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

Pharmacol Biochem Behav. 2011 Jul;99(1):94-9. doi: 10.1016/j.pbb.2011.04.009. Epub 2011 Apr 17.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Analgesics, Opioid / therapeutic use*
  • Animals
  • Levodopa / pharmacology
  • Levodopa / therapeutic use*
  • Male
  • Pain / drug therapy
  • Pain / enzymology
  • Pain / etiology
  • Pain Measurement / drug effects
  • Pain Measurement / methods
  • Pain Perception / drug effects
  • Pain Perception / physiology*
  • Periaqueductal Gray / drug effects
  • Periaqueductal Gray / enzymology*
  • Rats
  • Rats, Wistar
  • Sleep Deprivation / complications
  • Sleep Deprivation / drug therapy
  • Sleep Deprivation / enzymology*
  • Sleep, REM / drug effects
  • Sleep, REM / physiology*
  • Tyrosine 3-Monooxygenase / metabolism*

Substances

  • Analgesics, Opioid
  • Levodopa
  • Tyrosine 3-Monooxygenase