Diagnosis, Functionality and Animal Models in Fibromyalgia Research

Credible fibromyalgia (FM) research, at least in the eyes of mainstay scientific researchers, has been held back for decades for three significant reasons: (1) diagnostic criteria, (2) functionality evaluations, and (3) lack of animal models. Since an FM clinical diagnosis has been elusive and because the research community needed some way to measure symptom severity, benefit of treatment, types of symptoms, etc., the American College of Rheumatology 1990 Fibromyalgia Diagnostic Criteria was developed.  A large group of scientists from several different universities developed and published the criteria in the Journal of Rheumatology. However, these were considered research criteria and were never intended to be used as strict diagnostic criteria in clinical (physician) practices. But, through the years the ACR FM diagnostic criteria did make its way into treating doctors’ offices, mostly through continuing medical education programs.
 
Since 2010 at least two more accepted FM diagnostic tools were introduced to the medical community.  These new diagnostic criteria rely on other dynamics rather than the need for a physical examination identifying 11 of 18 tender points and a history of chronic widespread pain lasting longer than three months in all four quadrants of the body. The 2011 FM survey criteria were intended for use in epidemiological studies and represent an alternative method to assess FM.  The 2011 criteria include a self report survey that is administered on a single piece of paper and have the advantage of conceptualizing the core symptoms of FM as a continuum of pain centralization or “fibromyalgia-ness.” It is the consensus of the research community that these criteria are appropriate for clinical use in physician offices.
 
Along with diagnostic criteria, it became apparent that a measurement of function was paramount to understanding the impact of FM on a person’s daily life.  Baseline functions and study outcome of improved function also needed a measurement tool usable in FM scientific research studies. In the late 1980s Carol Burckhardt, PhD, Sharon Clark, NP, PhD, and Robert Bennett, MD (all part of the Oregon Health and Science University Fibromyalgia Research Group), developed the Fibromyalgia Impact Questionnaire (FIQ).  In 1991 the FIQ was published in the Journal of Rheumatology.  It consisted of the following questions (all 1980s-oriented and strongly geared toward women), the answers of which were then statistically analyzed:
 
1.   Were you able to        
  Always Most times Occasionally Never

      a.  do laundry with a washer and dryer?

0 1 2 3
      b.  prepare meals? 0 1 2 3
      c.  vacuum a rug? 0 1 2 3
      d.  make beds? 0 1 2 3
      e.  walk several blocks 0 1 2 3
      f.  visit friend/relatives 0 1 2 3
      g.  do yard work 0 1 2 3
      h.  drive a car 0 1 2 3
 
 
2.  Of the last 7 days, how many days did you feel good?
        1       2       3       4       5       6       7
 
3.  How many days in the past week did you miss work because of your fibromyalgia?  (If you don't have a job outside the home, leave this item blank.)
        1       2       3       4       5
 
4.  When you did go to work, how much did pain or other symptoms of your fibromyalgia interfere with your ability to do your job?
       ___________________________________________________________________        No problem                                                                               Great difficulty
 
5.  How bad has your pain been?
      ___________________________________________________________________       No pain                                                                                  Very severe pain
 
 
6.  How tired have you been?
      ___________________________________________________________________       No tiredness                                                                                    Very tired
 
7.  How have you felt when you got up in the morning?
      ___________________________________________________________________       Awoke well rested                                                                  Awoke very tired
 
8.  How bad has your stiffness been?
      ___________________________________________________________________       No stiffness                                                                                       Very stiff
 
9.  How tense, nervous or anxious have you felt?
      ___________________________________________________________________       No Tense                                                                                        Very tense
 
10.  How depressed or blue have you felt?
       __________________________________________________________________       Not depressed                                                                         Very depressed
 
The original FIQ has been used in some 300 research publications, and has been translated into 46 languages.
 
In 2009 an updated version of the FIQ was authored by Drs. Robert Bennett and Ron Friend, along with their colleagues at the Oregon Health and Science University. The resulting FIQR updated the original FIQ to remedy issues that became apparent over the years.  The FIQR replaced the original FIQ for routine use in fibromyalgia related studies and routine clinical use. The main revision corrected reported problems encountered in the original FIQ and eliminated the complex scoring of the original FIQ. It has been endorsed by the leading authorities in fibromyalgia research.
 
To see the FIQR questions and review its updated information please click here http://fiqrinfo.ipage.com/.
 
The last problem hindering better recognition and acceptance of FM research is the lack of chronic pain animal models to study. In his April 16, 2014, published article in JAMA, Dr. Dan Clauw, pointed out that many animal models of hyperalgesia/allodynia exist, but they lack the other features of the human FM phenotype. Secondly, animal studies are usually performed on inbred strains of animals that do not exhibit the genetic heterogeneity humans have.  According to Dr. Clauw, “Classic animal models also measure ‘pain behaviors’ mediated by spinal reflexes and generally do not probe the central nervous system response to peripheral stimuli.”  Based on this information, development of phenotypically relevant animal models using operant paradigms as outcomes will likely be very useful for bidirectional translation and better FM science.
 
FM scientific research has clearly advanced over the past 25+ years without a clinical diagnosis and development of useful animal models.  However, getting experienced bench scientists to acknowledge important FM scientific breakthroughs is still a struggle. Advances in FM diagnosis investigated by Dr. Bruce Gillis and resulting in the first-ever FM clinical blood test (FM/a blood test) not only helps raise medical and public credibility of this disorder, but also offers a better path of research for competent scientists to follow.  After studying the findings of the FM/a blood test, perhaps a phenotypically relevant  animal model will be developed that will help uncover more FM scientific mysteries.