: Central Sensitization - Fibromyalgia

It is known that nociceptive afferences in visceral pain and visceral disorders increase sensitization in subjects suffering from fibromyalgia. These patients use to present visceral comorbidities. Those comorbidities include that of peridiaphragmatic organs, which are supplied by the phrenic nerve among other innervations. It is known that peridiaphragmatic organs trigger referred pain in the neck area, via the phrenic nerves. So, the phrenic nociceptive afferences can be contributing to enhance the state of sensitization in fibromyalgia. This study aims to analyze the ability of phrenic nerve infiltration to diminish sensitization in subjects suffering fibromyalgia, by means of a randomized controlled trial.

Study Overview

• Status: Completed
• Conditions: Fibromyalgia
• Intervention / Treatment: Other: Placebo (physiological saline serum infiltration); Drug: Bupivacain

Detailed Description

Fibromyalgia is a major problem due to issues such as the impact on quality of life and the associated health and social costs. It is characterized by a generalized state of sensitization, with a high level of perceived pain, among other features. Peripheral pain sources potentially exacerbate the central sensitization and its symptoms of chronic diffuse musculoskeletal pain and hyperalgesia. It has been shown that visceral pain enhances the level of central sensitization typical of the syndrome. So, it has been claimed that systematic assessment and treatment of visceral pain comorbidities should be a part of the management strategy in fibromyalgia.

Patients with fibromyalgia present visceral comorbidities. Those comorbidities include that of peridiaphragmatic organs, which are supplied by the phrenic nerve among other innervations. It is known that peridiaphragmatic organs trigger referred pain in the neck area, via the phrenic nerves. So, the phrenic nociceptive afferences can be contributing to enhance the state of sensitization in fibromyalgia. This study aims to analyze the ability of phrenic nerve infiltration to diminish sensitization in subjects suffering fibromyalgia.

For this purpose, the investigators intend to perform a randomized clinical trial, assessing the effects on pain threshold to pressure, visual analogue scale, range of motion and fibromyalgia specific questionnaires. There will be only one intervention session. The experimental group will receive an ultrasound-guided anaesthetic infiltration of the phrenic nerve, while the control group will receive a placebo infiltration. A one-week follow-up, with intermediate measurements, will be carried out to assess the evolution of sensitization and symptomatology.

The results of this study will make it possible to establish the role of phrenic afferences in fibromyalgia sensitization, thus making it possible to specify a specific therapeutic target (phrenic nerve) as well as the importance of visceral treatment in subjects with fibromyalgia.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41009
    • Hospitales Universitarios Virgen del Rocío y Macarena
  • Seville
    • Dos Hermanas, Seville, Spain, 41089
      • Nacho Navarro Fisioterapia
    • Lebrija, Seville, Spain, 41740
      • Asociación de Fibromialgia de Lebrija
    • Sevilla, Seville, Spain, 41018
      • Asociación de Fibromialgia de Sevilla

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women
• Over 18 and under 64 years old
• Diagnosis of Fibromyalgia
• Any peridiaphragmatic visceral disorder diagnosed by the respective specialist.
• That the subject agrees to participate in the project by signing the informed consent.

Exclusion Criteria:

• Other rheumatic diseases.
• Degenerative neurological disease.
• Major psychiatric disorder
• Cognitive deterioration
• Non-cooperative subject
• Any medical condition affecting sensory evaluation
• Contraindication to infiltration of the phrenic nerve.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phrenic nerve anesthetics infiltration; The experimental intervention will consist of ultrasound-guided anesthetic blockade of the phrenic nerve at the laterocervical supraclavicular level with 1 ml of lidocaine without vasoconstrictor 2% to infiltrate the skin and 3ml of bupivacaine without vasoconstrictor 0.25% for neural blockade, making the local anesthetic surround the nerve between the anterior scalene muscle and the sternocleidomastoid muscle.	Drug: Bupivacain; The experimental intervention will consist of ultrasound-guided anesthetic blockade of the phrenic nerve at the laterocervical supraclavicular level with 1 ml of lidocaine without vasoconstrictor 2% to infiltrate the skin and 3ml of bupivacaine without vasoconstrictor 0.25% for neural blockade, making the local anesthetic surround the nerve between the anterior scalene muscle and the sternocleidomastoid muscle.; Other Names: Bupivacaine B. Braun 2.5 mg/ml
Placebo Comparator: Physiological serum infiltration; The placebo intervention will be similar in relation to 2% lidocaine without vasoconstrictor for the skin, but an ultrasound-guided puncture will be performed at the level of the subcutaneous cellular tissue by injecting 3 ml of physiological saline.	Other: Placebo (physiological saline serum infiltration); The placebo intervention will be similar in relation to 2% lidocaine without vasoconstrictor for the skin, but an ultrasound-guided puncture will be performed at the level of the subcutaneous cellular tissue by injecting 3 ml of physiological saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Algometry	Pressure pain threshold in the specific 18 tender points in fibromyalgia. PPT levels defined as the minimum necessary pressure to evoke pain will be evaluated using a handheld electronic pressure algometer. Change from baseline in algometry.	Pre-intervention. Post-intervention: 1 hour, 3 days and 7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Improvement	Patient Global Impression of Improvement (PGI-Improvement) scale, ranging from 1 (very much better) to 7 (very much worse). It will be assessed verbally.	Pre-intervention. Post-intervention: 1 hour, 3 hours, 6 hours, 9 hours, 24 hours, 2 days, 3 days and 7 days
Numeric Pain Rating Scale	Perceived pain. Self-perceived pain intensity will be evaluated by a 0 to 10 Numeric Pain Rating Scale (NPRS), where 0 denotes no pain and 10 denotes the maximum possible pain.	Pre-intervention. Post-intervention: 1 hour, 3 hours, 6 hours, 9 hours, 24 hours, 2 days, 3 days and 7 days
Fibromyalgia Survey Questionnaire	Fibromyalgia Survey Questionnaire (Questionnaire) (parts I and III). The Fibromyalgia Survey Questionnaire will be used in the Spanish version. This questionnaire assesses the severity of fibromyalgia symptoms. The first part of this questionnaire is constituted by 3 questions related to the last week, and they have to be answered by likert scales of 3 points. Higher scores indicate higher disability. The third part of this questionnaire is constituted by a qualitative localization of pain in the last week. A higher number of body regions suffering pain constitute a worse outcome. Parts II and IV of the questionnaire will not be considered as an outcome measure since they evaluate periods of 6 months and 3 months respectively, and our post-intervention measurement will be performed just 7 days after intervention, so these parts of the questionnaire have no interest as outcome measures.	Pre-intervention. Post-intervention: 7 days.
Revised Fibromyalgia Impact Questionnaire	Revised Fibromyalgia Impact Questionnaire (Questionnaire). This questionnaire evaluates the difficulty to develop certain daily-life activities. It will be used in the Spanish version. This questionnaire assesses the severity of fibromyalgia symptoms. Scores range from 0-100 with higher scores indicating higher disability.	Pre-intervention. Post-intervention: 7 days.

Collaborators and Investigators

• Sponsor: University of Seville
• Investigators: Principal Investigator: Ángel Oliva Pascual-Vaca, Dr, University of Seville

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2023
• Primary Completion (Actual): February 19, 2024
• Study Completion (Actual): February 19, 2024

Study Registration Dates

• First Submitted: March 19, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): March 31, 2023

Study Record Updates

• Last Update Posted (Actual): February 28, 2024
• Last Update Submitted That Met QC Criteria: February 25, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Pain; Bupivacaine; phrenic nerve; anesthesia, local; anesthetics
• Additional Relevant MeSH Terms: Nervous System Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Muscular Diseases; Neuromuscular Diseases; Fibromyalgia; Myofascial Pain Syndromes; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anesthetics, Local; Bupivacaine
• Other Study ID Numbers: PAINOMICS-fibromyalgia

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