title: Sleep deprivation aggravates median nerve injury-induced neuropathic pain and enhances microglial activation by suppressing melatonin secretion.
abstract: OBJECTIVE
  Sleep deprivation is common in patients with neuropathic pain, but the effect of sleep deprivation on pathological pain remains uncertain. This study investigated whether sleep deprivation aggravates neuropathic symptoms and enhances microglial activation in the cuneate nucleus (CN) in a median nerve chronic constriction injury (CCI) model. Also, we assessed if melatonin supplements during the sleep deprived period attenuates these effects.
  
  
  METHODS
  Rats were subjected to sleep deprivation for 3 days by the disc-on-water method either before or after CCI. In the melatonin treatment group, CCI rats received melatonin supplements at doses of 37.5, 75, 150, or 300 mg/kg during sleep deprivation. Melatonin was administered at 23:00 once a day.
  
  
  METHODS
  Male Sprague-Dawley rats, weighing 180-250 g (n = 190), were used.
  
  
  METHODS
  Seven days after CCI, behavioral testing was conducted, and immunohistochemistry, immunoblotting, and enzyme-linked immunosorbent assay were used for qualitative and quantitative analyses of microglial activation and measurements of proinflammatory cytokines.
  
  
  RESULTS
  In rats who underwent post-CCI sleep deprivation, microglia were more profoundly activated and neuropathic pain was worse than those receiving pre-CCI sleep deprivation. During the sleep deprived period, serum melatonin levels were low over the 24-h period. Administration of melatonin to CCI rats with sleep deprivation significantly attenuated activation of microglia and development of neuropathic pain, and markedly decreased concentrations of proinflammatory cytokines.
  
  
  CONCLUSIONS
  Sleep deprivation makes rats more vulnerable to nerve injury-induced neuropathic pain, probably because of associated lower melatonin levels. Melatonin supplements to restore a circadian variation in melatonin concentrations during the sleep deprived period could alleviate nerve injury-induced behavioral hypersensitivity.
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Huang
authors.forename: Rayleigh Ping-Ying
authors.initials: RP
authors.lastname: Chiang
authors.forename: Chih-Li
authors.initials: CL
authors.lastname: Chen
authors.forename: Yi-Ju
authors.initials: YJ
authors.lastname: Tsai
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008475:Median Nerve / Q000293:injuries*; D008526:Medulla Oblongata / Q000166:cytology; D008550:Melatonin / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D009437:Neuralgia / Q000150:complications* / Q000209:etiology* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012892:Sleep Deprivation / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D008550:Melatonin
keywords: median nerve; melatonin; microglia; neuropathic pain; sleep deprivation