title: Pain hypersensitivity induced by paradoxical sleep deprivation is not due to altered binding to brain mu-opioid receptors.
abstract: Previous studies have established a relationship between sleep disruption and pain, and it has been suggested that hyperalgesia induced by paradoxical sleep deprivation (PSD) could be due to a reduction of opioidergic neurotransmission in the brain. In the present study rats deprived of sleep for 96 h as well as rats allowed to recover for 24h after PSD and normal controls received vehicle or morphine (2.5, 5 and 10 mg/kg, i.p.) and were tested on a hot plate 1h later. Quantitative receptor autoradiography was used to map alterations in binding to brain mu-opioid receptors in separate groups. Results demonstrated that PSD induced a significant reduction in thermal pain threshold, as measured by paw withdrawal latencies. This effect did not return to baseline control values after 24h of sleep recovery. The usual analgesic effect of morphine was observed in the control group but not in PSD or rebound groups except at the highest dose (10 mg/kg). Binding of [3H]DAMGO to mu sites did not differ significantly among the three groups in any of the 33 brain regions examined. These results do not exclude the participation of the opioid system in PSD-induced pain hypersensitivity since sleep-deprived rats were clearly resistant to morphine. However, the fact no changes were seen in [3H]DAMGO binding indicates that mechanisms other than altered mu-opioid binding must be sought to explain the phenomenon.
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo, Escola Paulista de Medicina (UNIFESP/EPM), R. Napoleão de Barros, 925, V. Clementino 04024-002, São Paulo, SP, Brazil.
authors.forename: Danielle C
authors.initials: DC
authors.lastname: Nascimento
authors.forename: Monica L
authors.initials: ML
authors.lastname: Andersen
authors.forename: Débora Cristina
authors.initials: DC
authors.lastname: Hipólide
authors.forename: José N
authors.initials: JN
authors.lastname: Nobrega
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
mesh_terms: D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism*; D012892:Sleep Deprivation / Q000150:complications*; D018709:Statistics, Nonparametric
chemical_list: D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009020:Morphine