Identification of MOR-Positive B Cell as Possible Innovative Biomarker (Mu Lympho-Marker) for Chronic Pain Diagnosis in Patients with Fibromyalgia and Osteoarthritis Diseases.

Vincenzo Mollace,Michael Tenti,Laura Vitiello,Sara Ilari,Chiara Gioia,Paola Gremigni,Antonello Bonci,Valentina Malafoglia,William Raffaeli,Cristina Iannuccelli,Carlo Tomino,Carolina Muscoli,Manuela Di Franco

doi:10.3390/ijms21041499

Abstract

Fibromyalgia (FM) diagnosis follows the American College of Rheumatology (ACR) criteria, based on clinical evaluation and written questionnaires without any objective diagnostic tool. The lack of specific biomarkers is a tragic aspect for FM and chronic pain diseases in general. Interestingly, the endogenous opioid system is close to the immune one because of the expression of opioid receptors on lymphocytes membrane. Here we analyzed the role of the Mu opioid receptor on B lymphocytes as a specific biomarker for FM and osteoarthritis (OA) patients. We enrolled three groups of females: FM patients, OA patients (chronic pain control group) and healthy subjects (pain-free negative control group). We collected blood samples to apply immunophenotyping analysis. Written tests were administrated for psychological analysis. Data were statistically analyzed. Final results showed that the percentage of Mu-positive B cells were statistically lower in FM and OA patients than in pain-free subjects. A low expression of Mu-positive B cell was not associated with the psychological characteristics investigated. In conclusion, here we propose the percentage of Mu-positive B cells as a biological marker for an objective diagnosis of chronic pain suffering patients, also contributing to the legitimacy of FM as a truly painful disease.

Highlights

Fibromyalgia (FM) is one of the most disabling chronic pain syndromes [1] affecting especially women and middle-aged people with a global prevalence between 0.2% and 6.6% [2,3,4]
Here we propose an observational, cross-sectional, single blind, diagnostic trial in order to investigate whether Mu opioid receptor on lymphocyte membranes could be considered as a FM biomarker or whether it could be a common marker for different chronic pain syndromes
Following inclusion and exclusion criteria assessment, clinical data were collected in a specific Case Report Form (CRF)including: demographics, clinical characteristics and pharmacological history (Table 1).Pain intensity analysis was measured using the 11-point numerical rating scale (NRS) test, where 0= No pain and 10= worst possible pain

Summary

Introduction

Fibromyalgia (FM) is one of the most disabling chronic pain syndromes [1] affecting especially women and middle-aged people with a global prevalence between 0.2% and 6.6% [2,3,4]. Neither specific diagnostic laboratory tests nor biomarkers are available to confirm FM diagnosis, especially in its specificity of chronic widespread pain (CWP), excluding some groundbreaking tests available in the near future [16] In this context, delays and misdiagnosis may frequently occur, with relevant consequences on patients’ life and treatment efficacy, as well as socioeconomic burdens on patients and the health care system [17,18,19,20,21]. Here we propose an observational, cross-sectional, single blind, diagnostic trial in order to investigate whether Mu opioid receptor on lymphocyte membranes could be considered as a FM biomarker or whether it could be a common marker for different chronic pain syndromes. In particular we focused on illness perception, coping and catastrophizing, pain acceptance and depression, as well as anxiety and stress-related symptoms [6,45,46,47,48,49]

Demographic and Clinical Characteristics

Mu Opioid Receptors on T and B Lymphocytes Membrane

Correlation between Duration of Pain and Mu Positive B Cells

Discussion

Trial Design

Participants

Clinical and Psychological Measurements

Blood Assays

Biological Analysis

Statistical Analysis