Volume 20, Issue 6 (Iranian South Medical Journal 2018)
Iran South Med J 2018, 20(6): 527-539 |
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Ghasemloo K, Manaheji H, Dargahi L, pandamooz S. The Role of Spinal PKCγ in Tolerance and Hyperalgesia Induced by Repeated Morphine Administration in Male Rats. Iran South Med J 2018; 20 (6) :527-539
URL: http://ismj.bpums.ac.ir/article-1-904-en.html
URL: http://ismj.bpums.ac.ir/article-1-904-en.html
1- Department of Physiology, Shahid Beheshti University of Medical Sciences. Tehran, Iran
2- Department of Physiology, Shahid Beheshti University of Medical Sciences. Tehran, Iran
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences. Tehran, Iran ,manahejih@sbmu.ac.ir
3- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences. Tehran, Iran
2- Department of Physiology, Shahid Beheshti University of Medical Sciences. Tehran, Iran
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences. Tehran, Iran ,
3- Neuroscience Research Center, Shahid Beheshti University of Medical Sciences. Tehran, Iran
Abstract: (4052 Views)
Background: The aim of this study was to investigate the possible role of Protein Kinase Cᵧ (PKCᵧ) in morphine tolerance and induced hyperalgesia following repeated morphine administration in male rats.
Material and Methods: Rats were divided into 4 groups for testing. The groups consisted of control (saline), morphine tolerance and hyperalgesia, metformin, morphine tolerance and hyperalgesia + metformin. First morphine (10mg/kg, s.c) administrated daily up to 14 days subcutaneously. Hargreaves' behavioral test was performed to evaluate morphine tolerance. The test was ececuted before morphin injection and the results considered as “control” .Then the test repeated after the first dose of morphine on the first day and then on day14th after the last injection. To consider morphine hyperalgesia PWL (Paw Withdrawal Latency) was measured by Hargreaves test before and after first morphine injection on the first day and then on day 14th before the last injection of morphine and on day16th two days after the last injection of morphine. The expression of spinal PKCᵧ measured on day 14th and 16th. Metformin 100mg/kg, co-administrated with morphine daily up to 14 days then PWL and PKCᵧ expression were assessed as mentioned above.
Results: The results showed a significant tolerance and hyperalgesia on day 14th and 16th compareed to control. PKCᵧ expression also increased significantly on day 14th and 16th compareed to control. However, there was no significant difference in comparison between day 14th and day 16th. Co-administration of metformin and morphine up to 14 days increased PWL in morphine tolerance and reduced hyperalgesia and PKCᵧ expression.
Conclusion: The results showed that increasing of spinal PKCᵧ expression in chronic morphine administration might be involved in morphine tolerance mechanism and induced hyperalgesia.
Material and Methods: Rats were divided into 4 groups for testing. The groups consisted of control (saline), morphine tolerance and hyperalgesia, metformin, morphine tolerance and hyperalgesia + metformin. First morphine (10mg/kg, s.c) administrated daily up to 14 days subcutaneously. Hargreaves' behavioral test was performed to evaluate morphine tolerance. The test was ececuted before morphin injection and the results considered as “control” .Then the test repeated after the first dose of morphine on the first day and then on day14th after the last injection. To consider morphine hyperalgesia PWL (Paw Withdrawal Latency) was measured by Hargreaves test before and after first morphine injection on the first day and then on day 14th before the last injection of morphine and on day16th two days after the last injection of morphine. The expression of spinal PKCᵧ measured on day 14th and 16th. Metformin 100mg/kg, co-administrated with morphine daily up to 14 days then PWL and PKCᵧ expression were assessed as mentioned above.
Results: The results showed a significant tolerance and hyperalgesia on day 14th and 16th compareed to control. PKCᵧ expression also increased significantly on day 14th and 16th compareed to control. However, there was no significant difference in comparison between day 14th and day 16th. Co-administration of metformin and morphine up to 14 days increased PWL in morphine tolerance and reduced hyperalgesia and PKCᵧ expression.
Conclusion: The results showed that increasing of spinal PKCᵧ expression in chronic morphine administration might be involved in morphine tolerance mechanism and induced hyperalgesia.
Type of Study: Original |
Subject:
Pharmacology
Received: 2017/02/7 | Accepted: 2017/07/23 | Published: 2018/01/7
Received: 2017/02/7 | Accepted: 2017/07/23 | Published: 2018/01/7
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