Associations Among Nitric Oxide and Enkephalinases With Fibromyalgia Symptoms

Nurs Res. 2021 Mar-Apr;70(2):E11-E20. doi: 10.1097/NNR.0000000000000496.


Background: Fibromyalgia (FM) is a complex syndrome of uncertain etiology, characterized by the presence of widespread pain. Both nitric oxide and enkephalinases modulate pain perception.

Objectives: The aim of this study was to evaluate the relationships among serum nitric oxide levels, oxytocinase activity, and enkephalin-degrading aminopeptidase (EDA) activity with pain-related clinical manifestations in women with FM.

Methods: We performed an observational case study in a population of 58 women diagnosed with FM. Serum nitric oxide levels were analyzed by an ozone chemiluminescence-based assay. Both serum oxytocinase and EDA activities were fluorometrically determined. Pain threshold and pain magnitude were evaluated using the PainMatcher. The pressure pain thresholds were measured using a digital pressure algometer. We used a visual analog scale, the Central Sensitization Inventory, the Revised Fibromyalgia Impact Questionnaire, and the Beck Anxiety Inventory to assess the global level of pain, the symptoms associated with the central sensitization syndrome, the severity of FM, and the anxiety level, respectively.

Results: Multiple linear regression analysis adjusted by age, body mass index, and menopause status revealed significant associations between nitric oxide levels and dominant occiput pressure pain thresholds, nondominant occiput pressure pain thresholds, and FM effects. Significant associations of oxytocinase activity with the visual analog scale and dominant knee pressure pain thresholds were also found. Moreover, results showed a significant association between high EDA activity levels and dominant second-rib pressure pain thresholds.

Discussion: Our data have shown significant relationships of serum nitric oxide levels and oxytocinase and EDA activities with some body pressure pain thresholds, the daily activity level, and the global intensity of pain in women with FM. These results suggest that pain, which is the main symptom of this syndrome, may be related to alterations in nitric oxide levels and in oxytocinase and EDA activities in patients with FM.

MeSH terms

  • Adult
  • Aminopeptidases / blood*
  • Female
  • Fibromyalgia / blood*
  • Fibromyalgia / complications
  • Fibromyalgia / physiopathology
  • Humans
  • Middle Aged
  • Nitric Oxide / blood*
  • Pain / blood
  • Pain / diagnosis*
  • Pain / etiology
  • Pain Measurement
  • Pain Threshold
  • Severity of Illness Index


  • Nitric Oxide
  • Aminopeptidases
  • enkephalin degrading enzyme