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 96 h of PSD received vehicle, morphine (2.5, 5 or 10 mg/kg), L-DOPA (50 or 100 mg/kg) or L-DOPA (50 mg/kg) + morphine (2.5 and 5 mg/kg) and were tested with a 46 °C hot plate 1 h 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 100 mg/kg of L-DOPA and L-DOPA (50 mg/kg) + morphine (5 mg/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.