Volume 24, Issue 6 (10-2020)                   ibj 2020, 24(6): 374-380 | Back to browse issues page

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Mehrabadi S, Karimiyan S M, Ashabi G, Moradbeygi K, Hoseini M. Repeated Administration of Baclofen Modulates TRPV-1 Channel Expression by PKC Pathway in Dorsal Root Ganglia of Spinal Cord in Morphine Tolerance Model of Rats. ibj. 2020; 24 (6) :374-380
URL: http://ibj.pasteur.ac.ir/article-1-3172-en.html
Background: Tolerance and dependence to anti-nociceptive effect of morphine restricted its use. Nowadays co-administration of morphine and other drugs suggests diminishing this tolerance. Baclofen is one of the drugs that may be beneficial in the attenuation of tolerance to morphine. Studies have shown that changes in transient receptor potential vanilloid type 1 (TRPV-1) expression during administration of morphine have a pivotal role in developing morphine tolerance. Therefore, the effect of baclofen on TRPV-1 expression during chronic administration of morphine was investigated in this study. Methods: A total of 48 rats were divided into four groups of control, morphine single injection, morphine tolerance, and morphine tolerance + baclofen. To induce morphine tolerance in rats, animals received 10 mg/kg of i.p. morphine sulfate once a day for 10 days. In the treatment group, baclofen (0.5 mg/kg) was injected for 10 days, before morphine injection. Finally, to evaluate baclofen treatment on morphine analgesia and hyperalgesia, thermal hyperalgesia and formalin test were used. TRPV-1 and protein kinase C (PKC) expression and protein production in DRG of spinal cord were then evaluated by real-time PCR and Western blot. Results: In baclofen treatment group, thermal hyperalgesia and formalin test improved in comparison with morphine tolerance group. In morphine tolerance group, both TRPV-1/PKC gene expression and protein levels  increased in comparison with the control group. However, following the baclofen treatment, the TRPV-1 and PKC levels  decreased. Conclusion: Baclofen can enhance anti-nociceptive effect of morphine by modulating TRPV-1 channel and PKC activity.
Type of Study: Full Length | Subject: Related Fields

1. Bao Y, Gao Y, Yang L, Kong X, Yu J, Hou W, Hua B. The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence. Channels 2015; 9(5): 235-243. [DOI:10.1080/19336950.2015.1069450]
2. Corder G, Tawfik VL, Wang D, Sypek EI, Low SA, Dickinson JR, Sotouded C, Clark D, Barres B, Bohlen CJ, Scherer G. Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia. Nature medicine 2017; 23(2):164-173. [DOI:10.1038/nm.4262]
3. Mehrabadi S, Karimiyan SM. Morphine tolerance effects on neurotransmitters and related receptors: Definition, Overview and update. Journal of pharmaceutical research international. 2018; 23: 1-11. [DOI:10.9734/JPRI/2018/41936]
4. Pan Y, Sun X, Jiang L, Hu L, Han Y, Qian C, Song C, Qian Y, Liu W. Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation. Journal of neuroinflammation 2016; 13(1): 294. [DOI:10.1186/s12974-016-0754-9]
5. Lilius T, Kangas E, Niemi M, Rauhala P, Kalso E. Ketamine and norketamine attenuate oxycodone tolerance markedly less than that of morphine: from behaviour to drug availability. British journal of anaesthesia 2018; 120(4): 818-826. [DOI:10.1016/j.bja.2017.11.081]
6. Manaheji H, Mehrabadi S. Effect of Sub-effective dose of GABA agonists on attenuation of morphine tolerance in rats: Behavioral and electrophysiological studies. International journal of advanced biological and biomedical research 2019; 7(4): 326-334. [DOI:10.33945/SAMI/IJABBR.2019.4.4]
7. Meir R, Totsch S, Landis A, Quinn T, Sorge R. (201) Baclofen and opioid synergism in mice: new insights and potential treatments. The journal of pain 2017; 18(4): S26. [DOI:10.1016/j.jpain.2017.02.108]
8. Mehrabadi S, Shahabeddin Sadr S. GABA agonists could decrease hyperalgesia and NO serum level in morphine tolerance model. International journal of advanced biological and biomedical research 2018; 6(2): 129-134.
9. Haney M, Hart CL, Foltin RW. Effects of baclofen
10. on cocaine self-administration. Neuropsycho-pharmacology 2006; 31(8): 1814-1821. [DOI:10.1038/sj.npp.1300999]
11. Knapp DJ, Overstreet DH, Breese GR. Baclofen blocks expression and sensitization of anxiety-like behavior in an animal model of repeated stress and ethanol withdrawal. Alcoholism: clinical and experimental research 2007; 31(4): 582-595. [DOI:10.1111/j.1530-0277.2007.00342.x]
12. Eidson LN, Inoue K, Young LJ, Tansey MG, Murphy AZ. Toll-like receptor 4 mediates morphine-induced neuroinflammation and tolerance via soluble tumor necrosis factor signaling. Neuropsychopharmacology 2017; 42(3): 661-670. [DOI:10.1038/npp.2016.131]
13. Hanack C, Moroni M, Lima WC, Wende H, Kirchner M, Adelfinger L, GABA blocks pathological but not acute TRPV1 pain signals. Cell 2015; 160(4): 759-770. [DOI:10.1016/j.cell.2015.01.022]
14. Laing RJ, Dhaka A. ThermoTRPs and pain. The neuroscientist 2016; 22(2): 171-187. [DOI:10.1177/1073858414567884]
15. Uta D, Yoshimura M, Koga K. Chronic pain models amplify transient receptor potential vanilloid 1 (TRPV1) receptor responses in adult rat spinal dorsal horn. Neuropharmacology 2019; 160: 107753. [DOI:10.1016/j.neuropharm.2019.107753]
16. Shibukawa Y, Sato M, Kimura M, Sobhan U, Shimada M, Nishiyama A, Kawaguchi A, Soya M, Kuroda H, Katakure K, Ichinohe T, Tazaki TM, Odontoblasts as sensory receptors. Pflügers archiv European journal of Physiology 2015; 467(4): 843-863. [DOI:10.1007/s00424-014-1551-x]
17. Hagenacker T, Ledwig D, Büsselberg D. Feedback mechanisms in the regulation of intracellular calcium ([Ca2+]i) in the peripheral nociceptive system: role of TRPV-1 and pain related receptors. Cell calcium 2008; 43(3): 215-227. [DOI:10.1016/j.ceca.2007.05.019]
18. Hagenacker T, Czeschik J, Schäfers M, Büsselberg D. Sensitization of voltage activated calcium channel currents for capsaicin in nociceptive neurons by tumor-necrosis-factor-α. Brain research bulletin 2010; 81(1): 157-163. [DOI:10.1016/j.brainresbull.2009.09.012]
19. Cheng JK, Ji RR. Intracellular signaling in primary sensory neurons and persistent pain. Neurochemical research 2008; 33(10): 970-1978. [DOI:10.1007/s11064-008-9711-z]
20. Zhou Y, Zhou ZS, Zhao ZQ. PKC regulates capsaicin-induced currents of dorsal root ganglion neurons in rats. Neuropharmacology 2001; 41(5): 601-608. [DOI:10.1016/S0028-3908(01)00106-X]
21. Chen WH, Chang YT, Chen YC, Cheng SJ, Chen CC. Spinal protein kinase C/extracellular signal-regulated kinase signal pathway mediates hyperalgesia priming. Pain 2018; 159(5): 907-918. [DOI:10.1097/j.pain.0000000000001162]
22. Nazıroğlu M. Activation of TRPM2 and TRPV1 channels in dorsal root ganglion by NADPH oxidase and protein kinase C molecular pathways. Journal of molecular neuroscience 2017; 61(3): 425-435. [DOI:10.1007/s12031-017-0882-4]
23. Wang S, Joseph J, Ro JY, Chung MK. Modality-specific mechanisms of PKC-induced hypersensitivity of TRPV1. Pain 2015; 156(5): 931-941. [DOI:10.1097/j.pain.0000000000000134]
24. Zhang H, Cang CL, Kawasaki Y, Liang LL, Zhang YQ, Ji RR. Neurokinin-1 receptor enhances TRPV1 activity in primary sensory neurons via PKCε. The journal of neuroscience 2007; 27(44):12067-12077. [DOI:10.1523/JNEUROSCI.0496-07.2007]
25. Sikand P, Premkumar LS. Potentiation of glutamatergic synaptic transmission by protein kinase C-mediated sensitization of TRPV1 at the first sensory synapse. The journal of physiology 2007; 581(2): 631-647. [DOI:10.1113/jphysiol.2006.118620]
26. Bhave G, Hu HJ, Glauner KS, Zhu W, Wang H, Brasier DJ, Oxford GS, Gereau RW 4th. Protein kinase C phosphorylation sensitizes but does not activate the capsaicin receptor transient receptor potential vanilloid 1 (TRPV1). Proceedings of the national academy of sciences 2003; 100(21): 12480-12485. [DOI:10.1073/pnas.2032100100]
27. Roca-Vinardell A, Berrocoso E, Llorca-Torralba M, García-Partida J, Gibert-Rahola J, Mico J. Involvement of 5-HT1A/1B receptors in the antinociceptive effect of paracetamol in the rat formalin test. Neurobiology of pain 2018; 3: 15-21. [DOI:10.1016/j.ynpai.2018.01.004]
28. Jokinen V, Lilius T, Laitila J, Niemi M, Rauhala P, Kalso E. Pregabalin enhances the antinociceptive effect of oxycodone and morphine in thermal models of nociception in the rat without any pharmacokinetic interactions. European journal of pain 2016; 20(2): 297-306. [DOI:10.1002/ejp.728]
29. Jara-Oseguera A, Simon SA, Rosenbaum T. TRPV1: on the road to pain relief. Current molecular Pharmacol 2008; 1(3): 255-269. [DOI:10.2174/1874467210801030255]
30. Chen Y, Geis C, Sommer C. Activation of TRPV1 contributes to morphine tolerance. Journal of neuroscience 2008; 28(22): 5836-5845. [DOI:10.1523/JNEUROSCI.4170-07.2008]
31. Vardanyan A, Wang R, Vanderah TW, Ossipov MH, Lai J, Porreca F, King T. TRPV1 receptor in expression of opioid-induced hyperalgesia. The journal of pain 2009; 10(3): 243-252. [DOI:10.1016/j.jpain.2008.07.004]
32. Sasamura T, Sasaki M, Tohda C, Kuraishi Y. Existence of capsaicin-sensitive glutamatergic terminals in rat hypothalamus. Neuroreport 1998; 9(9): 2045-2048. [DOI:10.1097/00001756-199806220-00025]
33. Chen SR, Pan HL. Blocking μ opioid receptors in the spinal cord prevents the analgesic action by subsequent systemic opioids. Brain research 2006; 1081(1): 119-125. [DOI:10.1016/j.brainres.2006.01.053]
34. Endres-Becker J, Heppenstall PA, Mousa SA, Labuz D, Oksche A, Schäfer M, Stein C, Zöllner C. μ-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. Molecular pharmacology 2007; 71(1):12-18. [DOI:10.1124/mol.106.026740]
35. Shaqura M, Khalefa BI, Shakibaei M, Zöllner C, Al-Khrasani M, Fürst S, Schäfer M, Mousa SA. New insights into mechanisms of opioid inhibitory effects on capsaicin-induced TRPV1 activity during painful diabetic neuropathy. Neuropharmacology 2014; 85: 142-150. [DOI:10.1016/j.neuropharm.2014.05.026]
36. Walker KM, Urban L, Medhurst SJ, Patel S, Panesar M, Fox AJ, Mclntyre P. The VR1 antagonist capsazepine reverses mechanical hyperalgesia in models of inflammatory and neuropathic pain. Journal of pharmacology and experimental therapeutics 2003; 304(1): 56-62. [DOI:10.1124/jpet.102.042010]
37. Koda K, Hyakkoku K, Ogawa K, Takasu K, Imai S, Sakurai Y. Sensitization of TRPV1 by protein kinase C in rats with mono-iodoacetate-induced joint pain. Osteoarthritis and cartilage 2016; 24(7): 1254-1262. [DOI:10.1016/j.joca.2016.02.010]
38. Premkumar LS, Ahern GP. Induction of vanilloid receptor channel activity by protein kinase C. Nature 2000; 408(6815): 985-990. [DOI:10.1038/35050121]
39. Vellani V, Mapplebeck S, Moriondo A, Davis JB, McNaughton PA. Protein kinase C activation potentiates gating of the vanilloid receptor VR1 by capsaicin, protons, heat and anandamide. The journal of physiology 2001; 534(3): 813-825. [DOI:10.1111/j.1469-7793.2001.00813.x]
40. Mohapatra DP, Nau C. Desensitization of capsaicin-activated currents in the vanilloid receptor TRPV1 is decreased by the cyclic AMP-dependent protein kinase pathway. Journal of biological chemistry 2003; 278(50): 50080-50090. [DOI:10.1074/jbc.M306619200]
41. Moriyama T. Sensitization of TRIPV1 by EP1 and IP reveals peripheral nociceptive mechanism of prostaglandins. BMC molecular pain 2005; 1: 1-13. [DOI:10.1186/1744-8069-1-3]
42. Casanova E, Guetg N, Vigot R, Seddik R, Julio-Pieper M, Hyland NP, Cryan JF, Gassmann M, Bettler B. A mouse model for visualization of GABAB receptors. Genesis 2009; 47(9): 595-602. [DOI:10.1002/dvg.20535]

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