Multiple 5-Hydroxytryptamine (5-HT) Receptors Are Involved in the Melittin-induced Nociceptive Responses in Rat I. Role of Peripheral 5-HT Receptor

다국어 초록 (Multilingual Abstract)

Melittin-induced tonic pain model is characterized by local inflammation, edema, spontaneous flinchings, and sustained mechanical hypersensitivity. These nociceptive responses are mediated through selective activation of capsaicin-sensitive primary afferent fibers by melittin. The present study was undertaken to elucidate the role of peripheral 5-hydroxytryptamine (5-HT) receptors in the melittin-induced nociceptive responses. Changes in mechanical threshold, flinching behaviors and paw thickness were measured in rat intraplantarly injected with melittin (40μg/paw) alone or treated together with melittin and 5-HT receptor antagonists. WAY-100635 (100μg & 200μg/paw), isamoltane hemifumarate (100μg & 200μg/paw), methysergide maleate (60μg, 120μg & 200μg/paw) and ICS-205,930 (100μg & 200μg/paw) were intraplantarly injected 20 min before melittin injection. All 5-HT receptor antagonists tested in this experiment significantly attenuated the ability of melittin to reduce mechanical threshold and to induce flinching behaviors. 5-HT receptor antagonists, except ICS-205,930, had mild inhibitory effect on melittin-induced edema. These experimental findings suggest that multiple peripheral 5-HT receptors are involved in the melittin-induced nociceptive responses.

참고문헌 (Reference)

1 Shefner SA, "an intracellular study in bullfrog dorsal root ganglion" 1985

2 Cardenas CG, "Variation in serotonergic inhibition of calcium channel currents in four types of rat sensory neurons differentiated by membrane properties" 74 : 1870-1879, 1995

3 Zhang YQ, "The role of 5-hydoxytryptamine 1A and 5-hydroxytryptamine 1B receptors in modulating spinal nociceptive transmission in normal and carrageenan-injected rats" 92 : 201-211, 2001

4 Molokanova EA, "The effects of dopamine and serotonin on rat dorsal root ganglion neurons: an intracellular study" 65 : 859-867, 1995

5 Wei H, "The contribution of peripheral 5-hydroxytryptamine 2A receptor to carrageenan-evoked hyperalgesia, inflammation and spinal fos protein expression in the rat" 132 : 1073-1082, 2005

6 Dumuis A, "The 5-HT4 receptor subtype inhibits K+ current in colliculi neurons via activation of a cyclic AMP-dependent protein kinase" 1992

7 Zeitz KP, "The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors" 22 : 1010-1019, 2002

8 Luo C, "Spatial and temporal expression of c-Fos protein in the spinal cord of anesthetized rat induced by subcutaneous bee venom injection" 806 : 175-185, 1998

9 Xu W, "Serotonin receptor subtypes in spinal antinociception in the rat" 1994

10 Nicholson R, "Serotonin receptor mRNA expression in rat dorsal root ganglion neurons" 337 : 119-122, 2003

11 Taiwo YO, "Serotonin is a directly-acting hyperalgesic agent in the rat" -48, 1992

12 Cardenas CG, "Serotonin inhibits high-threshold Ca2+ channel currents in capsaicin-sensitive acutely isolated adult rat DRG neurons" Del Mar LP 1994

13 Siegelbaum SA, "Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones" -299, 1982

14 "Role of voltage-dependent calcium channel subtypes in experimental tactile allodynia" chaplan sr : 1994

15 Schomburg FM, "Receptor mediation of 5-HT-induced inflammation and nociception in rats" 1991

16 Klein M, "Presynaptic modulation of voltage-dependent Ca2+ current mechanism for behavioral sensitization in Aplysia california" 1978

17 Anderson EG, "Pharmacological characterization of 5-hydoxytryptamine 2 and 5-hydroxytryptamine 3 receptors in rat dorsal root ganglion cells" 1990a

18 Abbott FV, "Persisting sensitization of the behavioral response to formalin-induced injury in the rat through activation of serotonin2A receptors" 77 : 575-584, 1997

19 Sasaki M, "Peripheral 5-HT2A receptor antagonism attenuates primary thermal hyperalgesia and secondary mechanical allodynia after thermal injury in rats" 122 : 130-136, 2006

20 Kim JH, "N-methyl-D-aspartate 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" 9 : 179-186, 2005

21 Chen JJ, "Multiple subtypes of serotonin receptors are expressed in rat sensory neurons in culture" 287 : 1119-1127, 1998

22 Kim J, "Melittin-induced nociceptive responses are alleviated by cyclooxygenase 1 inhibitor" 10 : 4550-, 2006

23 Shin HK, "Melittin selectively activates capsaicin-sensitive primary afferent fibers" 15 : 1745-1749, 2004

24 Taiwo YO, "Mediation of serotonin hyperalgesia by the cAMP second messenger system" -48, 1992

25 Doi-Saika M, "Intradermal 5-HT induces Fos expression in the rat dorsal horn neurons not via 5-HT3 but via 5-HT2A receptors" 29 : 143-149, 1997

26 Carlton SM, "Immunohistochemical localization of 5-HT2A receptors in peripheral sensory axons in rat glabrous skin" 763 : 271-275, 1997

27 Gold MS, "Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors" 93 : 1108-1112, 1996

28 Doak GJ, "Formalin-induced nociceptive behavior and edema: Involvement of multiple peripheral 5-hydroxytryptamine receptor subtype" 80 : 939-949, 1997

29 Mense S, "Excitatory effects of 5-hydroxytryptamine histamine and potassium ions on muscular group IV afferent units A comparison with bradykinin" 1976

30 Chen YN, "Effects of bee venom peptidergic components on rat pain-related behaviors and inflammation" 138 : 631-640, 2006

31 Millan MJ, "Descending control of pain" 66 : 355-474, 2002

32 Nitanda A, "Contribution of the peripheral 5-HT2A receptor to mechanical hyperalgesia in a rat model of neuropathic pain" 47 : 394-400, 2005

33 Shin HK, "Comperative study on the nociceptive responses induced by whole bee venom and melittin" 8 : 281-288, 2004

34 Wu SX, "Changes of the expression of 5-HT receptor subtype mRNAs in rat dorsal root ganglion by complete Freund's adjuvant-induced inflammation" 307 : 183-186, 2001

35 Liu XY, "Changes of 5-HT receptor subtype mRNAs in rat dorsal root ganglion by bee venom-induced inflammatory pain" 375 : 42-46, 2005

36 Shin HK, "Calcium ions are involved in modulation of melittin-induced nociception in rat: II" 10 : 297-302, 2006

37 Shin HK, "Calcium ions are involved in modulation of melittin-induced nociception in rat: I. Effect of voltage-gated calcium channel antagonist" 10 : 255-261, 2006

38 Calixto MC, "Analysis of the inflammatory responses in the rat paw caused by the venom of Apis melifera bee" 52 : 132-139, 2003

39 Li KC, "Altered pain-related behaviors and spinal neuronal responses produced by s.c. injection of melittin in rats" 126 : 753-762, 2004

40 Yu YQ, "Activation of spinal extracellular signaling-regulated kinases by intraplantar melittin injection" 381 : 194-198, 2005

41 Herbert MK, "Activation of normal and inflamed fine articular afferent units by serotonin" 1992

42 Wang W, "5-hydroxytryptamine 1A receptor is involved in the bee venom induced inflammatory pain" 106 : 135-142, 2003

43 Rueff A, "5-Hydroxytryptamine-induced sensitization and activation of peripheral fibers in the neonatal rat are mediated via different 5-hydroxytryptamine receptors" -50, 1992

44 Pierce PA, "5-Hydroxytryptamine receptor subtype messenger RNAs in rat peripheral sensory and sympathetic ganglia: A polymerase chain reaction study" 70 : 553-559, 1996

45 Nakano T, "5-Hydroxytryptamine as a sensitizer of somatic nociceptors for pain-producing substances" 1976

46 Cardenas CG, "5-HT4 receptors couple positively to tetrodotoxin-insensitive sodium channels in a subpopulation of capsaicin-sensitive rat sensory neurons" 17 : 7181-7189, 1997

47 Tokunaga A, "5-HT2A receptor subtype is involved in the thermal hyperalgesic mechanism of serotonin in the periphery" 76 : 349-355, 1998

48 Okamoto K, "5-HT2A receptor subtype in the peripheral branch of sensory fibers is involved in the potentiation of inflammatory pain in rats" 99 : 133-143, 2002

49 Anderson EG, "5-HT2 and 5-HT3 receptors mediate two distinct depolarizing responses in rat dorsal root ganglion neurons" 1990b

50 Cardenas LM, "5-HT increases excitability of nociceptor-like rat dorsal root ganglion neurons via cAMP-coupled TTX-resistant Na+ channels" 86 : 241-248, 2001