ISSN 1308-8734 | E-ISSN 1308-8742
Original Article
Neurotoxic Effects of Intrathecal Morphine and Tramadol in Rabbits
1 Atatürk Üniversitesi, Tıp Fakültesi, Anesteziyoloji ve Reanimasyon Anabilim Dalı, Erzurum  
2 Atatürk Üniversitesi Tıp Fakültesi Patoloji Anabilim Dalı  
Eurasian J Med 2006; 38: 61-67

Key Words: Complication, Intrathecal opioid analgesics, Morphine, Neurotoxicity, Rabbit, Tramadol

Objective: Intrathecal and epidural opioid analgesics have two important complications as respiratuary depression and tolerance. Tramadol have less the adverse effects. But, usage of intrathecally of tramadol has not supported by toxicological studies or There is very little study for this. For that reason, planning randomized two blind study, we aim to examine the differences which morphine and tramadol make in the spinal cord and blood-brain barrier with the help of light and fluorescence microscopy.


Materials and Methods: Thirty-six New Zealand rabbits were randomly assigned to three groups as group morphine (n=10), group Tramadol (n=16) and group saline (n=10). Morphine 200 μg, tramadol 200 μg and 0.9% saline solutions were administered to each group in 150 μl intrathecally using a modification of the tecniques of Malinovsky et al. Five of 2% Evans Blue was intravenously injected to all groups 5 h before intrathecal injection. Respiratory rate, cardiac rate, hemodynamic changes and arterial blood gas samples was noted four different times. Hot plate and Paw pinch tests performed after spinal injection. Behavioral disturbances, irritation signs, urination and defecation pattern changes and neurologic signs of rabbits were recorded during 5 to 7 days after spinal injection. The rabbits were lived 1 week, after sacrification with intracardiac paraformaldehid we searched brain and spinal cord histopathological and blood - brain barrier lesions of rabbits.

Results: Between intrathecal injection and death, none of the animals presented obvious neurologic impairment or behavioral disturbances. No sensory or motor blockade was also noted with 0.9% saline serum. Morphine and tramadol produced a complete block of the Paw Pinch and Hot Plate responses at dose used. Histopathologic and the blood-brain barrier study showed no evidence of neurotoxicity for morphine and tramadol in comparison with saline (p>0.05). Systolic arterial pressures, diastolic arterial pressures, and mean arterial pressures in morphine-injected rabbits were less than the preinjection values and less than saline treated controls during the fist 1h after intrathecal injection (p<0.05). But, with respect to heart rate, respiratory rate and arterial blood gases the differences are not significant (p>0.05). In the comparison of hemodynamic changes, respiratory rate, and arterial blood gases values between tramadol and saline groups, the differences are not significant (p>0.05).

Conclusion: We decided that intrathecally administered morphine and tramadol are not neurotoxic with respect to their histologic, physiologic, or behavioral actions. However, the administration of morphine and tramadol need further experimental studies.

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