Dorsal horn substance P and NK1 receptors: Study of a model system in spinal nociceptive processing

Synaptic Plasticity in Pain

Volumn , Issue , 2009, Pages 109-138

  Hua, Xiao Ying ^a   Yaksh, Tony L ^a  

^a University of California   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 74549196436     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4419-0226-9_6     Document Type: Chapter

References (205)

1. Abbadie, C., Lombard, M. C., Besson, J. M., Trafton, J. A. and Basbaum, A. I., 2002. Mu and delta opioid receptor-like immunoreactivity in the cervical spinal cord of the rat after dorsal rhizotomy or neonatal capsaicin: an analysis of pre- and postsynaptic receptor distributions. Brain Res. 930, 150-162.
2. Abbadie, C., Trafton, J., Liu, H., Mantyh, P. W. and Basbaum, A. I., 1997. Inflammation increases the distribution of dorsal horn neurons that internalize the neurokinin-1 receptor in response to noxious and non-noxious stimulation. J Neurosci. 17, 8049-8060.
3. Afrah, A. W., Stiller, C. O., Olgart, L., Brodin, E. and Gustafsson, H., 2001. Involvement of spinal N-methyl-D-aspartate receptors in capsaicin-induced in vivo release of substance P in the rat dorsal horn. Neurosci Lett. 316, 83-86.
4. Agarwal, N., Pacher, P., Tegeder, I., Amaya, F., Constantin, C. E., Brenner, G. J., Rubino, T., Michalski, C. W., Marsicano, G., Monory, K., Mackie, K., Marian, C., Batkai, S., Parolaro, D., Fischer, M. J., Reeh, P., Kunos, G., Kress, M., Lutz, B., Woolf, C. J. and Kuner, R., 2007. Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors. Nat Neurosci. 10, 870-879.
5. Ahluwalia, J., Urban, L., Bevan, S. and Nagy, I., 2003. Anandamide regulates neuropeptide release from capsaicin-sensitive primary sensory neurons by activating both the cannabinoid 1 receptor and the vanilloid receptor 1 in vitro. Eur J Neurosci. 17, 2611-2618.
6. Aimone, L. D. and Yaksh, T. L., 1989. Opioid modulation of capsaicin-evoked release of substance P from rat spinal cord in vivo. Peptides. 10, 1127-1131.
7. Akasu, T., Ishimatsu, M. and Yamada, K., 1996. Tachykinins cause inward current through NK1 receptors in bullfrog sensory neurons. Brain Res. 713, 160-167.
8. Allen, B. J., Rogers, S. D., Ghilardi, J. R., Menning, P. M., Kuskowski, M. A., Basbaum, A. I., Simone, D. A. and Mantyh, P. W., 1997. Noxious cutaneous thermal stimuli induce a graded release of endogenous substance P in the spinal cord: imaging peptide action in vivo. J Neurosci. 17, 5921-5927.
9. Allen, J. W., Mantyh, P. W., Horais, K., Tozier, N., Rogers, S. D., Ghilardi, J. R., Cizkova, D., Grafe, M. R., Richter, P., Lappi, D. A. and Yaksh, T. L., 2006. Safety evaluation of intrathecal substance P-saporin, a targeted neurotoxin, in dogs. Toxicol Sci. 91, 286-298.
10. Altier, C., Dale, C. S., Kisilevsky, A. E., Chapman, K., Castiglioni, A. J., Matthews, E. A., Evans, R. M., Dickenson, A. H., Lipscombe, D., Vergnolle, N. and Zamponi, G. W., 2007. Differential role of N-type calcium channel splice isoforms in pain. J Neurosci. 27, 6363-6373.
11. 2+ channels to treat pain: T-type versus N-type. Trends Pharmacol Sci. 25, 465-470.
12. Barber, L. A. and Vasko, M. R., 1996. Activation of protein kinase C augments peptide release from rat sensory neurons. J Neurochem. 67, 72-80.
13. Battaglia, G. and Rustioni, A., 1988. Coexistence of glutamate and substance P in dorsal root ganglion neurons of the rat and monkey. J Comp Neurol. 277, 302-312.
14. Bautista, D. M., Jordt, S. E., Nikai, T., Tsuruda, P. R., Read, A. J., Poblete, J., Yamoah, E. N., Basbaum, A. I. and Julius, D., 2006. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 124, 1269-1282.
15. Bell, T. J., Thaler, C., Castiglioni, A. J., Helton, T. D. and Lipscombe, D., 2004. Cell-specific alternative splicing increases calcium channel current density in the pain pathway. Neuron. 41, 127-138.
16. Bourgoin, S., Pohl, M., Mauborgne, A., Benoliel, J. J., Collin, E., Hamon, M. and Cesselin, F., 1993. Monoaminergic control of the release of calcitonin gene-related peptide- and substance P-like materials from rat spinal cord slices. Neuropharmacology. 32, 633-640.
17. Brimijoin, S., Lundberg, J. M., Brodin, E., Hokfelt, T. and Nilsson, G., 1980. Axonal transport of substance P in the vagus and sciatic nerves of the guinea pig. Brain Res. 191, 443-457.
18. Cahill, C. M. and Coderre, T. J., 2002. Attenuation of hyperalgesia in a rat model of neuropathic pain after intrathecal pre- or post-treatment with a neurokinin-1 antagonist. Pain. 95, 277-285.
19. Campbell, E. A., Gentry, C. T., Patel, S., Panesar, M. S., Walpole, C. S. and Urban, L., 1998. Selective neurokinin-1 receptor antagonists are anti-hyperalgesic in a model of neuropathic pain in the guinea-pig. Neuroscience. 87, 527-532.
20. Cao, Y. Q., Mantyh, P. W., Carlson, E. J., Gillespie, A. M., Epstein, C. J. and Basbaum, A. I., 1998. Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 392, 390-394.
21. Carbone, E., Giancippoli, A., Marcantoni, A., Guido, D. and Carabelli, V., 2006. A new role for T-type channels in fast "low-threshold" exocytosis. Cell Calcium. 40, 147-154.
22. Caron, M. G. and Lefkowitz, R. J., 1993. Catecholamine receptors: structure, function, and regulation. Recent Prog Horm Res. 48, 277-290.
23. Carter, M. S. and Krause, J. E., 1990. Structure, expression, and some regulatory mechanisms of the rat preprotachykinin gene encoding substance P, neurokinin A, neuropeptide K, and neuropeptide gamma. J Neurosci. 10, 2203-2214.
24. Castiglioni, A. J., Raingo, J. and Lipscombe, D., 2006. Alternative splicing in the C-terminus of CaV2.2 controls expression and gating of N-type calcium channels. J Physiol. 576, 119-134.
25. Caterina, M. J., Leffler, A., Malmberg, A. B., Martin, W. J., Trafton, J., Petersen-Zeitz, K. R., Koltzenburg, M., Basbaum, A. I. and Julius, D., 2000. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 288, 306-313.
26. Chang, H. M., Berde, C. B., Holz, G. G. t., Steward, G. F. and Kream, R. M., 1989. Sufentanil, morphine, met-enkephalin, and kappa-agonist (U-50, 488H) inhibit substance P release from primary sensory neurons: a model for presynaptic spinal opioid actions. Anesthesiology. 70, 672-677.
27. Chang, M. M., Leeman, S. E. and Niall, H. D., 1971. Amino-acid sequence of substance P. Nat New Biol. 232, 86-87.
28. Chapman, V. and Dickenson, A. H., 1993. The effect of intrathecal administration of RP67580, a potent neurokinin 1 antagonist on nociceptive transmission in the rat spinal cord. Neurosci Lett. 157, 149-152.
29. Cheng, P. Y., Moriwaki, A., Wang, J. B., Uhl, G. R. and Pickel, V. M., 1996. Ultrastructural localization of mu-opioid receptors in the superficial layers of the rat cervical spinal cord: extrasynaptic localization and proximity to Leu5-enkephalin. Brain Res. 731, 141-154.
30. Cui, M., Honore, P., Zhong, C., Gauvin, D., Mikusa, J., Hernandez, G., Chandran, P., Gomtsyan, A., Brown, B., Bayburt, E. K., Marsh, K., Bianchi, B., McDonald, H., Niforatos, W., Neelands, T. R., Moreland, R. B., Decker, M. W., Lee, C. H., Sullivan, J. P. and Faltynek, C. R., 2006. TRPV1 receptors in the CNS play a key role in broadspectrum analgesia of TRPV1 antagonists. J Neurosci. 26, 9385-9393.
31. De Biasi, S. and Rustioni, A., 1988. Glutamate and substance P coexist in primary afferent terminals in the superficial laminae of spinal cord. Proceedings of the National Academy of Science USA. 85, 7820-7824.
32. De Felipe, C., Herrero, J. F., O'Brien, J. A., Palmer, J. A., Doyle, C. A., Smith, A. J., Laird, J. M., Belmonte, C., Cervero, F. and Hunt, S. P., 1998. Altered nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature. 392, 394-397.
33. 2+ promotes calcitonin gene-related peptide release from central terminals of capsaicin-sensitive afferents of guinea pigs: effect of capsaicin, high K+ and low pH media. Brain Res. 566, 46-53.
34. Dememes, D., Seoane, A., Venteo, S. and Desmadryl, G., 2000. Efferent function of vestibular afferent endings? Similar localization of N-type calcium channels, synaptic vesicle and synaptic membrane-associated proteins. Neuroscience. 98, 377-384.
35. Dionne, R. A., Max, M. B., Gordon, S. M., Parada, S., Sang, C., Gracely, R. H., Sethna, N. F. and MacLean, D. B., 1998. The substance P receptor antagonist CP-99, 994 reduces acute postoperative pain. Clin Pharmacol Ther. 64, 562-568.
36. Dolphin, A. C. and Scott, R. H., 1987. Calcium channel currents and their inhibition by (-)-baclofen in rat sensory neurones: modulation by guanine nucleotides. J Physiol. 386, 1-17.
37. Duggan, A. W., Hendry, I. A., Morton, C. R., Hutchison, W. D. and Zhao, Z. Q., 1988. Cutaneous stimuli releasing immunoreactive substance P in the dorsal horn of the cat. Brain Res. 451, 261-273.
38. Duggan, A. W., Hope, P. J., Jarrott, B., Schaible, H. G. and Fleetwood-Walker, S. M., 1990. Release, spread and persistence of immunoreactive neurokinin A in the dorsal horn of the cat following noxious cutaneous stimulation. Studies with antibody microprobes. Neuroscience. 35, 195-202.
39. Duggan, A. W., Hope, P. J. and Lang, C. W., 1991. Microinjection of neuropeptide Y into the superficial dorsal horn reduces stimulus-evoked release of immunoreactive substance P in the anaesthetized cat. Neuroscience. 44, 733-740.
40. Evans, A. R., Nicol, G. D. and Vasko, M. R., 1996. Differential regulation of evoked peptide release by voltage-sensitive calcium channels in rat sensory neurons. Brain Res. 712, 265-273.
41. Fehrenbacher, J. C., Taylor, C. P. and Vasko, M. R., 2003. Pregabalin and gabapentin reduce release of substance P and CGRP from rat spinal tissues only after inflammation or activation of protein kinase C. Pain. 105, 133-141.
42. Field, M. J., Cox, P. J., Stott, E., Melrose, H., Offord, J., Su, T. Z., Bramwell, S., Corradini, L., England, S., Winks, J., Kinloch, R. A., Hendrich, J., Dolphin, A. C., Webb, T. and Williams, D., 2006. Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci USA. 103, 17537-17542.
43. Fields, H. L., Emson, P. C., Leigh, B. K., Gilbert, R. F. and Iversen, L. L., 1980. Multiple opiate receptor sites on primary afferent fibres. Nature. 284, 351-353.
44. Fyffe, R. E. and Perl, E. R., 1984. Is ATP a central synaptic mediator for certain primary afferent fibers from mammalian skin? Proc Natl Acad Sci USA. 81, 6890-6893.
45. Gamse, R., Molnar, A. and Lembeck, F., 1979. Substance P release from spinal cord slices by capsaicin. Life Sci. 25, 629-636.
46. Ghilardi, J. R., Svensson, C. I., Rogers, S. D., Yaksh, T. L. and Mantyh, P. W., 2004. Constitutive spinal cyclooxygenase-2 participates in the initiation of tissue injury-induced hyperalgesia. J Neurosci. 24, 2727-2732.
47. Gibson, S. J., Polak, J. M., Bloom, S. R., Sabate, I. M., Mulderry, P. M., Ghatei, M. A., McGregor, G. P., Morrison, J. F., Kelly, J. S., Evans, R. M. and et al., 1984. Calcitonin gene-related peptide immunoreactivity in the spinal cord of man and of eight other species. J Neurosci. 4, 3101-3111.
48. Go, V. L. and Yaksh, T. L., 1987. Release of substance P from the cat spinal cord. J Physiol. 391, 141-167.
49. Grudt, T. J. and Williams, J. T., 1994. mu-Opioid agonists inhibit spinal trigeminal substantia gelatinosa neurons in guinea pig and rat. J Neurosci. 14, 1646-1654.
50. Gu, G., Kondo, I., Hua, X. Y. and Yaksh, T. L., 2005. Resting and evoked spinal substance P release during chronic intrathecal morphine infusion: parallels with tolerance and dependence. J Pharmacol Exp Ther. 314, 1362-1369.
51. Guan, J. S., Xu, Z. Z., Gao, H., He, S. Q., Ma, G. Q., Sun, T., Wang, L. H., Zhang, Z. N., Lena, I., Kitchen, I., Elde, R., Zimmer, A., He, C., Pei, G., Bao, L. and Zhang, X., 2005. Interaction with vesicle luminal protachykinin regulates surface expression of delta-opioid receptors and opioid analgesia. Cell. 122, 619-631.
52. 2+ channels to nociceptive transmission in rat spinal lamina I neurons. Eur J Neurosci. 19, 103-111.
53. Hill, R., 2000. NK1 (substance P) receptor antagonists - why are they not analgesic in humans? Trends Pharmacol Sci. 21, 244-246.
54. Hingtgen, C. M. and Vasko, M. R., 1994. Prostacyclin enhances the evoked-release of substance P and calcitonin gene-related peptide from rat sensory neurons. Brain Res. 655, 51-60.
55. Hokfelt, T., Arvidsson, U., Cullheim, S., Millhorn, D., Nicholas, A. P., Pieribone, V., Seroogy, K. and Ulfhake, B., 2000. Multiple messengers in descending serotonin neurons: localization and functional implications. J Chem Neuroanat. 18, 75-86.
56. Hokfelt, T., Kellerth, J. O., Nilsson, G. and Pernow, B., 1975. Substance P localization in the central nervous system and in some primary sensory neurons. Science. 190, 889-890.
57. Hokfelt, T., Pernow, B. and Wahren, J., 2001. Substance P: a pioneer amongst neuropeptides. J Intern Med. 249, 27-40.
58. Holmgren, S. and Jensen, J., 2001. Evolution of vertebrate neuropeptides. Brain Res Bull. 55, 723-735.
59. Holzer, P., 1991. Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev. 43, 143-201.
60. Honor, P., Menning, P. M., Rogers, S. D., Nichols, M. L., Basbaum, A. I., Besson, J. M. and Mantyh, P. W., 1999. Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states. J Neurosci. 19, 7670-7678.
61. Honore, P., Menning, P. M., Rogers, S. D., Nichols, M. L. and Mantyh, P. W., 2000. Neurochemical plasticity in persistent inflammatory pain. Prog Brain Res. 129, 357-363.
62. Hua, F., Ricketts, B. A., Reifsteck, A., Ardell, J. L. and Williams, C. A., 2004. Myocardial ischemia induces the release of substance P from cardiac afferent neurons in rat thoracic spinal cord. Am J Physiol Heart Circ Physiol. 286, H1654-1664.
63. Hua, X. Y., Boublik, J. H., Spicer, M. A., Rivier, J. E., Brown, M. R. and Yaksh, T. L., 1991. The antinociceptive effects of spinally administered neuropeptide Y in the rat: systematic studies on structure-activity relationship. J Pharmacol Exp Ther. 258, 243-248.
64. Hua, X. Y., Chen, P., Marsala, M. and Yaksh, T. L., 1999. Intrathecal substance P-induced thermal hyperalgesia and spinal release of prostaglandin E2 and amino acids. Neuroscience. 89, 525-534.
65. Hua, X. Y., Chen, P., Polgar, E., Nagy, I., Marsala, M., Phillips, E., Wollaston, L., Urban, L., Yaksh, T. L. and Webb, M., 1998. Spinal neurokinin NK1 receptor down-regulation and antinociception: effects of spinal NK1 receptor antisense oligonucleotides and NK1 receptor occupancy. J Neurochem. 70, 688-698.
66. Hua, X. Y., Theodorsson-Norheim, E., Brodin, E., Lundberg, J. M. and Hokfelt, T., 1985. Multiple tachykinins (Neurokinin A, Neuropeptide K and Substance P) in capsaicinsensitive sensory neurons in the guinea-pig. Regul Pept. 13, 1-19.
67. Huang, H., Wu, X., Nicol, G. D., Meller, S. and Vasko, M. R., 2003. ATP augments peptide release from rat sensory neurons in culture through activation of P2Y receptors. J Pharmacol Exp Ther. 306, 1137-1144.
68. Hunt, S. P. and Mantyh, P. W., 2001. The molecular dynamics of pain control. Nat Rev Neurosci. 2, 83-91.
69. Ikeda, H., Heinke, B., Ruscheweyh, R. and Sandkühler, J., 2003. Synaptic plasticity in spinal lamina I projection neurons that mediate hyperalgesia. Science. 299, 1237-1240.
70. Inoue, A., Hashimoto, T., Hide, I., Nishio, H. and Nakata, Y., 1997. 5-Hydroxytryptaminefacilitated release of substance P from rat spinal cord slices is mediated by nitric oxide and cyclic GMP. J Neurochem. 68, 128-133.
71. Ito, K., Rome, C., Bouleau, Y. and Dulon, D., 2002. Substance P mobilizes intracellular calcium and activates a nonselective cation conductance in rat spiral ganglion neurons. Eur J Neurosci. 16, 2095-2102.
72. Iyengar, S., Hipskind, P. A., Gehlert, D. R., Schober, D., Lobb, K. L., Nixon, J. A., Helton, D. R., Kallman, M. J., Boucher, S., Couture, R., Li, D. L. and Simmons, R. M., 1997. LY303870, a centrally active neurokinin-1 antagonist with a long duration of action. J Pharmacol Exp Ther. 280, 774-785.
73. Jessell, T. M. and Iversen, L. L., 1977. Opiate analgesics inhibit substance P release from rat trigeminal nucleus. Nature. 268, 549-551.
74. Jhamandas, K., Yaksh, T. L., Harty, G., Szolcsanyi, J. and Go, V. L., 1984. Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: selectivity of action and relationship to analgesia. Brain Res. 306, 215-225.
75. Jo, Y. H. and Schlichter, R., 1999. Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci. 2, 241-245.
76. Kangawa, K., Minamino, N., Fukuda, A. and Matsuo, H., 1983. Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Commun. 114, 533-540.
77. Khasabov, S. G., Rogers, S. D., Ghilardi, J. R., Peters, C. M., Mantyh, P. W. and Simone, D. A., 2002. Spinal neurons that possess the substance P receptor are required for the development of central sensitization. J Neurosci. 22, 9086-9098.
78. Khasabova, I. A., Harding-Rose, C., Simone, D. A. and Seybold, V. S., 2004. Differential effects of CB1 and opioid agonists on two populations of adult rat dorsal root ganglion neurons. J Neurosci. 24, 1744-1753.
79. Kjorsvik Bertelsen, A., Warsame Afrah, A., Gustafsson, H., Tjolsen, A., Hole, K. and Stiller, C. O., 2003. Stimulation of spinal 5-HT (2A/2C) receptors potentiates the capsaicininduced in vivo release of substance P-like immunoreactivity in the rat dorsal horn. Brain Res. 987, 10-16.
80. Kondo, I., Marvizon, J. C., Song, B., Salgado, F., Codeluppi, S., Hua, X. Y. and Yaksh, T. L., 2005. Inhibition by spinal mu- and delta-opioid agonists of afferent-evoked substance P release. J Neurosci. 25, 3651-3660.
81. Kotani, H., Hoshimaru, M., Nawa, H. and Nakanishi, S., 1986. Structure and gene organization of bovine neuromedin K precursor. Proc Natl Acad Sci USA. 83, 7074-7078.
82. Krause, J. E., Chirgwin, J. M., Carter, M. S., Xu, Z. S. and Hershey, A. D., 1987. Three rat preprotachykinin mRNAs encode the neuropeptides substance P and neurokinin A. Proc Natl Acad Sci USA. 84, 881-885.
83. Kumazawa, T., Mizumura, K., Koda, H. and Fukusako, H., 1996. EP receptor subtypes implicated in the PGE2-induced sensitization of polymodal receptors in response to bradykinin and heat. J Neurophysiol. 75, 2361-2368.
84. Kuraishi, Y., Hirota, N., Sato, Y., Hanashima, N., Takagi, H. and Satoh, M., 1989. Stimulus specificity of peripherally evoked substance P release from the rabbit dorsal horn in situ. Neuroscience. 30, 241-250.
85. Lao, L. and Marvizon, J. C., 2005. GABA (A) receptor facilitation of neurokinin release from primary afferent terminals in the rat spinal cord. Neuroscience. 130, 1013-1027.
86. Lembeck, F., 1953. Zur Frage der zentralen Ubertragung afferenter Impulse III. Mitteilung. Das Vorommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Ruckenmarks. Naunyn Schmiedebergs Arch Pharmacol. 219, 197-213.
87. Linderoth, B. and Brodin, E., 1988. Tachykinin release from rat spinal cord in vitro and in vivo in response to various stimuli. Regul Pept. 21, 129-140.
88. Liu, H., Brown, J. L., Jasmin, L., Maggio, J. E., Vigna, S. R., Mantyh, P. W. and Basbaum, A. I., 1994a. Synaptic relationship between substance P and the substance P receptor: light and electron microscopic characterization of the mismatch between neuropeptides and their receptors. Proc Natl Acad Sci USA. 91, 1009-1013.
89. Liu, H., Mantyh, P. W. and Basbaum, A. I., 1997. NMDA-receptor regulation of substance P release from primary afferent nociceptors. Nature. 386, 721-724.
90. Liu, H., Wang, H., Sheng, M., Jan, L. Y., Jan, Y. N. and Basbaum, A. I., 1994b. Evidence for presynaptic N-methyl-D-aspartate autoreceptors in the spinal cord dorsal horn. Proc Natl Acad Sci USA. 91, 8383-8387.
91. Liu, X. and Sandkühler, J., 1997. Characterization of long-term potentiation of C-fiberevoked potentials in spinal dorsal horn of adult rat: essential role of NK1 and NK2 receptors. J Neurophysiol. 78, 1973-1982.
92. Maggi, C. A., 1995. The mammalian tachykinin receptors. Gen Pharmacol. 26, 911-944.
93. Malcangio, M. and Bowery, N. G., 1993. Gamma-aminobutyric acidB, but not gammaaminobutyric acidA receptor activation, inhibits electrically evoked substance P-like immunoreactivity release from the rat spinal cord in vitro. J Pharmacol Exp Ther. 266, 1490-1496.
94. Malcangio, M. and Bowery, N. G., 1996. GABA and its receptors in the spinal cord. Trends Pharmacol Sci. 17, 457-462.
95. Malcangio, M. and Bowery, N. G., 1999. Peptide autoreceptors: does an autoreceptor for substance P exist? Trends Pharmacol Sci. 20, 405-407.
96. Malcangio, M., Fernandes, K. and Tomlinson, D. R., 1998. NMDA receptor activation modulates evoked release of substance P from rat spinal cord. Br J Pharmacol. 125, 1625-1626.
97. Malcangio, M., Garrett, N. E., Cruwys, S. and Tomlinson, D. R., 1997. Nerve growth factorand neurotrophin-3-induced changes in nociceptive threshold and the release of substance P from the rat isolated spinal cord. J Neurosci. 17, 8459-8467.
98. Malcangio, M., Ramer, M. S., Boucher, T. J. and McMahon, S. B., 2000. Intrathecally injected neurotrophins and the release of substance P from the rat isolated spinal cord. Eur J Neurosci. 12, 139-144.
99. Malmberg, A. B. and Yaksh, T. L., 1992. Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science. 257, 1276-1279.
100. Mantyh, P. W., Allen, C. J., Ghilardi, J. R., Rogers, S. D., Mantyh, C. R., Liu, H., Basbaum, A. I., Vigna, S. R. and Maggio, J. E., 1995a. Rapid endocytosis of a G protein-coupled receptor: substance P evoked internalization of its receptor in the rat striatum in vivo. Proc Natl Acad Sci USA. 92, 2622-2626.
101. Mantyh, P. W., DeMaster, E., Malhotra, A., Ghilardi, J. R., Rogers, S. D., Mantyh, C. R., Liu, H., Basbaum, A. I., Vigna, S. R., Maggio, J. E. and et al., 1995b. Receptor endocytosis and dendrite reshaping in spinal neurons after somatosensory stimulation. Science. 268, 1629-1632.
102. Mantyh, P. W., Rogers, S. D., Honore, P., Allen, B. J., Ghilardi, J. R., Li, J., Daughters, R. S., Lappi, D. A., Wiley, R. G. and Simone, D. A., 1997. Inhibition of hyperalgesia by ablation of lamina I spinal neurons expressing the substance P receptor. Science. 278, 275-279.
103. Martin, H. A., Basbaum, A. I., Kwiat, G. C., Goetzl, E. J. and Levine, J. D., 1987. Leukotriene and prostaglandin sensitization of cutaneous high-threshold C- and A-delta mechanonociceptors in the hairy skin of rat hindlimbs. Neuroscience. 22, 651-659.
104. Marvizon, J. C., Grady, E. F., Stefani, E., Bunnett, N. W. and Mayer, E. A., 1999. Substance P release in the dorsal horn assessed by receptor internalization: NMDA receptors counteract a tonic inhibition by GABA (B) receptors. Eur J Neurosci. 11, 417-426.
105. Marvizon, J. C., Martinez, V., Grady, E. F., Bunnett, N. W. and Mayer, E. A., 1997. Neurokinin 1 receptor internalization in spinal cord slices induced by dorsal root stimulation is mediated by NMDA receptors. J Neurosci. 17, 8129-8136.
106. Marvizon, J. C., Wang, X., Matsuka, Y., Neubert, J. K. and Spigelman, I., 2003. Relationship between capsaicin-evoked substance P release and neurokinin 1 receptor internalization in the rat spinal cord. Neuroscience. 118, 535-545.
107. Mauborgne, A., Bourgoin, S., Benoliel, J. J., Hirsch, M., Berthier, J. L., Hamon, M. and Cesselin, F., 1987. Enkephalinase is involved in the degradation of endogenous substance P released from slices of rat substantia nigra. J Pharmacol Exp Ther. 243, 674-680.
108. McCarson, K. E. and Krause, J. E., 1994. NK-1 and NK-3 type tachykinin receptor mRNA expression in the rat spinal cord dorsal horn is increased during adjuvant or formalininduced nociception. J Neurosci. 14, 712-720.
109. McCarthy, P. W. and Lawson, S. N., 1989. Cell type and conduction velocity of rat primary sensory neurons with substance P-like immunoreactivity. Neuroscience. 28, 745-753.
110. McLeod, A. L., Krause, J. E. and Ribeiro-Da-Silva, A., 2000. Immunocytochemical localization of neurokinin B in the rat spinal dorsal horn and its association with substance P and GABA: an electron microscopic study. J Comp Neurol. 420, 349-362.
111. McMahon, S. B., Cafferty, W. B. and Marchand, F., 2005. Immune and glial cell factors as pain mediators and modulators. Exp Neurol. 192, 444-462.
112. Menon-Johansson, A. S., Berrow, N. and Dolphin, A. C., 1993. G (o) transduces GABAB-receptor modulation of N-type calcium channels in cultured dorsal root ganglion neurons. Pflugers Arch. 425, 335-343.
113. Merighi, A., Polak, J. M. and Theodosis, D. T., 1991. 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.
114. Michael, G. J., Averill, S., Nitkunan, A., Rattray, M., Bennett, D. L., Yan, Q. and Priestley, J. V., 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.
115. Naim, M., Spike, R. C., Watt, C., Shehab, S. A. and Todd, A. J., 1997. Cells inlaminae III and IV of the rat spinal cord that possess the neurokinin-1 receptor and have dorsally directed dendrites receive a major synaptic input from tachykinin-containing primary afferents. J Neurosci. 17, 5536-5548.
116. Nakatsuka, T. and Gu, J. G., 2001. ATP P2X receptor-mediated enhancement of glutamate release and evoked EPSCs in dorsal horn neurons of the rat spinal cord. J Neurosci. 21, 6522-6531.
117. Nakatsuka, T., Mena, N., Ling, J. and Gu, J. G., 2001. Depletion of substance P from rat primary sensory neurons by ATP, an implication of P2X receptor-mediated release of substance P. Neuroscience. 107, 293-300.
118. Naveilhan, P., Hassani, H., Lucas, G., Blakeman, K. H., Hao, J. X., Xu, X. J., Wiesenfeld-Hallin, Z., Thoren, P. and Ernfors, P., 2001. Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor. Nature. 409, 513-517.
119. Nawa, H., Hirose, T., Takashima, H., Inayama, S. and Nakanishi, S., 1983. Nucleotide sequences of cloned cDNAs for two types of bovine brain substance P precursor. Nature. 306, 32-36.
120. Nazarian A., Christianson, C. A., Hua, X.-Y. and Yaksh, T. L., 2008a. Dexmedetomidine and ST91 anlgesia in the formalin model is mediated by alpha 2A adrenoceptors: a mechanism of action distinct from morphine. Neuroscience. 152, 119-127.
121. Nazarian, A., Gu, G., Gracias, N. G., Wilkinson, K., Hua, X. Y., Vasko, M. R. and Yaksh, T. L., 2008b. Spinal N-methyl-D-aspartate receptors and nociception-evoked release of primary afferent substance P. Neuroscience. 152, 119-127.
122. Neugebauer, V., Schaible, H. G., Weiretter, F. and Freudenberger, U., 1994. The involvement of substance P and neurokinin-1 receptors in the responses of rat dorsal horn neurons to noxious but not to innocuous mechanical stimuli applied to the knee joint. Brain Res. 666, 207-215.
123. Nicholas, A. P., Pieribone, V. A. and Hokfelt, T., 1993. Cellular localization of messenger RNA for beta-1 and beta-2 adrenergic receptors in rat brain: an in situ hybridization study. Neuroscience. 56, 1023-1039.
124. Nichols, M. L., Allen, B. J., Rogers, S. D., Ghilardi, J. R., Honore, P., Luger, N. M., Finke, M. P., Li, J., Lappi, D. A., Simone, D. A. and Mantyh, P. W., 1999. Transmission of chronic nociception by spinal neurons expressing the substance P receptor. Science. 286, 1558-1561.
125. Nicol, G. D., Klingberg, D. K. and Vasko, M. R., 1992. Prostaglandin E2 increases calcium conductance and stimulates release of substance P in avian sensory neurons. J Neurosci. 12, 1917-1927.
126. Ohkubo, H. and Nakanishi, S., 1991. Molecular characterization of the three tachykinin receptors. Ann NY Acad Sci. 632, 53-62.
127. Ono, H., Mishima, A., Ono, S., Fukuda, H. and Vasko, M. R., 1991. Inhibitory effects of clonidine and tizanidine on release of substance P from slices of rat spinal cord and antagonism by alpha-adrenergic receptor antagonists. Neuropharmacology. 30, 585-589.
128. Okano, K., Kuraishi, Y. and Satoh, M., 1998. Involvement of spinal substance P and excitatory amino acids in inflammatory hyperalgesia in rats. Jpn J Pharmacol. 76, 15-22.
129. Otsuka, M. and Konishi, S., 1976. release of substance P-like immunoreactivity from isolated spinal cord of newborn rat. Nature. 264, 83-84.
130. Otsuka, M. and Yoshioka, K., 1993. Neurotransmitter functions of mammalian tachykinins. Physiol Rev. 73, 229-308.
131. Pang, I. H. and Vasko, M. R., 1986. Morphine and norepinephrine but not 5-hydroxytryptamine and gamma-aminobutyric acid inhibit the potassium-stimulated release of substance P from rat spinal cord slices. Brain Res. 376, 268-279.
132. Pennefather, J. N., Lecci, A., Candenas, M. L., Patak, E., Pinto, F. M. and Maggi, C. A., 2004. Tachykinins and tachykinin receptors: a growing family. Life Sci. 74, 1445-1463.
133. Pernow, B., 1953. Studies on substance P purification, occurrence, and biological actions. Acta Physiol Scand. 29, 1-90.
134. Pernow, B., 1983. Substance P. Pharmacol Rev. 35, 85-141.
135. Petruska, J. C., Cooper, B. Y., Gu, J. G., Rau, K. K. and Johnson, R. D., 2000. Distribution of P2X1, P2X2, and P2X3 receptor subunits in rat primary afferents: relation to population markers and specific cell types. J Chem Neuroanat. 20, 141-162.
136. Pezet, S., Onteniente, B., Jullien, J., Junier, M. P., Grannec, G., Rudkin, B. B. and Calvino, B., 2001. Differential regulation of NGF receptors in primary sensory neurons by adjuvantinduced arthritis in the rat. Pain. 90, 113-125.
137. Pohl, M., Mauborgne, A., Bourgoin, S., Benoliel, J. J., Hamon, M. and Cesselin, F., 1989. Neonatal capsaicin treatment abolishes the modulations by opioids of substance P release from rat spinal cord slices. Neurosci Lett. 96, 102-107.
138. Polgar, E., Furuta, T., Kaneko, T. and Todd, A., 2006. Characterization of neurons that express preprotachykinin B in the dorsal horn of the rat spinal cord. Neuroscience. 139, 687-697.
139. Price, G. W., Wilkin, G. P., Turnbull, M. J. and Bowery, N. G., 1984. Are baclofen-sensitive GABAB receptors present on primary afferent terminals of the spinal cord? Nature. 307, 71-74.
140. Raingo, J., Castiglioni, A. J. and Lipscombe, D., 2007. Alternative splicing controls G protein-dependent inhibition of N-type calcium channels in nociceptors. Nat Neurosci. 10, 285-292.
141. Ralevic, V. and Burnstock, G., 1998. Receptors for purines and pyrimidines. Pharmacol Rev. 50, 413-492.
142. Regoli, D., Nguyen, Q. T. and Jukic, D., 1994. Neurokinin receptor subtypes characterized by biological assays. Life Sci. 54, 2035-2047.
143. Ribeiro-da-Silva, A. and Hokfelt, T., 2000. Neuroanatomical localisation of Substance P in the CNS and sensory neurons. Neuropeptides. 34, 256-271.
144. Riley, R. C., Trafton, J. A., Chi, S. I. and Basbaum, A. I., 2001. Presynaptic regulation of spinal cord tachykinin signaling via GABA (B) but not GABA (A) receptor activation. Neuroscience. 103, 725-737.
145. Ryu, P. D. and Randic, M., 1990. Low- and high-voltage-activated calcium currents in rat spinal dorsal horn neurons. J Neurophysiol. 63, 273-285.
146. Salter, M. W., De Koninck, Y. and Henry, J. L., 1993. Physiological roles for adenosine and ATP in synaptic transmission in the spinal dorsal horn. Prog Neurobiol. 41, 125-156.
147. Samad, T. A., Moore, K. A., Sapirstein, A., Billet, S., Allchorne, A., Poole, S., Bonventre, J. V. and Woolf, C. J., 2001. Interleukin-1beta-mediated induction of Cox-2 in the CNS contributes to inflammatory pain hypersensitivity. Nature. 410, 471-475.
148. Saria, A., Javorsky, F., Humpel, C. and Gamse, R., 1990. 5-HT3 receptor antagonists inhibit sensory neuropeptide release from the rat spinal cord. Neuroreport. 1, 104-106.
149. Sawynok, J., Downie, J. W., Reid, A. R., Cahill, C. M. and White, T. D., 1993. ATP release from dorsal spinal cord synaptosomes: characterization and neuronal origin. Brain Res. 610, 32-38.
150. Sawynok, J. and Liu, X. J., 2003. Adenosine in the spinal cord and periphery: release and regulation of pain. Prog Neurobiol. 69, 313-340.
151. Schmidlin, F., Roosterman, D. and Bunnett, N. W., 2003. The third intracellular loop and carboxyl tail of neurokinin 1 and 3 receptors determine interactions with beta-arrestins. Am J Physiol Cell Physiol. 285, C945-958.
152. 2+ currents, but spares a sustained current. Neuron. 6, 13-20.
153. Severini, C., Improta, G., Falconieri-Erspamer, G., Salvadori, S. and Erspamer, V., 2002. The tachykinin peptide family. Pharmacol Rev. 54, 285-322.
154. Seybold, V. S., Grkovic, I., Portbury, A. L., Ding, Y. Q., Shigemoto, R., Mizuno, N., Furness, J. B. and Southwell, B. R., 1997. Relationship of NK3 receptor-immunoreactivity to subpopulations of neurons in rat spinal cord. J Comp Neurol. 381, 439-448.
155. Shigemoto, R., Ohishi, H., Nakanishi, S. and Mizuno, N., 1992. Expression of the mRNA for the rat NMDA receptor (NMDAR1) in the sensory and autonomic ganglion neurons. Neurosci Lett. 144, 229-232.
156. Skofitsch, G. and Jacobowitz, D. M., 1985. Calcitonin gene-related peptide coexists with substance P in capsaicin sensitive neurons and sensory ganglia of the rat. Peptides. 6, 747-754.
157. Smart, D. and Jerman, J. C., 2000. Anandamide: an endogenous activator of the vanilloid receptor. Trends Pharmacol Sci. 21, 134.
158. Smith, J. A., Davis, C. L. and Burgess, G. M., 2000. Prostaglandin E2-induced sensitization of bradykinin-evoked responses in rat dorsal root ganglion neurons is mediated by cAMP-dependent protein kinase A. Eur J Neurosci. 12, 3250-3258.
159. Smith, M. T., Cabot, P. J., Ross, F. B., Robertson, A. D. and Lewis, R. J., 2002. The novel N-type calcium channel blocker, AM336, produces potent dose-dependent antinociception after intrathecal dosing in rats and inhibits substance P release in rat spinal cord slices. Pain. 96, 119-127.
160. 2+ channel currents in magnocellular neurones of the rat supraoptic nucleus. J Physiol. 513(Pt 3), 787-804.
161. Southall, M. D., Michael, R. L. and Vasko, M. R., 1998. Intrathecal NSAIDS attenuate inflammation-induced neuropeptide release from rat spinal cord slices. Pain. 78, 39-48.
162. Southall, M. D. and Vasko, M. R., 2001. Prostaglandin receptor subtypes, EP3C and EP4, mediate the prostaglandin E2-induced cAMP production and sensitization of sensory neurons. J Biol Chem. 276, 16083-16091.
163. 2C adrenergic receptor immunoreactivity in the rat spinal cord. J Neurosci. 18, 5928-5937.
164. Sutton, K. G., Martin, D. J., Pinnock, R. D., Lee, K. and Scott, R. H., 2002. Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 135, 257-265.
165. Suzuki, R., Morcuende, S., Webber, M., Hunt, S. P. and Dickenson, A. H., 2002. Superficial NK1-expressing neurons control spinal excitability through activation of descending pathways. Nat Neurosci. 5, 1319-1326.
166. Suzuki, R., Rahman, W., Rygh, L. J., Webber, M., Hunt, S. P. and Dickenson, A. H., 2005. Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. Pain. 117, 292-303.
167. Svensson, C. I., Fitzsimmons, B., Azizi, S., Powell, H. C., Hua, X. Y. and Yaksh, T. L., 2005. Spinal p38beta isoform mediates tissue injury-induced hyperalgesia and spinal sensitization. J Neurochem. 92, 1508-1520.
168. Svensson, C. I., Marsala, M., Westerlund, A., Calcutt, N. A., Campana, W. M., Freshwater, J. D., Catalano, R., Feng, Y., Protter, A. A., Scott, B. and Yaksh, T. L., 2003. Activation of p38 mitogen-activated protein kinase in spinal microglia is a critical link in inflammationinduced spinal pain processing. J Neurochem. 86, 1534-1544.
169. Svensson, C. I. and Yaksh, T. L., 2002. The spinal phospholipase-cyclooxygenase-prostanoid cascade in nociceptive processing. Annu Rev Pharmacol Toxicol. 42, 553-583.
170. Takano, M., Takano, Y. and Yaksh, T. L., 1993. Release of calcitonin gene-related peptide (CGRP), substance P (SP), and vasoactive intestinal polypeptide (VIP) from rat spinal cord: modulation by alpha 2 agonists. Peptides. 14, 371-378.
171. Talley, E. M., Cribbs, L. L., Lee, J. H., Daud, A., Perez-Reyes, E. and Bayliss, D. A., 1999. Differential distribution of three members of a gene family encoding low voltage-activated (T-type) calcium channels. J Neurosci. 19, 1895-1911.
172. Todd, A. J., 1996. GABA and glycine in synaptic glomeruli of the rat spinal dorsal horn. Eur J Neurosci. 8, 2492-2498.
173. Todd, A. J., 2002. Anatomy of primary afferents and projection neurones in the rat spinal dorsal horn with particular emphasis on substance P and the neurokinin 1 receptor. Exp Physiol. 87, 245-249.
174. Todd, A. J. and Lochhead, V., 1990. GABA-like immunoreactivity in type I glomeruli of rat substantia gelatinosa. Brain Res. 514, 171-174.
175. Todd, A. J. and McKenzie, J., 1989. GABA-immunoreactive neuronsin the dorsal horn of the rat spinal cord. Neuroscience. 31, 799-806.
176. Tognetto, M., Amadesi, S., Harrison, S., Creminon, C., Trevisani, M., Carreras, M., Matera, M., Geppetti, P. and Bianchi, A., 2001. Anandamide excites central terminals of dorsal root ganglion neurons via vanilloid receptor-1 activation. J Neurosci. 21, 1104-1109.
177. Too, H. P. and Maggio, J. E., 1991. Immunocytochemical localization of neuromedin K (neurokinin B) in rat spinal ganglia and cord. Peptides. 12, 431-443.
178. Trafton, J. A., Abbadie, C. and Basbaum, A. I., 2001. Differential contribution of substance P and neurokinin A to spinal cord neurokinin-1 receptor signaling in the rat. J Neurosci. 21, 3656-3664.
179. Trafton, J. A., Abbadie, C., Marchand, S., Mantyh, P. W. and Basbaum, A. I., 1999. Spinal opioid analgesia: how critical is the regulation of substance P signaling? J Neurosci. 19, 9642-9653.
180. Trevisani, M., Siemens, J., Materazzi, S., Bautista, D. M., Nassini, R., Campi, B., Imamachi, N., Andre, E., Patacchini, R., Cottrell, G. S., Gatti, R., Basbaum, A. I., Bunnett, N. W., Julius, D. and Geppetti, P., 2007. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci USA. 104, 13519-13524.
181. Tuchscherer, M. M. and Seybold, V. S., 1985. Immunohistochemical studies of substance P, cholecystokinin-octapeptide and somatostatin in dorsal root ganglia of the rat. Neuroscience. 14, 593-605.
182. Urban, L., Thompson, S. W. and Dray, A., 1994. Modulation of spinal excitability: co-operation between neurokinin and excitatory amino acid neurotransmitters. Trends Neurosci. 17, 432-438.
183. Urban, L. A. and Fox, A. J., 2000. NK1 receptor antagonists-are they really without effect in the pain clinic? Trends Pharmacol Sci. 21, 462-464; author reply 465.
184. Vasko, M. R., Campbell, W. B. and Waite, K. J., 1994. Prostaglandin E2 enhances bradykininstimulated release of neuropeptides from rat sensory neurons in culture. J Neurosci. 14, 4987-4997.
185. Vedder, H. and Otten, U., 1991. Biosynthesis and release of tachykinins from rat sensory neurons in culture. J Neurosci Res. 30, 288-299.
186. Vierck, C. J., Jr., Kline, R. H. and Wiley, R. G., 2003. Intrathecal substance p-saporin attenuates operant escape from nociceptive thermal stimuli. Neuroscience. 119, 223-232.
187. von Euler, U. S. and Gaddum, J. H., 1931. An unidentified depressor substance in certain tissue extracts. J Physiol. 72, 74-87.
188. Wang, H., Kohno, T., Amaya, F., Brenner, G. J., Ito, N., Allchorne, A., Ji, R. R. and Woolf, C. J., 2005. Bradykinin produces pain hypersensitivity by potentiating spinal cord glutamatergic synaptic transmission. J Neurosci. 25, 7986-7992.
189. Werry, E. L., Liu, G. J. and Bennett, M. R., 2006. Glutamate-stimulated ATP release from spinal cord astrocytes is potentiated by substance P. J Neurochem. 99, 924-936.
190. Wick, E. C., Pikios, S., Grady, E. F. and Kirkwood, K. S., 2006. Calcitonin gene-related peptide partially mediates nociception in acute experimental pancreatitis. Surgery. 139, 197-201.
191. Wilcox, G. L., 1988. Pharmacological studies of grooming and scratching behavior elicited by spinal substance P and excitatory amino acids. Ann NY Acad Sci. 525, 228-236.
192. Yaksh, T. L., Jessell, T. M., Gamse, R., Mudge, A. W. and Leeman, S. E., 1980. Intrathecal morphine inhibits substance P release from mammalian spinal cord in vivo. Nature. 286, 155-157.
193. Yamamoto, T. and Yaksh, T. L., 1991. Stereospecific effects of a nonpeptidic NK1 selective antagonist, CP-96, 345: antinociception in the absence of motor dysfunction. Life Sci. 49, 1955-1963.
194. Yamamoto, T. and Yaksh, T. L., 1992. Effects of in trathecal capsaicin andan NK-1 antagonist, CP, 96-345, on the thermal hyperalgesia observed following unilateral constriction of the sciatic nerve in the rat. Pain. 51, 329-334.
195. Yamasaki, H., Kubota, Y., Takagi, H. and Tohyama, M., 1984. Immunoelectronmicroscopic study on the fine structure of substance-P-containing fibers in the taste buds of the rat. J Comp Neurol. 227, 380-392.
196. Yang, X. D., Liu, Z., Liu, H. X., Wang, L. H., Ma, C. H. and Li, Z. Z., 2007. Regulatory effect of nerve growth factor on release of substance P in cultured dorsal root ganglion neurons of rat. Neurosci Bull. 23, 215-220.
197. Yoshimura, M. and North, R. A., 1983. Substantia gelatinosa neurones hyperpolarized in vitro by enkephalin. Nature. 305, 529-530.
198. Zaratin, P., Angelici, O., Clarke, G. D., Schmid, G., Raiteri, M., Carita, F. and Bonanno, G., 2000. NK3 receptor blockade prevents hyperalgesia and the associated spinal cord substance P release in monoarthritic rats. Neuropharmacology. 39, 141-149.
199. Zeitz, K. P., Guy, N., Malmberg, A. B., Dirajlal, S., Martin, W. J., Sun, L., Bonhaus, D. W., Stucky, C. L., Julius, D. and Basbaum, A. I., 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.
200. Zeng, D. W. and Lynch, K. R., 1991. Distribution of alpha 2-adrenergic receptor mRNAs in the rat CNS. Brain Res Mol Brain Res. 10, 219-225.
201. Zerari, F., Karpitskiy, V., Krause, J., Descarries, L. and Couture, R., 1998. Astroglial distribution of neurokinin-2 receptor immunoreactivity in the rat spinal cord. Neuroscience. 84, 1233-1246.
202. Zhang, X., Bao, L., Arvidsson, U., Elde, R. and Hokfelt, T., 1998. Localization and regulation of the delta-opioid receptor in dorsal root ganglia and spinal cord of the rat and monkey: evidence for association with the membrane of large dense-core vesicles. Neuroscience. 82, 1225-1242.
203. Zhou, X. F. and Rush, R. A., 1996. Endogenous brain-derived neurotrophic factor is anterogradely transported in primary sensory neurons. Neuroscience. 74, 945-953.
204. Zimmer, A., Zimmer, A. M., Baffi, J., Usdin, T., Reynolds, K., Konig, M., Palkovits, M. and Mezey, E., 1998. Hypoalgesia in mice with a targeted deletion of the tachykinin 1 gene. Proc Natl Acad Sci USA. 95, 2630-2635.
205. Zygmunt, P. M., Petersson, J., Andersson, D. A., Chuang, H., Sorgard, M., Di Marzo, V., Julius, D. and Hogestatt, E. D., 1999. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 400, 452-457.