Spinal 5-HT3 receptor activation induces behavioral hypersensitivity via a neuronal-glial-neuronal signaling cascade

Journal of Neuroscience

Volumn 31, Issue 36, 2011, Pages 12823-12836

  Gu, Ming ^a   Miyoshi, Kan ^b   Dubner, Ronald ^a   Guo, Wei ^a   Zou, Shiping ^a   Ren, Ke ^a   Noguchi, Koichi ^b   Wei, Feng ^a  

^a UNIVERSITY OF MARYLAND DENTAL SCHOOL   (United States)

^b HYOGO UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINO 1 (6 CHLORO 2 PYRIDYL)PIPERIDINE; BRAIN DERIVED NEUROTROPHIC FACTOR; CD11B ANTIGEN; FRACTALKINE; GLIAL FIBRILLARY ACIDIC PROTEIN; INTERLEUKIN 18; INTERLEUKIN 18 RECEPTOR; INTERLEUKIN 1BETA; N METHYL DEXTRO ASPARTIC ACID RECEPTOR; SEROTONIN 3 RECEPTOR;

ALLODYNIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BEHAVIOR; CELL INTERACTION; CONTROLLED STUDY; FACILITATION; HYPERALGESIA; MALE; MEDULLA OBLONGATA; MICROGLIA; NERVE CELL EXCITABILITY; NERVE INJURY; NOCICEPTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RAT; ROSTRAL VENTROMEDIAL MEDULLA; SEROTONINERGIC SYSTEM; SIGNAL TRANSDUCTION; SPINAL CORD DORSAL HORN; UPREGULATION;

ANIMALS; BEHAVIOR, ANIMAL; BLOTTING, WESTERN; CHEMOKINES; CYTOKINES; ELECTRIC STIMULATION; EXCITATORY AMINO ACID AGONISTS; GENE TRANSFER TECHNIQUES; GLIAL FIBRILLARY ACIDIC PROTEIN; HYPERALGESIA; IMMUNOHISTOCHEMISTRY; INJECTIONS, SPINAL; INTERLEUKIN-18; INTERLEUKIN-1BETA; MALE; MICROINJECTIONS; NEUROGLIA; NEURONS; NEURONS, AFFERENT; NOCICEPTORS; PIPERIDINES; RATS; RATS, SPRAGUE-DAWLEY; RECEPTORS, CHEMOKINE; RECEPTORS, N-METHYL-D-ASPARTATE; RECEPTORS, SEROTONIN, 5-HT3; SEROTONIN RECEPTOR AGONISTS; SIGNAL TRANSDUCTION; SPINAL CORD;

EID: 80052589278     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1564-11.2011     Document Type: Article

References (68)

1. Aira Z, Buesa I, Salgueiro M, Bilbao J, Aguilera L, Zimmermann M, Azkue JJ (2010) Subtype-specific changes in 5-HT receptor-mediated modulation of C fibre-evoked spinal field potentials are triggered by peripheral nerve injury. Neuroscience 168:831-841.
2. Alhaider AA, Lei SZ, Wilcox GL (1991) Spinal 5-HT3 receptor-mediated antinociception: possible release of GABA. J Neurosci 11:1881-1888.
3. Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, Greaves DR, Zlotnik A, Schall TJ (1997) A new class of membrane-bound chemokine with a CX3C motif. Nature 385:640-644.
4. Burgess SE, Gardell LR, Ossipov MH, Malan TP Jr, Vanderah TW, Lai J, Porreca F (2002) Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain. J Neurosci 22:5129-5136.
5. Clark AK, Yip PK, Malcangio M (2009) The liberation of fractalkine in the dorsal horn requires microglial cathepsin S. J Neurosci 29:6945-6954.
6. Colburn RW, DeLeo JA, Rickman AJ, Yeager MP, Kwon P, Hickey WF (1997) Dissociation of microglial activation and neuropathic pain behaviors following peripheral nerve injury in the rat. J Neuroimmunol 79:163-175.
7. Conte D, Legg ED, McCourt AC, Silajdzic E, Nagy GG, Maxwell DJ (2005) Transmitter content, origins and connections of axons in the spinal cord that possess the serotonin (5-hydroxytryptamine) 3 receptor. Neuroscience 134:165-173.
8. DeLeo JA, Yezierski RP (2001) The role of neuroinflammation and neuroimmune activation in persistent pain. Pain 90:1-6.
9. Dogrul A, Ossipov MH, Porreca F (2009) Differential mediation of descending pain facilitation and inhibition by spinal 5HT-3 and 5HT-7 receptors. Brain Res 1280:52-59.
10. Fields HL, Heinricher MM, Mason P (1991) Neurotransmitters in nociceptive modulatory circuits. Annu Rev Neurosci 14:219-245.
11. Fukushima T, Ohtsubo T, Tsuda M, Yanagawa Y, Hori Y (2009) Facilitatory actions of serotonin type 3 receptors on GABAergic inhibitory synaptic transmission in the spinal superficial dorsal horn. J Neurophysiol 102:1459-1471.
12. Gao YJ, Ji RR (2010) Targeting astrocyte signaling for chronic pain. Neurotherapeutics 7:482-493.
13. Gebhart GF (2004) Descending modulation of pain. Neurosci Biobehav Rev 27:729-737.
14. Géranton SM, Fratto V, Tochiki KK, Hunt SP (2008) Descending serotonergic controls regulate inflammation-induced mechanical sensitivity and methyl-CpG-binding protein 2 phosphorylation in the rat superficial dorsal horn. Mol Pain 4:35.
15. Guo W, Zou S, Guan Y, Ikeda T, Tal M, Dubner R, Ren K (2002) Tyrosine phosphorylation of the NR2B subunit of theNMDAreceptor in the spinal cord during the development and maintenance of inflammatory hyperalgesia. J Neurosci 22:6208-6217.
16. Guo W, Robbins MT, Wei F, Zou S, Dubner R, Ren K (2006) Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for pain facilitation. J Neurosci 26:126-137.
17. Guo W, Wang H, Watanabe M, Shimizu K, Zou S, LaGraize SC, Wei F, Dubner R, Ren K (2007) Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J Neurosci 27:6006-6018.
18. Hammond DL, Yaksh TL (1984) Antagonism of stimulation-produced antinociception by intrathecal administration of methysergide or phentolamine. Brain Res 298:329-337.
19. Hammond DL, Tyce GM, Yaksh TL (1985) Efflux of 5-hydroxytryptamine and noradrenaline into spinal cord superfusates during stimulation of the rat medulla. J Physiol 359:151-162.
20. Hamon M, Bourgoin S (1999) Serotonin and its receptors in pain control. In: Novel aspects of pain management: opioids and beyond (Sawynok J, Cowan A, eds), pp 203-228. New York: Wiley.
21. Hansson E, Rönnbäck L (2004) Altered neuronal-glial signaling in glutamatergic transmission as a unifying mechanism in chronic pain and mental fatigue. Neurochem Res 29:989-996.
22. Huang J, Wang YY, Wang W, Li YQ, Tamamaki N, Wu SX (2008) 5-HT(3A) receptor subunit is expressed in a subpopulation of GABAergic and enkephalinergic neurons in the mouse dorsal spinal cord. Neurosci Lett 441:1-6.
23. Hylden JL, Wilcox GL (1980) Intrathecal morphine in mice: a new technique. Eur J Pharmacol 67:313-316.
24. Imai T, Hieshima K, Haskell C, Baba M, Nagira M, Nishimura M, Kakizaki M, Takagi S, Nomiyama H, Schall TJ, Yoshie O (1997) Identification and molecular characterization of fractalkine receptor CX3CR1, which mediates both leukocyte migration and adhesion. Cell 91:521-530.
25. Jeong CY, Choi JI, Yoon MH (2004) Roles of serotonin receptor subtypes for the antinociception of 5-HT in the spinal cord of rats. Eur J Pharmacol 502:205-211.
26. Kawasaki Y, Zhang L, Cheng JK, Ji RR (2008) Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 28:5189-5194.
27. Kia HK, Miquel MC, McKernan RM, Laporte AM, Lombard MC, Bourgoin S, Hamon M, Vergé D (1995) Localization of 5-HT3 receptors in the rat spinal cord: immunohistochemistry and in situ hybridization. Neuroreport 6:257-261.
28. Lagraize SC, Guo W, Yang K, Wei F, Ren K, Dubner R (2010) Spinal cord mechanisms mediating behavioral hyperalgesia induced by neurokinin-1 tachykinin receptor activation in the rostral ventromedial medulla. Neuroscience 171:1341-1356.
29. Lindia JA, McGowan E, Jochnowitz N, Abbadie C (2005) Induction of CX3CL1 expression in astrocytes and CX3CR1 in microglia in the spinal cord of a rat model of neuropathic pain. J Pain 6:434-438.
30. Lopez-Garcia JA (2006) Serotonergic modulation of spinal sensory circuits. Curr Top Med Chem 6:1987-1996.
31. Michael GJ, Averill S, Nitkunan A, Rattray M, Bennett DL, Yan Q, Priestley JV (1997) Nerve growth factor treatment increases brain-derived neurotrophic factor selectively in TrkA-expressing dorsal root ganglion cells and in their central terminations within the spinal cord. J Neurosci 17:8476-8490.
32. Millan MJ (2002) Descending control of pain. Prog Neurobiol 66:355-474.
33. Milligan ED, Watkins LR (2009) Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 10:23-36.
34. Milligan ED, Zapata V, Chacur M, Schoeniger D, Biedenkapp J, O'Connor KA, Verge GM, Chapman G, Green P, Foster AC, Naeve GS, Maier SF, Watkins LR (2004) Evidence that exogenous and endogenous fractalkine can induce spinal nociceptive facilitation in rats. Eur J Neurosci 20:2294-2302.
35. Milligan ED, Sloane EM, Watkins LR (2008) Glia in pathological pain: a role for fractalkine. J Neuroimmunol 198:113-120.
36. Miyoshi K, Obata K, Kondo T, Okamura H, Noguchi K (2008) Interleukin-18-mediated microglia/astrocyte interaction in the spinal cord enhances neuropathic pain processing after nerve injury. J Neurosci 28:12775-12787.
37. Morales M, Battenberg E, Bloom FE (1998) Distribution of neurons expressing immunoreactivity for the 5HT3 receptor subtype in the rat brain and spinal cord. J Comp Neurol 402:385-401.
38. Okazaki R, Namba H, Yoshida H, Okai H, Miura T, Kawamura M (2008) The antiallodynic effect of Neurotropin is mediated via activation of descending pain inhibitory systems in rats with spinal nerve ligation. Anesth Analg 107:1064-1069.
39. Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Amsterdam: Elsevier.
40. Pertovaara A (2000) Plasticity in descending pain modulatory systems. Prog Brain Res 129:231-242
41. Pertovaara A, Wei H, Hämäläinen MM (1996) Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats. Neurosci Lett 218:127-130.
42. Peters CM, Hayashida K, Ewan EE, Nakajima K, Obata H, Xu Q, Yaksh TL, Eisenach JC (2010) Lack of analgesic efficacy of spinal ondansetron on thermal and mechanical hypersensitivity following spinal nerve ligation in the rat. Brain Res 1352:83-93.
43. Porreca F, Ossipov MH, Gebhart GF (2002) Chronic pain and medullary descending facilitation. Trends Neurosci 25:319-325.
44. Raghavendra V, Tanga F, Rutkowski MD, DeLeo JA (2003) Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines. Pain 104:655-664.
45. Rahman W, Suzuki R, Webber M, Hunt SP, Dickenson AH (2006) Depletion of endogenous spinal 5-HT attenuates the behavioural hypersensitivity to mechanical and cooling stimuli induced by spinal nerve ligation. Pain 123:264-274.
46. Rahman W, Bauer CS, Bannister K, Vonsy JL, Dolphin AC, Dickenson AH (2009) Descending serotonergic facilitation and the antinociceptive effects of pregabalin in a rat model of osteoarthritic pain. Mol Pain 5:45.
47. Reeve AJ, Patel S, Fox A, Walker K, Urban L (2000) Intrathecally administered endotoxin or cytokines produce allodynia, hyperalgesia and changes in spinal cord neuronal responses to nociceptive stimuli in the rat. Eur J Pain 4:247-257.
48. Ren K, Dubner R (2007) Pain facilitation and activity-dependent plasticity in pain modulatory circuitry: role of BDNF-TrkB signaling and NMDA receptors. Mol Neurobiol 35:224-235.
49. Ren K, Dubner R (2008) Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol 21:570-579.
50. Ren K, Dubner R (2010) Interactions between the immune and nervous systems in pain. Nat Med 16:1267-1276.
51. Roberts MH (1984) 5-Hydroxytryptamine and antinociception. Neuropharmacology 23:1529-1536.
52. Sawynok J, Reid A (1996) Interactions of descending serotonergic systems with other neurotransmitters in the modulation of nociception. Behav Brain Res 73:63-68.
53. Scholz J, Woolf CJ (2007) The neuropathic pain triad: neurons, immune cells and glia. Nat Neurosci 10:1361-1368.
54. Staniland AA, Clark AK, Wodarski R, Sasso O, Maione F, D'Acquisto F, Malcangio M (2010) Reduced inflammatory and neuropathic pain and decreased spinal microglial response in fractalkine receptor (CX3CR1) knockout mice. J Neurochem 114:1143-1157.
55. Sung CS, Wen ZH, Chang WK, Chan KH, Ho ST, Tsai SK, Chang YC, Wong CS (2005) Inhibition of p38 mitogen-activated protein kinase attenuates interleukin-1beta-induced thermal hyperalgesia and inducible nitric oxide synthase expression in the spinal cord. J Neurochem 94:742-752.
56. Suzuki R, Morcuende S, Webber M, Hunt SP, Dickenson AH (2002) Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways. Nat Neurosci 5:1319-1326.
57. Tecott L.H, Maricq AV, Julius D (1993) Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proc Natl Acad Sci U S A 90:1430-1444.
58. Urban MO, Zahn PK, Gebhart GF (1999) Descending facilitatory influences from the rostral medial medulla mediate secondary, but not primary hyperalgesia in the rat. Neuroscience 90:349-352.
59. Verge GM, Milligan ED, Maier SF, Watkins LR, Naeve GS, Foster AC (2004) Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) distribution in spinal cord and dorsal root ganglia under basal and neuropathic pain conditions. Eur J Neurosci 20:1150-1160.
60. Wang H, Guo W, Yang K, Wei F, Dubner R, Ren K (2010) Contribution of primary afferent input to trigeminal astroglial hyperactivity, cytokine induction and NMDA receptor phosphorylation. Open Pain J 2010:144-152.
61. Watkins LR, Milligan ED, Maier SF (2001) Glial activation: a driving force for pathological pain. Trends Neurosci 24:450-455.
62. Wei F, Dubner R, Ren K (1999) Nucleus reticularis gigantocellularis and nucleus raphe magnus in the brain stem exert opposite effects on behavioral hyperalgesia and spinal Fos protein expression after peripheral inflammation. Pain 80:127-141.
63. Wei F, Guo W, Zou S, Ren K, Dubner R (2008) Supraspinal glial-neuronal interactions contribute to descending pain facilitation. J Neurosci 28:10482-10495.
64. Wei F, Dubner R, Zou S, Ren K, Bai G, Wei D, Guo W (2010) Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain. J Neurosci 30:8624-8636.
65. Yaksh TL, Wilson PR (1979) Spinal serotonin terminal system mediates antinociception. J Pharmacol Exp Ther 208:446-453.
66. Zeitz KP, Guy N, Malmberg AB, Dirajlal S, Martin WJ, Sun L, Bonhaus DW, Stucky CL, Julius D, Basbaum AI (2002) The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. J Neurosci 22:1010-1019.
67. Zhang RX, Liu B, Li A, Wang L, Ren K, Qiao JT, Berman BM, Lao L (2008) Interleukin 1beta facilitates bone cancer pain in rats by enhancing NMDA receptor NR-1 subunit phosphorylation. Neuroscience 154: 1533-1538.
68. Zhuo M, Gebhart GF (1991) Spinal serotonin receptors mediate descending facilitation of a nociceptive reflex from the nuclei reticularis gigantocellularis and gigantocellularis pars alpha in the rat. Brain Res 550:35-48.