title: Intracerebroventricular Application of Dexmedetomidine Produces Antinociception and Does not Cause Neurotoxicity in Rats.
abstract: BACKGROUND
  Alpha2 agonists contribute to pain control at the level of the medulla spinalis. Alpha2 agonists are generally added to local anaesthetics to prolong spinal or epidural anaesthesia time.
  
  
  OBJECTIVE
  In the present study, we aimed to evaluate the antinociceptive and neurotoxic effects of dexmedetomidine given intracerebroventricularly for 5 days.
  
  
  METHODS
  Animal experimentation.
  
  
  METHODS
  After intraventricular cannulation, rats (n=32) were divided into two groups (n=16 each). Rats in the dexmedetomidine group (Group D, n=16) received 3 µg (0.03 mL) dexmedetomidine and the control group (Group C, n=16) received 0.03 mL physiological serum through an intracerebroventricular catheter once a day, for 5 days. Antinociceptive, sedative, and motor effects were evaluated before the injection and for 90 min after injection. The tail-flick and hot plate tests were used to assess thermal nociceptive threshold. For histopathological evaluation, half of the rats in both groups were sacrificed on the 6(th) day and the remaining rats were sacrificed on the 21(st) day. Then the perfusion fixation method was applied. The first tissue section was obtained from the cervical spinal cord 1 cm distal to the proximal end of the spinal cord. The second sample was retrieved from the region 1 cm distal from the thoracic 13-lumbar 1 vertebra. On morphological evaluation, nonspecific changes like edema and gliosis, signs of neuronal degeneration demonstrating a severe reaction, and density of inflammatory cells were examined.
  
  
  RESULTS
  In dexmedetomidine-administered rats, on the first day reaction times at 5, 10, and 20 min and on the other days, reaction times at 5, 10, 20, and 30 min in hot plate tests were significantly longer compared with baseline values (p<0.05). In dexmedetomidine-administered rats, on the 1(st), 4(th), and 5(th) days reaction times at 5, 10, 20, 30, and 40 min and on the 2(nd) and 3(rd) days reaction times at 5, 10, 20, and 30 min in tail-flick tests were significantly longer compared with baseline values (p<0.05). First-degree sedation lasting for 60 min and first-degree motor block lasting for 30-40 min were observed in the dexmedetomidine group. Similar rates of nonspecific changes such as edema and gliosis were seen in both groups. Signs of severe reactions such as neuronal degeneration and diffuse inflammatory cell infiltration were not encountered in any group. There was no significant difference between groups according to morphological findings of the spinal cord on the 6(th) and 21(st) days (p>0.05).
  
  
  CONCLUSIONS
  We observed that intracerebroventricular administration of 3 μg dexmedetomidine produced antinociception and did not cause neurotoxicity.
authors.affiliation: Department of Anesthesiology and Reanimation, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Ersin
authors.initials: E
authors.lastname: Köksal
authors.affiliation: Department of Anesthesiology and Reanimation, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Karakaya
authors.affiliation: Department of Pathology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Bilge
authors.initials: B
authors.lastname: Can
authors.affiliation: Department of Physiology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Bozkurt
authors.affiliation: Department of Anesthesiology and Reanimation, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Sibel
authors.initials: S
authors.lastname: Barış
authors.affiliation: Department of Pharmacology, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Süleyman Sırrı
authors.initials: SS
authors.lastname: Bilge
authors.affiliation: Department of Anesthesiology and Reanimation, Ondokuz Mayıs University Faculty of Medicine, Samsun, Turkey.
authors.forename: Yasemin Burcu
authors.initials: YB
authors.lastname: Ustün
keywords: Dexmedetomidine; analgesia; neurotoxicity