Browse > Article

N-methyl-D-aspartate (NMDA) and Non-NMDA Receptors are Involved in the Production and Maintenance of Nociceptive Responses by Intraplantar Injection of Bee Venom and Melittin in the Rat  

Kim, Jae-Hwa (Department of Orthopaedic Surgery, Bundang Cha Hospital, College of Medicine, Pochun Cha University)
Shin, Hong-Kee (Deportment of Physiology, College of Medicine, Hanyang University)
Publication Information
The Korean Journal of Physiology and Pharmacology / v.9, no.3, 2005 , pp. 179-186 More about this Journal
Abstract
Whole bee venom (WBV) and its major component, melittin, have been reported to induce long-lasting spontaneous flinchings and hyperalgesia. The current study was designed to elucidate the peripheral and spinal mechanisms of N-methyl-D-aspartate (NMDA) and non-NMDA receptors by which intraplantar (i.pl.) injection of WBV and melittin induced nociceptive responses. Changes in mechanical threshold and flinching behaviors were measured after the injection of WBV (0.04 mg or 0.1 mg/paw) and melittin (0.02 mg or 0.05 mg/paw) into the mid-plantar area of a rat hindpaw. MK-801 and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione disodium) were administered intrathecally (i.t. $10{\mu}g$) or i.pl.($15{\mu}g$) 15 min before or i.t. 60 min after i.pl. WBV and melittin injection. Intrathecal pre- and postadministration of MK-801 and CNQX significantly attenuated the ability of high dose WBV and melittin to reduce paw withdrawal threshold (PWT). In the rat injected with low dose, but not high dose, of WBV and melittin, i.pl. injection of MK-801 effectively suppressed the decrease of PWTs only at the later time-points, but the inhibitory effect of CNQX (i.pl.) was significant at all time-point after the injection of low dose melittin. High dose WBV- and melittin-induced spontaneous flinchings were significantly suppressed by i.t. administration of MK-801 and CNQX, and low dose WBV- and melittin-induced flinchings were significantly reduced only by intraplantarly administered CNQX, but not by MK-801. These experimental flinchings suggest that spinal, and partial peripheral mechanisms of NMDA and non-NMDA receptors are involved in the development and maintenance of WBV- and melittin-induced nociceptive responses.
Keywords
Whole bee venom; Melittin; Paw withdrawal threshold; Spontaneous flinching; NMDA and non-NMDA receptors;
Citations & Related Records

Times Cited By SCOPUS : 5
연도 인용수 순위
1 Chen L, Mae Huang L-Y. Sustained potentiation of NMDA receptor-mediated glutamate responses through activation of protein kinase C by a opioid. Neuron 7: 319-326, 1991   DOI   ScienceOn
2 Kim YI, Na HS, Yoon YW, Han HC, Ko KH, Hong SK. NMDA receptors are important for both mechanical and thermal allodynia from peripheral nerve injury in rats. Neuroreport 8: 2149-2153, 1997   DOI   PUBMED   ScienceOn
3 Lariviere WR, Melzack R. The bee venom test: a new tonic pain test. Pain 66: 271-277, 1996   DOI   PUBMED   ScienceOn
4 Li K-C, Chen J. Altered pain-related behaviors and spinal neuronal responses produced by s.c. injection of melittin in rats. Neuroscience 126: 753-762, 2004   DOI   ScienceOn
5 Manseau F, Sossion WS, Castellucci VF. Long-term changes in excitability induced by protein kinase C activation in Aplysia sensory neurons. J Neurophysiol 79: 1210-1218, 1998   PUBMED
6 Neugebauer V, Lcke T, Schaible H-G. N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists block the hyperexcitability of dorsal horn neurons during development of acute arthritis in rat's knee joint. J Neurophysiol 70: 1365-1377, 1993   DOI   PUBMED
7 Omote K, Kawamata T, Kawamata M, Namiki A. Formalin-induced release of excitatory amino acids in the skin of the rat hindpaw. Brain Res 787: 161-164, 1998   DOI   ScienceOn
8 Schneider SP, Perl ER. Comparison of primary afferent and glutamate excitation of neurons in the mammalian spinal dorsal horn. J Neurosci 8: 2062-2073, 1988   PUBMED
9 Sluka KA, Westlund KN. An experimental arthritis model in rats: the effects of NMDA and non-NMDA antagonists on aspartate and glutamate release in the dorsal horn. Neurosci Lett 149: 99- 102, 1993   DOI   ScienceOn
10 Westlund KN, Sun YC, Sluka KA, Dougherty PM, Sorkin LS, Willis WD. Neuronal changes in acute arthritis in monkeys. II. Increased glutamate immunoreactivity in the medial articular nerve. Brain Res Rev 17: 15-27, 1992   DOI   ScienceOn
11 Zheng JH, Chen J. Modulatory roles of the adenosine triphosphate P2x-purinoceptor in generation of the persistent nociception induced by subcutaneous bee venom injection in the conscious rat. Neurosci Lett 278: 41-44, 2000   DOI   PUBMED   ScienceOn
12 Zheng JH, Chen J. Differential roles of spinal neurokinin 1/2 receptors in development of persistent spontaneous nociception and hyperalgesia induced by subcutaneous bee venom injection in the conscious rat. Neuropeptide 35: 32-44, 2001   DOI   ScienceOn
13 Carlton SM, Coggeshall RE. Inflammation-induced changes in peripheral glutamate receptor populations. Brain Res 820:63- 70, 1999   DOI   PUBMED   ScienceOn
14 Chen J, Li H-L, Luo C, Li Z, Zheng J-H. Involvement of peripheral NMDA and non-NMDA receptors in development of persistent firing of spinal wide-dynamic-range neurons induced by subcutaneous bee venom injection in the cat. Brain Res 844: 98-105, 1999a   DOI   PUBMED   ScienceOn
15 Chen HS, Chen J, Sun YY. Contralateral heat hyperalgesia induced by unilaterally intraplantar bee venom injection is produced by central changes: a behavioral study in the conscious rat. Neurosci Lett 284: 45-48, 2000   DOI   PUBMED   ScienceOn
16 Calixto MC, Triches KM, Calixto JB. Analysis of the inflammatory response in the rat paw caused by the venom of Apis melifera bee. Inflam Res 52: 132-139, 2003   DOI   ScienceOn
17 Lee KH, Shin HK, Kim JS, Kim JH. Effects of intrathecal and intraplantar injection of calcium channel antagonists on melittin-induced mechanical hyperalgesia in rats. Kor J Physiol Pharmacol 8(Suppl. I): S133, 2004
18 Kwon YB, Kim JH, Yoon JH, Lee JD, Han HJ, Mar WC, Beitz AJ. The analgesic efficacy of bee venom acupuncture for knee osteoarthritis: a comparative study with needle acupuncture. Am J Chin Med 29: 187-199, 2001   DOI   ScienceOn
19 Ong WY, Horrocks LA, Farooqui AA. Immunocytochemical localization of $cPLA_{2}$ in rat and monkey spinal cord. J Mol Neurosci 12: 123-130, 1999   DOI   ScienceOn
20 Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Meth 53: 55-63, 1994   DOI   ScienceOn
21 Kwon YB, Kang MS, Han HJ, Beitz AJ, Lee JH. Visceral antinociception produced by bee venom stimulation of the Zhongwan acupuncture point in mice: role of $\alpha_{2}$ adrenoceptors. Neurosci Lett 308: 133-137, 2001   DOI   PUBMED   ScienceOn
22 Habermehl GG. Venomous animals and their toxins. 1st ed. Springer-Verlag, New York, p 476, 1981
23 Mao J, Price DD, Phillips LL, Lu J, Mayer DJ. Increase in protein kinase C gamma immunoreactivity in the spinal cord dorsal horn of rats with painful mononeuropathy. Neurosci Lett 198: 75-78, 1995   DOI   ScienceOn
24 Shin HK, Kim JH. Melittin selectively activates capsaicin-sensitive primary afferent fibers. Neuroreport 15: 1745-1749, 2004   DOI   ScienceOn
25 Haley JE, Sullivan AF, Dickenson AH. Evidence for spinal Nmethyl- D-aspartate receptor involvement in prolonged chemical nociception in the rat. Brain Res 518: 218-226, 1990   DOI   ScienceOn
26 Merighi A, Polak JM, Theodosis DT. Ultrastructural visualization of glutamate and aspartate immunoreactivities in the rat dorsal horn, with special reference to the co-localization of glutamate, substance P and calcitonin gene-related peptide. Neuroscience 40: 67-80, 1991   DOI   ScienceOn
27 Paleckova V, Paleck J, McAdoo DJ, Willis WD. The non-NMDA antagonist CNQX prevents release of amino acids into the rat spinal cord dorsal horn evoked by sciatic nerve stimulation. Neurosci Lett 148: 19-22, 1992   DOI   PUBMED   ScienceOn
28 Sladeczek F, Pin J-P, Rcasens M, Bockaert J, Weiss S. Glutamate stimulates inositol phosphate formation in striatal neurones. Nature 317: 717-719, 1985   DOI   ScienceOn
29 Barber LA, Vasko MR. Activation of protein kinase C augments peptide release from rat sensory neurons. J Neurochem 67: 72- 80, 1996   DOI   PUBMED   ScienceOn
30 De Biasi S, Rustioni A. Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord. Proc Natl Acad Sci USA 85: 7820-7824, 1988   DOI
31 Chen J, Luo C, Li H-L. The contribution of spinal neuronal changes to development of prolonged, tonic nociceptive responses of the cat induced by subcutaneous bee venom injection. Europ J Pain 2: 359-376, 1998   DOI   ScienceOn
32 Li K-C, Zheng J-H, Chen J. Involvement of spinal protein kinase C in induction and maintenance of both persistent spontaneous flinching reflex and contralateral heat hyperalgesia induced by subcutaneous bee venom in the conscious rat. Neurosci Lett 285: 103-106, 2000   DOI   ScienceOn
33 Shin HK, Kim JS, Lee SE, Jun JH. Comparative study on the nociceptive responses induced by whole bee venom and melittin. Kor J Physiol Pharmacol 8: 281-288, 2004
34 Chen H-S, Li M-M, Shi J, Chen J. Supraspinal contribution to development of both tonic nociception and referred mirror hyperalgesia. Anesthesiology 98: 1231-1236, 2003   DOI   ScienceOn
35 Jeftinija S, Jeftinija K, Liu F, Skilling SR, Smullin DH, Larson AA. Excitatory amino acids are released from rat primary afferent neurons in vitro. Neurosci Lett 125: 191-194, 1991   DOI   ScienceOn
36 Lee JH, Kwon YB, Han HJ, Mar WC, Lee HJ, Yang IS, Beitz AJ, Kang SK. Bee venom pretreatment has both an antinociceptive and anti-inflammatory effect on carrageenan-induced inflammation. J Vet Med Sci 63: 251-259, 2001   DOI   ScienceOn
37 Ren K, Hylden JLK, Williams GM, Ruda MA, Dubner R. The effects of a non-competitive NMDA receptor antagonist, MK-801, on behavioral hyperalgesia and dorsal horn neuronal activity in rats with unilateral inflammation. Pain 50: 331-334, 1992   DOI   ScienceOn
38 Luo C, Chen J, Li HL, Li J-H. Spatial and temporal expression of C-Fos protein in the spinal cord of anesthetized rat induced by subcutaneous bee venom injection. Brain Res 806: 175-185, 1998   DOI   ScienceOn
39 Raigorodsky G, Urca G. Intrathecal N-methyl-D-aspartate (NMDA) activates both nociceptive and antinociceptive systems. Brain Res 422: 158-162, 1987   DOI   ScienceOn
40 Yang J, Tsien RV. Enhancement of N- and L-type calcium channel currents by protein kinase C in frog sympathetic neurons. Neuron 10: 127-136, 1993   DOI   ScienceOn
41 Luttinger D. Determination of antinociceptive efficacy of drugs in mice using different water temperatures in a tail-immersion test. J Pharmacol Meth 13: 351-357, 1985   DOI   PUBMED   ScienceOn
42 Lawand NB, Willis WD, Westlund KN. Excitatory amino acid receptor involvement in peripheral nociceptive transmission in rats. Europ J Pharmacol 324: 169-177, 1997   DOI   ScienceOn
43 Chen J, Chen H-J. Pivotal role of capsaicin-sensitive primary afferents in development of both heat and mechanical hyperalgesia induced by intraplantar bee venom injection. Pain 91: 367-376, 2000
44 Coderre TJ. Contribution of protein kinase C to central sensitization and persistent pain following tissue injury. Neurosci Lett 140: 181-184, 1992   DOI   PUBMED   ScienceOn
45 Davidson EM, Coggeshall RE, Carlton SM. Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test. Neuroreport 8: 941-946, 1997   DOI   PUBMED   ScienceOn
46 Sluka KA, Jordan HH, Willis WD, Westlund KN. Differential effects of N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists on spinal release of amino acids after development of acute arthritis in rats. Brain Res 664: 77-84, 1994   DOI   PUBMED   ScienceOn
47 deGroot J, Zhou S, Carlton SM. Peripheral glutamate release in the hindpaw following low and high intensity sciatic stimulation. Neuroreport 11: 497-502, 2000   DOI   PUBMED   ScienceOn
48 Chen J, Luo C, Li H-L, Chen H-S. Primary hyperalgesia to mechanical and heat stimuli following subcutaneous bee venom injection into the plantar surface of hindpaw in the conscious rat: a comparative study with the formalin test. Pain 83: 67-76, 1999b   DOI   ScienceOn
49 Mayer ML, MacDermott AB, Westbrook GL, Smith SJ, Barker JL. Agonist- and voltage-gated calcium entery in cultured mouse spinal cord neurons under voltage clamp measured using arsenazo III. J Neurosci 7: 3230-3244, 1987   PUBMED
50 Curtis DR, Phillis JW, Watkins JC. Chemical excitation of spinal neurones. Nature 183: 611-612, 1959   DOI   ScienceOn
51 You H-J, Chen J. Differential effects of subcutaneous injection of formalin and bee venom on responses of wide-dynamic-range neurons in spinal dorsal horn of the rat. Europ J Pain 3: 177- 180, 1999   DOI   ScienceOn
52 Schneider SP, Perl ER. Selective excitation of neurons in the mammalian spinal dorsal horn by aspartate and glutamate in vitro: correlation with location and excitatory input. Brain Res 360: 339-343, 1985   DOI   PUBMED   ScienceOn
53 Mao J, Price DD, Hayes RL, Lu J, Mayer DJ. Differential roles of NMDA and non-NMDA receptor activation in induction and maintenance of thermal hyperalgesia in rats with painful peripheral mononeuropathy. Brain Res 598: 271-278, 1992   DOI   PUBMED   ScienceOn
54 You H-J, Chen J, Morch CD, Arendt-Nielsen L. Differential effect of peripheral glutamate (NMDA, non-NMDA) receptor antagonist on bee venom-induced spontaneous nociception and sensitization. Brain Res Bull 58: 561-567, 2002   DOI   ScienceOn
55 Zhou S, Bonasera L, Carlton SM. Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats. Neuroreport 7: 895-900, 1996   DOI   PUBMED   ScienceOn