The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
권호 표지
DOI QR코드

DOI QR Code

The Effects of Pre-emptive Administration of Ketamine and norBNI on Pain Behavior, c-Fos, and Prodynorphin Protein Expression in the Rat Spinal Cord after Formalin-induced Pain Is Modulated by the DREAM Protein

  • Long, Idris (BRAINetwork Centre for Neurocognitive Science, School of Health Sciences, Health Campus, Universiti Sains Malaysia) ;
  • Suppian, Rapeah (BRAINetwork Centre for Neurocognitive Science, School of Health Sciences, Health Campus, Universiti Sains Malaysia) ;
  • Ismail, Zalina (BRAINetwork Centre for Neurocognitive Science, School of Health Sciences, Health Campus, Universiti Sains Malaysia)
  • Received : 2013.04.09
  • Accepted : 2013.05.28
  • Published : 2013.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection. Methods: Eighty-four male Sprague Dawley rats were divided into 4 major groups consisting of control rats (C) (n = 12), rats given only formalin injections (F) (n = 24), and rats treated with pre-emptive administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The non-control groups were further divided into subgroups consisting of rats that were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats were sacrificed and the spinal cords (L4-L5 sections) were removed for immunohistochemistry and Western blot analysis. Results: The pain behavior response was reduced in the K+F group compared to the other groups during the second phase of the formalin pain response. We detected an increase in the nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient decrease in the N+F group at 2 hours; however, it increased at 4 hours after injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity (PLI) neurons decreased in the K+F group but increased in the N+F group at 2 hours after injection. While FLI decreased, PLI increased in all groups at 4 hours after injection. Conclusions: We suggest that NMDA and kappa opioid receptors can modulate DREAM protein expression, which can affect pain behavior and protein transcriptional processes at 2 hours and bring about either harmful or protective effects at 4 hours after formalin injection.

Keywords

References

  1. Carrion AM, Link WA, Ledo F, Mellstrocm B, Naranjo JR. DREAM is a Ca2+-regulated transcriptional repressor. Nature 1999; 398: 80-4. https://doi.org/10.1038/18044
  2. Cheng HY, Pitcher GM, Laviolette SR, Whishaw IQ, Tong KI, Kockeritz LK, et al. DREAM is a critical transcriptional repressor for pain modulation. Cell 2002; 108: 31-43. https://doi.org/10.1016/S0092-8674(01)00629-8
  3. Lilliehook C, Bozdagi O, Yao J, Gomez-Ramirez M, Zaidi NF, Wasco W, et al. Altered Abeta formation and long-term potentiation in a calsenilin knock-out. J Neurosci 2003; 23: 9097-106.
  4. Obara I, Mika J, Schafer MK, Przewlocka B. Antagonists of the kappa-opioid receptor enhance allodynia in rats and mice after sciatic nerve ligation. Br J Pharmacol 2003; 140: 538-46. https://doi.org/10.1038/sj.bjp.0705427
  5. Sevostianova N, Danysz W, Bespalov AY. Analgesic effects of morphine and loperamide in the rat formalin test: interactions with NMDA receptor antagonists. Eur J Pharmacol 2005; 525: 83-90. https://doi.org/10.1016/j.ejphar.2005.10.010
  6. Snijdelaar DG, van Rijn CM, Vinken P, Meert TF. Effects of pre-treatment with amantadine on morphine induced antinociception during second phase formalin responses in rats. Pain 2005; 119: 159-67. https://doi.org/10.1016/j.pain.2005.09.027
  7. Fukuda T, Nishimoto C, Shiga Y, Toyooka H. The formalin test: effects of formalin concentration and short-term halothane inhalation. Reg Anesth Pain Med 2001; 26: 407-13.
  8. Lee IO, Jeong YS. Effects of different concentrations of formalin on paw edema and pain behaviors in rats. J Korean Med Sci 2002; 17: 81-5. https://doi.org/10.3346/jkms.2002.17.1.81
  9. Kim MJ, Hong BH, Zhang EJ, Ko YK, Lee WH. Antinociceptive effects of intraperitoneal and intrathecal vitamin E in the rat formalin test. Korean J Pain 2012; 25: 238-44. https://doi.org/10.3344/kjp.2012.25.4.238
  10. Hayati AA, Zalina I, Myo T, Badariah AA, Azhar A, Idris L. Modulation of formalin-induced fos-like immunoreactivity in the spinal cord by swim stress-induced analgesia, morphine and ketamine. Ger Med Sci 2008; 6: Doc05.
  11. Grossman A, Clement-Jones V. Opiate receptors: enkephalins and endorphins. Clin Endocrinol Metab 1983; 12: 31-56. https://doi.org/10.1016/S0300-595X(83)80028-0
  12. Horan P, Taylor J, Yamamura HI, Porreca F. Extremely longlasting antagonistic actions of nor-binaltorphimine (nor-BNI) in the mouse tail-flick test. J Pharmacol Exp Ther 1992; 260: 1237-43.
  13. Spanagel R, Almeida OF, Shippenberg TS. Evidence that nor-binaltorphimine can function as an antagonist at multiple opioid receptor subtypes. Eur J Pharmacol 1994; 264: 157-62. https://doi.org/10.1016/0014-2999(94)00449-8
  14. Endoh T, Matsuura H, Tanaka C, Nagase H. Nor-binaltorphimine: a potent and selective kappa-opioid receptor antagonist with long-lasting activity in vivo. Arch Int Pharmacodyn Ther 1992; 316: 30-42.
  15. Broadbear JH, Negus SS, Butelman ER, de Costa BR, Woods JH. Differential effects of systemically administered nor-binaltorphimine (nor-BNI) on kappa-opioid agonists in the mouse writhing assay. Psychopharmacology (Berl) 1994; 115: 311-9. https://doi.org/10.1007/BF02245071
  16. Dubuisson D, Dennis SG. The formalin test: a quantitative study of the analgesic effects of morphine, meperidine, and brain stem stimulation in rats and cats. Pain 1977; 4: 161-74. https://doi.org/10.1016/0304-3959(77)90130-0
  17. Hao S, Takahata O, Mamiya K, Iwasaki H. Sevoflurane suppresses noxious stimulus-evoked expression of Fos-like immunoreactivity in the rat spinal cord via activation of endogenous opioid systems. Life Sci 2002; 71: 571-80. https://doi.org/10.1016/S0024-3205(02)01704-6
  18. Molander C, Xu Q, Grant G. The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord. J Comp Neurol 1984; 230: 133-41. https://doi.org/10.1002/cne.902300112
  19. Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 1979; 76: 4350-4. https://doi.org/10.1073/pnas.76.9.4350
  20. Berrino L, Oliva P, Massimo F, Aurilio C, Maione S, Grella A, et al. Antinociceptive effect in mice of intraperitoneal N-methyl-D-aspartate receptor antagonists in the formalin test. Eur J Pain 2003; 7: 131-7. https://doi.org/10.1016/S1090-3801(02)00086-1
  21. Ossipov MH, Kovelowski CJ, Wheeler-Aceto H, Cowan A, Hunter JC, Lai J, et al. Opioid antagonists and antisera to endogenous opioids increase the nociceptive response to formalin: demonstration of an opioid kappa and delta inhibitory tone. J Pharmacol Exp Ther 1996; 277: 784-8.
  22. Coderre TJ, Fundytus ME, McKenna JE, Dalal S, Melzack R. The formalin test: a validation of the weighted-scores method of behavioural pain rating. Pain 1993; 54: 43-50. https://doi.org/10.1016/0304-3959(93)90098-A
  23. Wu HE, Hung KC, Mizoguchi H, Nagase H, Tseng LF. Roles of endogenous opioid peptides in modulation of nocifensive response to formalin. J Pharmacol Exp Ther 2002; 300: 647-54. https://doi.org/10.1124/jpet.300.2.647
  24. Choi SS, Han KJ, Lee HK, Han EJ, Suh HW. Possible antinociceptive mechanisms of opioid receptor antagonists in the mouse formalin test. Pharmacol Biochem Behav 2003; 75: 447-57. https://doi.org/10.1016/S0091-3057(03)00144-8
  25. Ikeda H, Stark J, Fischer H, Wagner M, Drdla R, Jäger T, et al. Synaptic amplifier of inflammatory pain in the spinal dorsal horn. Science 2006; 312: 1659-62. https://doi.org/10.1126/science.1127233
  26. Ledo F, Carrión AM, Link WA, Mellström B, Naranjo JR. DREAM-alphaCREM interaction via leucine-charged domains derepresses downstream regulatory element-dependent transcription. Mol Cell Biol 2000; 20: 9120-6. https://doi.org/10.1128/MCB.20.24.9120-9126.2000
  27. Zaidi NF, Thomson EE, Choi EK, Buxbaum JD, Wasco W. Intracellular calcium modulates the nuclear translocation of calsenilin. J Neurochem 2004; 89: 593-601. https://doi.org/10.1046/j.1471-4159.2004.02362.x
  28. Zhang Y, Li Y, Yang YR, Zhu HH, Han JS, Wang Y. Distribution of downstream regulatory element antagonist modulator (DREAM) in rat spinal cord and upregulation of its expression during inflammatory pain. Neurochem Res 2007; 32: 1592-9. https://doi.org/10.1007/s11064-007-9364-3
  29. Long I, Suppian R, Ismail Z. Increases in mRNA and DREAM protein expression in the rat spinal cord after formalin induced pain. Neurochem Res 2011; 36: 533-9. https://doi.org/10.1007/s11064-010-0375-0
  30. Edling Y, Ingelman-Sundberg M, Simi A. Glutamate activates c-fos in glial cells via a novel mechanism involving the glutamate receptor subtype mGlu5 and the transcriptional repressor DREAM. Glia 2007; 55: 328-40. https://doi.org/10.1002/glia.20464
  31. Chavira-Suárez E, Ramírez M, Lamas M. D-Serine/Nmethyl- D-aspartate receptor signaling decreases DNAbinding activity of the transcriptional repressor DREAM in Müller glia from the retina. Neurosci Lett 2008; 432: 121-6. https://doi.org/10.1016/j.neulet.2007.12.021
  32. Coderre TJ, Melzack R. The role of NMDA receptor-operated calcium channels in persistent nociception after formalininduced tissue injury. J Neurosci 1992; 12: 3671-5.
  33. Lee J, Kim I, Oh SR, Ko SJ, Lim MK, Kim DG, et al. Regulation of DREAM expression by group I mGluR. Korean J Physiol Pharmacol 2011; 15: 95-100. https://doi.org/10.4196/kjpp.2011.15.2.95
  34. Hunt SP, Pini A, Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature 1987; 328: 632-4. https://doi.org/10.1038/328632a0
  35. Ji RR, Befort K, Brenner GJ, Woolf CJ. ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity. J Neurosci 2002; 22: 478-85.
  36. Zhang Y, Su P, Liang P, Liu T, Liu X, Liu XY, et al. The DREAM protein negatively regulates the NMDA receptor through interaction with the NR1 subunit. J Neurosci 2010; 30: 7575-86. https://doi.org/10.1523/JNEUROSCI.1312-10.2010

Cited by

  1. Decreased MicroRNA-125a-3p Contributes to Upregulation of p38 MAPK in Rat Trigeminal Ganglions with Orofacial Inflammatory Pain vol.9, pp.11, 2014, https://doi.org/10.1371/journal.pone.0111594
  2. Involvement of glutamate receptors of the paragigantocellularis lateralis nucleus in the pain modulatory effect of 17β-estradiol in male rats pp.2240-2993, 2018, https://doi.org/10.1007/s13760-018-0998-5
  3. Minocycline attenuates the development of diabetic neuropathy by modulating DREAM and BDNF protein expression in rat spinal cord vol.18, pp.1, 2013, https://doi.org/10.1007/s40200-019-00411-4
  4. Minocycline alleviates nociceptive response through modulating the expression of NR2B subunit of NMDA receptor in spinal cord of rat model of painful diabetic neuropathy vol.20, pp.1, 2013, https://doi.org/10.1007/s40200-021-00820-4