title: Does pain mediate the pain interference with sleep problem in chronic pain? Findings from studies for management of diabetic peripheral neuropathic pain with duloxetine.
abstract: Although sleep problems are common in patients with chronic pain, it is unclear whether pain mediates (causes) impaired sleep. The relationship between pain and sleep has been difficult to investigate because of the potential confounds of depression and somnolence. This report used clinical trials data for duloxetine in the management of diabetic peripheral neuropathic pain (DPNP) to investigate the direction of this association. Data were pooled from three double-blind, randomized, placebo-controlled, 12-week trials of patients with DPNP without mood disorder (n=1,139). DPNP patients reporting somnolence and those who were receiving sedating concomitant medications were removed from the analyses (n=93). Efficacy measures included weekly mean scores for average daily pain severity, night pain severity, and pain interference with sleep. Duloxetine at 60 and 120 mg per day separated from placebo for average pain and night pain improvement as early as one week after treatment began, whereas sleep interference improvement separated from placebo at the three visits it was assessed (Weeks 4, 8, and 12). Change in sleep interference was moderately to strongly correlated (P<0.001) with changes in average pain (r=0.46) and nighttime pain severity (r=0.53). These results confirm the association between the improvement in daily pain and nighttime pain, and improvement in sleep interference for a large population without depression or somnolence. Although this association cannot establish causality, these results provide some evidence for the possibility that pain may mediate the sleep problem associated with DPNP and perhaps chronic pain in general.
authors.affiliation: Departments of Psychiatry, Neurological Surgery and Anesthesiology, Miller School of Medicine, University of Miami, Miami, Florida, USA. dfishbain@med.miami.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Fishbain
authors.forename: Jerry
authors.initials: J
authors.lastname: Hall
authors.forename: Adam L
authors.initials: AL
authors.lastname: Meyers
authors.forename: Jill
authors.initials: J
authors.lastname: Gonzales
authors.forename: Craig
authors.initials: C
authors.lastname: Mallinckrodt
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use; D002908:Chronic Disease; D015897:Comorbidity; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000453:epidemiology*; D004311:Double-Blind Method; D000068736:Duloxetine Hydrochloride; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy* / Q000453:epidemiology*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D007319:Sleep Initiation and Maintenance Disorders / Q000453:epidemiology* / Q000517:prevention & control*; D013876:Thiophenes / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D000928:Antidepressive Agents; D013876:Thiophenes; D000068736:Duloxetine Hydrochloride