title: Effect of spinal morphine after long-term potentiation of wide dynamic range neurones in the rat.
abstract: BACKGROUND
  Studies have shown that long-term increase in the excitability of single wide dynamic range neurones in the spinal dorsal horn of rats may be induced after tetanic stimulation to the sciatic nerve. This sensory event is possibly an in vivo counterpart of long-term potentiation, described in the brain. This study investigated whether this phenomenon occurs in the halothane-anesthetized rat and whether the antinociceptive effects of spinally administered morphine are altered when tested on the enhanced activity.
  
  
  METHODS
  Single unit extracellular recordings were made in three different groups of halothane-anesthetized rats (n = 6 in each group). In group 1, the evoked neuronal responses of wide dynamic range neurones by a single electrical stimulus to the peripheral nerve were recorded every 4 min, for 1 h before (baseline) and for 3 h after brief high-frequency conditioning stimulation of the sciatic nerve. In group 2, morphine was applied onto the spinal cord after long-term potentiation had been established. Increasing concentrations of morphine were added until the C fiber-evoked responses were abolished; this was followed by naloxone reversal. In group 3, the same protocol as in group 2 was used except a waiting period substituted for the electrical conditioning.
  
  
  RESULTS
  The C fiber-evoked responses were significantly increased (P < 0.001) after conditioning compared with baseline and those in control animals. Further, significantly higher concentrations of morphine (P = 0.008) were needed to abolish the C fiber-evoked responses in tetanized animals than in control animals. Naloxone reversed the effects of morphine to the predrug potentiated baseline in group 2, showing that opioids do not block the maintenance of spinal long-term potentiation.
  
  
  CONCLUSIONS
  Long-term potentiation of C fiber-evoked responses also can be induced in halothane-anesthetized rats, and morphine seems to have less potency during such conditions. These data suggest that long-term potentiation-like mechanisms may underlie some forms of hyperalgesia associated with a reduced effect of morphine.
authors.affiliation: Neuropharmacology of Pain Group, Department of Pharmacology, University College London, United Kingdom. lars.jorgen.rygh@pki.uib.no
authors.forename: L J
authors.initials: LJ
authors.lastname: Rygh
authors.forename: M
authors.initials: M
authors.lastname: Green
authors.forename: N
authors.initials: N
authors.lastname: Athauda
authors.forename: A
authors.initials: A
authors.lastname: Tjølsen
authors.forename: A H
authors.initials: AH
authors.lastname: Dickenson
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000704:Analysis of Variance; D000769:Anesthesia, Inhalation; D000818:Animals; D004357:Drug Synergism; D004558:Electric Stimulation; D004594:Electrophysiology; D006221:Halothane; D007278:Injections, Spinal; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D020671:Posterior Horn Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine; D006221:Halothane