title: Increased pain perception and attenuated opioid antinociception in paradoxical sleep-deprived rats are associated with reduced tyrosine hydroxylase staining in the periaqueductal gray matter and are reversed by L-dopa.
abstract: Paradoxical sleep deprivation (PSD) increases pain sensitivity and reduces morphine antinociception. Because dopaminergic neurons in the periaqueductal gray matter (PAG) participate in pain modulation and opioid-induced antinociception, we evaluated the effects of PSD on thermal pain sensitivity, morphine- and L-DOPA-induced antinociception and dopaminergic functionality in the PAG by assessing tyrosine hydroxylase (TH) immunoreactivity. Rats that were subjected to 96h of PSD received vehicle, morphine (2.5, 5 or 10mg/kg), L-DOPA (50 or 100mg/kg) or L-DOPA (50mg/kg)+morphine (2.5 and 5mg/kg) and were tested with a 46°C hot plate 1h after. The paw withdrawal latency responses to the hot plate were decreased in PSD rats and were modified by the highest dose of morphine, L-DOPA and L-DOPA+morphine. Analgesic effects were observed in control groups for all of the morphine doses as well as 100mg/kg of L-DOPA and L-DOPA (50mg/kg)+morphine (5mg/kg). The number of cell bodies that were immunopositive for TH in the PAG was reduced in PSD rats. In conclusion, increased thermal sensitivity was reversed by L-DOPA and could be caused by a reduction TH levels in the PAG. Our data also suggest a relationship between central dopaminergic networks and opiate-induced analgesia in rats.
authors.affiliation: Department of Pharmacology and Psychobiology, Institute of Biology, State University of Rio de Janeiro, Av. 28 de Setembro, 87-Fundos, 20551-030, Rio de Janeiro, Brazil.
authors.forename: Gabriela O
authors.initials: GO
authors.lastname: Skinner
authors.forename: Fabio
authors.initials: F
authors.lastname: Damasceno
authors.forename: Aline
authors.initials: A
authors.lastname: Gomes
authors.forename: Olga M M S
authors.initials: OM
authors.lastname: de Almeida
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010146:Pain / Q000188:drug therapy / Q000201:enzymology / Q000209:etiology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D058748:Pain Perception / Q000187:drug effects / Q000502:physiology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012892:Sleep Deprivation / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*
chemical_list: D000701:Analgesics, Opioid; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase