Ultra-micronized Palmitoylethanolamide Effects on Sleep-wake Rhythm and Neuropathic Pain Phenotypes in Patients with Carpal Tunnel Syndrome: An Open-label, Randomized Controlled Study

CNS Neurol Disord Drug Targets. 2018;17(4):291-298. doi: 10.2174/1871527317666180420143830.


Background: Patients with carpal tunnel syndrome often suffer from fragmentary sleep. This study was designed to assess the effectiveness of treatment with ultramicronized palmitoylethanolamide in reducing pain intensity and improving quality of sleep in patients with neuropathic pain due to carpal tunnel syndrome.

Methods: An open, controlled study was conducted on 42 patients awaiting carpal tunnel syndrome surgery, suffering from sleep disorders and painful symptoms and randomized into two groups. One group received ultramicronized palmitoylethanolamide (600 mg twice daily) during the pre- and postsurgery periods, while the other group did not receive any treatment except surgical therapy. The primary outcome measure was sleep quality assessment by the Pittsburgh Sleep Quality Index, with secondary outcome as painful symptomatology intensity evaluated by the Numeric Rating Scale.

Results: At the end of the pre-surgery period (T1) there was a highly significant improvement (p<0.0001) in overall sleep quality with an increase of continuous sleep time and a reduction of sleep latency and disturbances as well as a significant mitigation (p<0.0001) of painful symptoms in favor of the treated group.

Conclusion: Disturbed sleep patterns are very common in patients suffering from neuropathic pain due to carpal tunnel syndrome. Our results, albeit preliminary, suggest that ultramicronized palmitoylethanolamide administration favors a clear improvement of sleep quality, confirming a correlation between sleep disorders and pain intensity.

Keywords: Carpal tunnel syndrome; Hyperalgesia; Painfulness; Sleep duration; Sleep latency; Sleep quality; Ultra-micronized palmitoylethanolamide..

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carpal Tunnel Syndrome / complications
  • Carpal Tunnel Syndrome / physiopathology
  • Carpal Tunnel Syndrome / therapy*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neuralgia / etiology
  • Neuralgia / physiopathology
  • Neuralgia / therapy*
  • Pain Measurement
  • Phenotype
  • Sleep / physiology*
  • Sleep Wake Disorders / physiopathology
  • Sleep Wake Disorders / therapy*
  • Treatment Outcome