The Korean Journal of Pain

The Korean Pain Society (대한통증학회)
권호 표지

Potentiation of Morphine's Antinociception by Group II and Group III Metabotropic Glutamate Receptors Agonists on a Rat Incisional Pain

  • Kim, Chang Mo (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Choi, Jeong Il (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Bae, Hong Beom (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Kim, Seok Jai (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Chung, Sung Tae (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Kim, Ok Hwan (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School) ;
  • Yoon, Myung Ha (Department of Anesthesiology and Pain Medicine, Chonnam National University Medical School)
  • Received : 2006.07.12
  • Accepted : 2006.09.18
  • Published : 2006.12.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: The aim of this study was to clarify the role of spinal groups II and III metabotropic glutamate receptors (mGluRs) with respect to postoperative pain at the spinal level. In addition, the nature of the pharmacological interaction between groups II and III mGluRs agonists and morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. To induce postoperative pain, an incision was made in the plantar surface of the hind paw. A pharmacological characteristic for the interaction between groups II and III mGluRs agonists and morphine was evaluated using a fixed-dose analysis. Results: None of intrathecal group II and III mGluRs agonists modified the withdrawal threshold of the incisional pain. The administration of intrathecal morphine resulted in an increase of a dose dependent withdrawal threshold. A fixed-dose analysis revealed that the group III mGluRs agonist, ACPT-III, increased the antinociceptive action of morphine, while the group II mGluRs agonist, APDC, had no effect the antinociception of morphine. Conclusions: These results suggest that group II and III mGluRs may not play a direct modulatory role in the processing of postoperative pain at the spinal level. However, agonizing group III mGluRs may indirectly contributable to the potentiation of morphines antinociception in the spinal cord. Thus, the combination of morphine and a group III mGluRs agonist may be useful in the management of spinal postoperative pain.

Keywords

References

  1. Woolf CJ, Chong MS: Preemptive analgesia treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993; 77: 362-79 https://doi.org/10.1213/00000539-199377020-00026
  2. Ji RR, Woolf CJ: Neuronal plasticity and signal transduction in nociceptive neurons: implications for the initiation and maintenance of pathological pain. Neurobiol Dis 2001; 8: 1-10 https://doi.org/10.1006/nbdi.2000.0360
  3. Neugebauer V: Metabotropic glutamate receptors-important modulators of nociception and pain behavior. Pain 2002; 98: 1-8 https://doi.org/10.1016/S0304-3959(02)00140-9
  4. Conn PJ, Pin JP: Pharmacology and functions of metabotropic glutamate receptors. Annu Rev Pharmacol Toxicol 1997; 37: 205-37 https://doi.org/10.1146/annurev.pharmtox.37.1.205
  5. Varney MA, Gereau RW 4th: Metabotropic glutamate receptor involvement in models of acute and persistent pain: prospects for the development of novel analgesics. Curr Drug Targets CNS Neurol Disord 2002; 1: 283-96 https://doi.org/10.2174/1568007023339300
  6. Dolan S, Kelly JG, Monteiro AM, Nolan AM: Differential expression of central metabotropic glutamate receptor (mGluR) subtypes rn a clinical model of post-surgical pain. Pain 2004; 110: 369-77 https://doi.org/10.1016/j.pain.2004.04.018
  7. Yaksh TL, Rudy TA: Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976; 17: 1031-6 https://doi.org/10.1016/0031-9384(76)90029-9
  8. Brennan TJ, Vandermeulen EP, Gebhart GF: Characterization of a rat model of incisional pain. Pain 1996; 64: 493-501 https://doi.org/10.1016/0304-3959(95)01441-1
  9. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 55-63 https://doi.org/10.1016/0165-0270(94)90144-9
  10. Dickenson AH, Chapman V, Green GM: The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord. Gen Pharmacol 1997; 28: 633-8 https://doi.org/10.1016/S0306-3623(96)00359-X
  11. Baranauskas G, Nistri A: Sensitization of pain pathways in the spinal cord: cellular mechanisms. Prog Neurobiol 1998; 54: 349-65 https://doi.org/10.1016/S0301-0082(97)00067-1
  12. Aanonsen LM, Lei S, Wilcox GL: Excitatory amino acid receptors and nociceptive neurotransmission in rat spinal cord. Pain 1990; 41:309-21 https://doi.org/10.1016/0304-3959(90)90008-2
  13. Cumberbatch MJ, Chizh BA, Headley PM: Modulation of excitatory amino acid responses by tachykinins and selective tachykinin receptor agonists in the rat spinal cord. Br J Pharmacol 1995; 115: 1005-12 https://doi.org/10.1111/j.1476-5381.1995.tb15911.x
  14. Ohishi H, Shigemoto R, Nakanishi S, Mizuno N: Distribution of the mRNA for a metabotropic glutamate receptor (mGluR3) in the rat brain: an in situ hybridization study. J Comp Neurol 1993; 335: 252-66 https://doi.org/10.1002/cne.903350209
  15. Valerio A, Paterlini M, Boifava M, Memo M, Spano P: Metabotropic glutamate receptor mRNA expression in rat spinal cord. Neuroreport 1997; 8: 2695-9 https://doi.org/10.1097/00001756-199708180-00012
  16. Azkue JJ, Murga M, Fernandez-Capetillo O, Mateos JM, Elezgarai I, Benitez R, et al: Immunoreactivity for the group IIImetabotropic glutamate receptor subtype mGluR4a in the superficial laminae of the rat spinal dorsal horn. J Comp Neurol 2001; 430: 448-57 https://doi.org/10.1002/1096-9861(20010219)430:4<448::AID-CNE1042>3.0.CO;2-O
  17. Ohishi H, Nomura S, Ding YQ, Shigemoto R, Wada E, Kinoshita A, et al: Presynaptic localization of a rnetabotropic glutamate receptor, mGluR7, in the primary afferent neurons an immunohistochemical study in the rat. Neurosci Lett 1995; 202: 85-8 https://doi.org/10.1016/0304-3940(95)12207-9
  18. Nishizuka Y: Studies and perspectives of protein kinase C. Science 1986; 233: 305-12 https://doi.org/10.1126/science.3014651
  19. Yashpal K, Pitcher GM, Parent A, Quirion R, Coderre TJ: Noxious thermal and chemical stimulation induce increases in 3H-phorbol 12, 13-dibutyrate binding in spinal cord dorsal horn as well as persistent pain and hyperalgesia, which is reduced by inhibition of protein kinase C. J Neurosci 1995; 15: 3263-72 https://doi.org/10.1523/JNEUROSCI.15-05-03263.1995
  20. Yamamoto T, Hirasawa S, Wroblewska B, Grajkowska E, Zhou J, Kozikowski A, et al: Antinociceptive effects of N-acetylaspartylglutamate (NAAG) peptidase inhibitors ZJ-11, ZJ-17 and ZJ-43 in the rat formalin test and in the rat neuropathic pain model. Eur J Neurosci 2004; 20: 483-94 https://doi.org/10.1111/j.1460-9568.2004.03504.x
  21. Fisher K, Lefebvre C, Coderre TJ: Antinociceptive effects following intrathecal pretreatment with selective metabotropic gluramate receptor compounds in a rat model of neuropathic pain. Pharmacol Biochem Behav 2002; 73: 411-8 https://doi.org/10.1016/S0091-3057(02)00832-8
  22. Fisher K, Coderre TJ: The contribution of metabotropic glutamate receptors (mGluRs) to formalin-induced nociception. Pain 1996; 68:255-63 https://doi.org/10.1016/S0304-3959(96)03212-5
  23. Zahn PK, Gysbers D, Brennan TJ: Effect of systemic and intrathecal morphine in a rat model of postoperative pain. Anesthesiology 1997; 86: 1066-77 https://doi.org/10.1097/00000542-199705000-00010
  24. Berenbaum MC: What is synergy? Pharmacol Rev 1989; 41: 93-141
  25. Malmberg AB, Yaksh TL: Pharmacology of the spinal action of ketorolac, morphine, ST-91, U50488H, and L-PIA on the formalin test and an isobolographic analysis of the NSAID interaction. Anesthesiology 1993; 79: 270-81 https://doi.org/10.1097/00000542-199308000-00012