Pharmacological blockade of neurokinin1 receptor restricts morphine-induced tolerance and hyperalgesia in the rat
Author:
Rahban Mohammad1, Danyali Samira1, Zaringhalam Jalal2, Manaheji Homa2
Affiliation:
1. Department of Physiology, School of Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran 2. Neurophysiology Research Center, School of Medicine , Shahid Beheshti University of Medical Sciences , Tehran , Iran
Abstract
Abstract
Objectives
The most notable adverse side effects of chronic morphine administration include tolerance and hyperalgesia. This study investigated the involvement of dorsal root ganglion (DRG) protein kinase Cɛ (PKCɛ) expression during chronic morphine administration and also considered the relationship between DRG PKCɛ expression and the substance P- neurokinin1 receptor (SP- NK1R) activity.
Methods
Thirty-six animals were divided into six groups (n=6) in this study. In the morphine and sham groups, rats received 10 µg intrathecal (i.t.) morphine or saline for eight consecutive days, respectively. Behavioral tests were performed on days 1 and 8 before and after the first injections and then 48 h after the last injection (day 10). In the treatment groups, rats received NK1R antagonist (L-732,138, 25 µg) daily, either alone or 10 min before a morphine injection, Sham groups received DMSO alone or 10 min before a morphine injection. Animals were sacrificed on days 8 and 10, and DRG PKCɛ and SP expression were analyzed by western blot and immunohistochemistry techniques, respectively.
Results
Behavioral tests indicated that tolerance developed following eight days of chronic morphine injection. Hyperalgesia was induced 48 h after the last morphine injection. Expression of SP and PKCɛ in DRG significantly increased in rats that developed morphine tolerance on day 8 and hyperalgesia on day 10, respectively. NK1R antagonist (L-732,138) not only blocked the development of hyperalgesia and the increase of PKCɛ expression but also alleviated morphine tolerance.
Conclusions
Our results provide evidence that DRG PKCɛ and SP-NK1R most likely participated in the generation of morphine tolerance and hyperalgesia. Pharmacological inhibition of SP-NK1R activity in the spinal cord suggests a role for NK1R and in restricting some side effects of chronic morphine. All experiments were performed by the National Institute of Health (NIH) Guidelines for the Care and Use of Laboratory Animals (NIH Publication No. 80-23, revised1996) and were approved by the Animal Ethics Committee of Shahid Beheshti University of Medical Sciences, Tehran, Iran (IR.SBMU.MSP.REC.1396.130).
Publisher
Walter de Gruyter GmbH
Subject
Anesthesiology and Pain Medicine,Neurology (clinical)
Reference59 articles.
1. Hamilton, GR, Baskett, TF. In the arms of morpheus the development of morphine for postoperative pain relief. Can J Anesth 2000;47:36–371. https://doi.org/10.1007/BF03020955. 2. Roeckel, LA, Le Coz, GM, Gaveriaux-Ruff, C, Simonin, F. Opioid-induced hyperalgesia: cellular and molecular mechanisms. Neuroscience 2016;338:160–82. https://doi.org/10.1016/j.neuroscience.2016.06.029. 3. Liu, D, Zhou, Y, Peng, Y, Su, P, Li, Z, Xu, Q, et al.. Endoplasmic reticulum stress in spinal cord contributes to the development of morphine tolerance. Front Mol Neurosci 2018;11:72. https://doi.org/10.3389/fnmol.2018.00072. 4. Mao, J, Price, DD, Mayer, DJ. Mechanisms of hyperalgesian and morphine tolerance: a current view of their possible interactions. Pain 1995;62:259–74. https://doi.org/10.1016/0304-3959(95)00073-2. 5. Oladosu, FA, Conrad, MS, O’Buckley, SC, Rashid, NU, Slade, GD, Nackley, AG. Mu opioid splice variant MOR-1K contributes to the development of opioid-induced hyperalgesia. PloS One 2015;10:e0135711. https://doi.org/10.1371/journal.pone.0135711.
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