Chronic Pain and Cannabinoids
According to the American College of Rheumatology (ACR) definition, fibromyalgia is a syndrome of widespread muscle pain (over 3 months) and stiffness with 11 or more characteristic tender points on palpation (see Figure 1).1 It affects 2% of the population, predominantly females, with the most common age at presentation of 40 to 50 years.2 Symptoms in the fibromyalgia syndrome (FMS) include:
- 1) musculoskeletal complaints: “hurt all over,” stiffness, swollen feeling in tissues;
2) nonmusculoskeletal: fatigue, poor sleep (with reduced stages 3/4 slow wave sleep),3-5 and paresthesia; and
3) associated syndromes such as irritable bowel syndrome (IBS; 41.8% of FMS patients),6 dysmenorrhea,,7 female urethral syndrome,,8 endometriosis,,9 noncardiac chest pain,,10 plantar heel pain,,11 migraine headache (45%),,12 temporomandibular joint pain,,13 sinusitis,,14 and Sjogren’s syndrome.,15 A higher incidence of carpal tunnel syndrome,16 and raynaud’s syndrome,17 may explain some of the paresthesia complaints.
Characteristic Tender Points of Fibromyalgia
Eleven out of 18 tender points is required to make a diagnosis of fibromyalgia according to criteria stablished by the American College of Rheumatology.,1
- suboccipital muscle insertions
anterior aspect of C5-7 intertransverse
- midpoint of upper trapezius muscles
- supraspinatus origin above spine of
- second rib lateral to costochondral
- extensor muscle: 2 cm distal to lat.
- gluteal: upper outer quadrant of
- posterior to greater trochanter prominence
- medial fat pad of knee: proximal to joint line
Higher anxiety (63.8%) and depression have also been reported.,18,19 The economic impact of this syndrome is significant. Chronic musculoskeletal pain is the number one cause of disability (under age 45) in North America, the number two cause for visits to the primary care physician and for workplace absences and the number three cause for hospitalizations with over 250,000 spinal fusions carried out in the USA. It is estimated that the direct medical cost of FMS to the U.S. economy is in excess of $16 billion annually.,20 Despite such costs, effective long-term treatment remains elusive.
Etiology of Fibromyalgia
Postulated risk factors for the development of FMS include a family history of this condition,,21 a family history of depression and/or alcoholism in first degree relatives,,22 childhood physical and sexual abuse, eating disorders, drug abuse,,23,24 hypermobile joint syndrome.,25 FMS has also been documented after physical trauma,26,27 and whiplash,,28 but the causal relationship has not been established in a consensus report on FMS and disability.,29 A review on psychosocial aspects concluded that the view that FMS is caused by stress or abuse is unproven and that there is no evidence that communicating such a diagnosis causes iatrogenic consequences.,30
It has also been postulated that viral infections may play an etiologic role.,31 70% of FMS patients meet the Centers for Disease Control and Prevention criteria for chronic fatigue syndrome (CFS),32 and 70% of CFS patients meet the ACR criteria for FMS.,33 The usual routine laboratory tests such as basic hematology, ESR, muscle enzymes, rheumatoid factor and ANA are all normal.,34 CFS researchers suggest that deregulation of the 2.5A synthetase Rnase L antiviral pathway may be the pathophysiological reason.,35 Muscle biopsy,36 and MRI spectroscopy,37 studies which are controlled have proven to be non-diagnostic. More recent electron microscopy suggests ultra-structural changes including increased DNA fragmentation (possibly due to persistent focal muscle contractions),38. Reduced growth hormone secretion;,39 and elevated CSF substance P,,40 homocysteine,,41 nerve growth factor levels,42 as well as abnormal neuroendocrine challenge tests,43-45 and abnormal functional MRI studies,46-50 suggest a central pain mechanism but no reliable diagnostic test has yet to be established. The most recent research suggests a clinical endocannabinoid deficiency as an etiological cause.,51