Targeting the cholinergic system as a therapeutic strategy for the treatment of pain

Neuropharmacology

Volumn 53, Issue 2, 2007, Pages 197-206

  Jones, Philip G ^a   Dunlop, John ^a  

^a PFIZER INC   (United States)

Author keywords

Acetylcholine; Acetylcholinesterase; Muscarinic receptor; Nicotinic receptor; Pain

Indexed keywords

1,1 DIMETHYL 4 PHENYLPIPERAZINIUM; 3 (2 AZETIDINYLMETHOXY)PYRIDINE; 3 (3 HEXYLTHIO 2 PYRAZINYLOXY) 1 AZABICYCLO[2.2.1]HEPTANE; 5 (2 AZETIDINYLMETHOXY) 2 CHLOROPYRIDINE; ACETYLCHOLINE; ALFENTANIL; ALPHA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; ANTISENSE OLIGONUCLEOTIDE; ARECAIDINE; ATROPINE; BENZYL[3 [[1 (3,4 DICHLOROPHENYL)ETHYL]AMINO] 2 HYDROXYPROPYL]PHOSPHINIC ACID; BETHANECOL; CARBACHOL; CHOLINERGIC RECEPTOR STIMULATING AGENT; CHOLINESTERASE INHIBITOR; CLONIDINE; EPIBATIDINE; METHYLSCOPOLAMINE; MORPHINE; MUSCARINIC AGENT; N METHYL 4 (3 PYRIDINYL) 3 BUTENAMINE; NEOSTIGMINE; NICOTINIC AGENT; OXOTREMORINE; OXOTREMORINE M; PHENTOLAMINE; PHYSOSTIGMINE; STREPTOZOCIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VEDACLIDINE;

ALLODYNIA; ANALGESIA; ANTINOCICEPTION; CHOLINERGIC SYSTEM; DIABETIC NEUROPATHY; DRUG ANTAGONISM; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENTIATION; DRUG TARGETING; ENZYMATIC DEGRADATION; GASTROINTESTINAL SYMPTOM; HEART RATE; HUMAN; HYDROLYSIS; LOW DRUG DOSE; NEUROPATHIC PAIN; NONHUMAN; OSTEOARTHRITIS; PAIN; PRIORITY JOURNAL; REVIEW; SALIVATION DISORDER; SEIZURE; SIDE EFFECT; TACHYCARDIA; UNSPECIFIED SIDE EFFECT;

ACETYLCHOLINE; ACETYLCHOLINESTERASE; ANIMALS; HUMANS; PAIN; RECEPTORS, CHOLINERGIC;

EID: 34547552883     PISSN: 00283908     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2007.04.002     Document Type: Review

References (98)

1. Abe K., Taguchi K., Kato M., Utsunomiya I., Chikuma T., Hojyo H., and Miyatake T. Characterization of muscarinic receptor subtypes in the rostral ventrolateral medulla and effects on morphine-induced antinociception in rats. European Journal of Pharmacology 465 (2003) 237-249
2. Almeida R.A., Lauretti G.R., and Mattos A.L. Low-dose intrathecal neostigmine enhanced the analgesic effect of intrathecal morphine following gynecologic surgery. Anesthesiology 98 (2003) 495-498
3. Bannon A.W., Decker M.W., Holladay M.W., Curzon P., Donnelley-Roberts D., Puttfarcken P.S., Bitner R.S., Diaz A., Dickenson A.H., Porsolt R.D., Williams M., and Arneric S.P. Broad-spectrum, non-opioid analygesic activity by selective modulation of neuronal nicotinic acetylcholine receptors. Science 279 (1998) 77-81
4. Bannon A.W., Decker M.W., Curzon P., Buckley M.J., Kim D.J.B., Radek R.J., Lynch J.K., Wasicak J.T., Lin N.H., Arnold W.H., Holladay M.W., Williams M., and Arneric S.P. ABT-594 [(R)-5-2(azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective antinociceptive agent acting via neuronal nicotinic acetylcholine receptors: II. in vivo characterization. Journal of Pharmacology and Experimental. Therapeutics 285 (1998) 787-794
5. Berkley K.J. Sex difference in pain. Behavioural Brain Sciences 20 (1997) 371-382
6. Bernardini N., Levey A.I., and Augusti-Tocco G. Rat dorsal root ganglia express M1-M4 muscarinic receptor proteins. Journal of the Peripheral Nervous System 4 (1999) 222-232
7. Bernardini N., Sauer S.K., Haberberger R., Fischer M.J.M., and Reeh P.W. Excitatory nicotinic and desensitizing muscarinic (M2) effects on C-nociceptors in isolated rat skin. Journal of Neuroscience 21 (2001) 3295-3302
8. Bernardini N., Roza C., Sauer S.K., Gomeza J., Wess J., and Reeh P.W. Muscarinic M2 receptors on peripheral nerve endings: a molecular target of antinociception. Journal of Neuroscience 22 RC229 (2002) 1-5
9. Bitner R.S., Nikkel A.L., Curzon P., Donnelly-Roberts D.L., Puttfarcken P.S., Namovic M., Jacobs I.C., Meyer M.D., and Decker M.W. Reduced nicotinic receptor-mediated antinociception following in vivo antisense knock-down in rat. Brain Research 871 (2000) 66-74
10. Borovikova L.V., Ivanova S., Zhang M., Yang H., Botchkina G.I., Watkins L.R., Wang H., Abumrad N., Eaton J.W., and Tracey K.J. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405 (2000) 458-462
11. Bouaziz H., Tong C., and Eisenach J.C. Postoperative analgesia from intrathecal neostigmine in sheep. Anesthesia and Analgesia 80 (1995) 1140-1144
12. Brennan T.J., Vandermeulen E.P., and Gebhart G.F. Characterization of a rat model of incisional pain. Pain 64 (1996) 493-501
13. Carroll F.I., Lee J.R., Navarro H.A., Ma W., Brieaddy L.E., Abraham P., Damaj M.I., and Martin B.R. Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′,3′-disubstituted 5′-pyridinyl)-7-azabicyclo[2.2.1]heptanes: epibatidine analogues. Journal of Medicinal Chemistry 45 (2002) 4755-4761
14. Caulfield M.P., and Birdsall N.J.M. International Union of Pharmacology XVII. Classification of muscarinic acetylcholine receptors. Pharmacological Reviews 50 (1998) 279-290
15. Chen S.R., and Pan H.L. Up-regulation of spinal muscarinic receptors and increased antinociceptive effect of intrathecal muscarine in diabetic rats. Journal of Pharmacology and Experimental Therapeutics 307 (2003) 676-681
16. Chen S.-R., Khan G.M., and Pan H.-L. Antiallodynic effect of intrathecal neostigmine is mediated by spinal nitric oxide in a rat model of diabetic neuropathic pain. Anesthesiology 95 (2001) 1007-1012
17. Chiang C.-Y., and Zhuo M. Evidence for the involvement of a descending cholinergic pathway in systemic morphine analgesia. Brain Research 478 (1989) 293-300
18. Chiari A., Tobin J.R., Pan H.-L., Hood D.D., and Eisenach J.C. Sex differences in cholinergic analgesia I: a supplemental nicotinic mechanism in normal females. Anesthesiology 91 (1999) 1447-1454
19. Costigan M., Befort K., Karchewski L., Griffin R.S., D'Urso D., Allchorne A., Sitarski J., Mannion J.W., Pratt R.E., and Woolf C. Replicate high-density rat genome oligonucleotide microarrays reveal hundreds of regulated genes in the dorsal root ganglion after peripheral nerve injury. BMC Neuroscience 3 (2002) 16
20. Damaj M.I., Creasy K.R., Grove A.D., Rosecrans J.A., and Martin B.R. Pharmacological effects of epibatidine optical enantiomers. Brain Research 664 (1994) 34-40
21. Damaj M.I., Fei-Yin M., Duket M., Glassco W., Glennon R.A., and Martin B.R. Antinociceptive responses to nicotinic acetylcholine receptor ligands after systemic and intrathecal administration. Journal of Pharmacology and Experimental Therapeutics 284 (1998) 1058-1065
22. Damaj M.I., Meyer E.M., and Martin B.R. The antinociceptive effects of α7 nicotinic agonists in an acute pain model. Neuropharmacology 39 (2000) 2785-2791
23. Davis L., Pollock L.J., and Stone T.T. Visceral pain. Surgery. Gynecology and Obstetrics 55 (1932) 418-427
24. Decker M.W., Bannon A.W., Buckley M.J., Kim D.J.B., Holladay M.W., Ryther K.B., Lin N.H., Wasicak J.T., Williams M., and Arneric S.P. Antinociceptive effects of the novel neuronal nicotinic acetylcholine receptor agonist, ABT-594, in mice. European Journal of Pharmacology 346 (1998) 23-33
25. Detweiler D.J., Eisenach J.C., Tong C., and Jackson C. A cholinergic interaction in alpha 2 adrenoceptor-mediated antinociception in sheep. Journal of Pharmacology and Experimental Therapeutics 265 (1993) 536-542
26. Di-Cheng Z., Tun X., and Ming-Zhi S. The effects of acetylcholine on the electrical activities of pain neurons in nucleus parafascicularis of thalamus and midbrain reticular formation in rats. Acta Physiologica Sinica 40 (1988) 326-334
27. Donnelly-Roberts D.L., Puttfarcken P.S., Kuntzweiler T.A., Briggs C.A., Anderson D.J., Campbell J.E., Piattoni-Kaplan M., McKenna D.G., Wasicak J.T., Holladay M.W., Williams M., and Arneric S.P. ABT-594 [(R)-5-(2-Azetidinylmethoxy)-2-chloropyridine]: a novel, orally effective analgesic acting via neuronal nicotinic acetylcholine receptors: I. In vitro characterization. Journal of Pharmacology and Experimental Therapeutics 285 (1998) 777-786
28. Dube G.R., Kohlhaas K.L., Reuter L.E., Surowy C.S., Meyer M.D., and Briggs C.A. Loss of functional neuronal nicotinic receptors in dorsal root ganglion neurons in a rat model of neuropathic pain. Neuroscience Letters 376 (2005) 29-34
29. Duflo F., Boselli E., Ryvlin P., and Chassard D. Spinal muscarinic and nicotinic subtypes activated by clonidine in postincisional pain. Anesthesiology 103 (2005) 1253-1258
30. Dussor G.O., Helesic G., Hargreaves K.M., and Flores C.M. Cholinergic modulation of nociceptive responses in vivo and neuropeptide release in vitro at the level of the primary sensory neuron. Pain 107 (2004) 22-32
31. Duttaroy A., Gomeza J., Gan J.-W., Siddiqui N., Basile A.S., Harman W.D., Smith P.L., Felder C.C., Levey A.I., and Wess J. Evaluation of muscarinic agonist-induced analgesia in muscarinic acetylcholine receptor knockout mice. Molecular Pharmacology 62 (2002) 1084-1093
32. Eisenach J.C., and Gebhart G.F. Intrathecal amitriptyline: antinociceptive interactions with intravenous morphine and intrathecal clonidine, neostigmine, and carbamylcholine in rats. Anesthesiology 83 (1995) 1036-1045
33. Eisenach J.C., Detweiler D.J., Tong C., D'Angelo R., and Hood D.D. Cerebrospinal fluid norepinephrine and acetylcholine concentrations during acute pain. Anesthiology and Analgesia 82 (1996) 621-626
34. Eisenach J.C., Hood D.D., and Curry R. Phase I human safety assessment of intrathecal neostigmine containing methyl- and propylparabens. Anesthiology and Analgesia 85 (1997) 842-846
35. Ellis J.L., Harman D., Gonzalez J., Spera M.L., Liu R., Shen T.Y., Wypij D.M., and Zuo F. Development of muscarinic analgesics derived from epibatidine: role of the M4 receptor subtype. Journal of Pharmacology and Experimental Therapeutics 288 (1999) 1143-1150
36. Galeotti N., Bartolini A., and Ghelardini C. The phospholipase C-IP3 pathway is involved in muscarinic antinociception. Neuropsychopharmacology 28 (2003) 888-897
37. Galeotti N., Bartolini A., and Ghelardini C. Ryanodine receptors are involved in muscarinic antinociception in mice. Behavioural Brain Research 164 (2005) 165-171
38. Ghelardini C., Galeotti N., and Bartolini A. Loss of muscarinic antinociception by antisense inhibition of M1 receptors. British Journal of Pharmacology 129 (2000) 1633-1640
39. Gomeza J., Shannon H., Kostenis E., Felder C., Zhang L., Brodkin J., Grinberg A., Sheng H., and Wess J. Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice. Proceedings of the National Academy of Sciences USA 96 (1999) 1692-1697
40. Grant G.J., Piskoun B., and Bansinath M. Intrathecal administration of liposomal neostigmine prolongs analgesia in mice. Anaesthesiologica Scandinavica 46 (2002) 90-94
41. Guimaraes A.P., and Prado W.A. Antinociceptive effects of carbachol microinjected into different portions of the mesencephalic periaqueductal gray matter of the rat. Brain Research 647 (1994) 220-230
42. Guimaraes A.P.C., Guimaraes F.S., and Prado W.A. Modulation of carbachol-induced antinociception from the rat periaqueductal gray. Brain Research Bulletin 51 (2000) 471-478
43. Harte S.E., Hoot M.R., and Borszcz G.S. Involvement of the intralaminar parafascicular nucleus in muscarinic-induced antinociception in rats. Brain Research 1019 (2004) 152-161
44. Hoglund A.U., and Baghdoyan H.A. M2, M3 and M4, but not M1, muscarinic receptor subtypes are present in rat spinal cord. Journal of Pharmacology and Experimental Therapeutics 281 (1997) 470-477
45. Honda K., Harada A., Takano Y., and Kamiya H. Involvement of M3 muscarinic receptors of the spinal cord in formalin-induced nociception in mice. Brain Research 859 (2000) 38-44
46. Hood D.D., Eisenach J.C., and Tuttle R. Phase I safety assessment of intrathecal neostigmine methylsulfate in humans. Anesthesiology 82 (1995) 331-343
47. Hood D.D., Mallak K.A., Eisenach J.C., and Tong C. Interaction between intrathecal neostigmine and epidural clonidine in human volunteers. Anesthesiology 85 (1996) 315-325
48. Hood D.D., Mallak K.A., James R.L., Tuttle R., and Eisenach J.C. Enhancement of analgesia from systemic opioid in humans by spinal cholinesterase inhibition. Journal of Pharmacology and Experimental Therapeutics 282 (1997) 86-92
49. Hwang J.-H., Hwang K.-S., Leem J.-K., Park P.-H., Han S.-M., and Lee D.-M. The antiallodynic effects of intrathecal cholinesterase inhibitors in a rat model of neuropathic pain. Anesthesiology 90 (1999) 492-499
50. Iwamoto E.T., and Marion L. Characterization of the antinociception produced by intrathecally administered muscarinic agonists in rats. Journal of Pharmacology and Experimental Therapeutics 266 (1993) 329-338
51. Iyadomi M., Iyadomi I., Kumamoto E., Tomokuni K., and Yoshimura M. Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn. Pain 85 (2000) 385-393
52. Kim S.H., and Chung J.M. An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 50 (1992) 355-363
53. Koga K., Honda K., Ando S., Harasawa I., Kamiya H., and Takano Y. Intrathecal clonidine inhibits mechanical allodynia via activation of the spinal muscarinic M1 receptor in streptozotocin-induced diabetic mice. European Journal of Pharmacology 505 (2004) 75-82
54. Langley R.J., Kalra R., Mishra N.C., and Sopori M.L. Central but not the peripheral action of cholinergic compounds suppresses the immune system. Journal of Neuroimmunology 148 (2004) 140-145
55. Lavand'homme P.M., and Eisenach J.C. Sex differences in cholinergic analgesia II: differing mechanisms in two models of allodynia. Anesthesiology 91 (1999) 1454-1455
56. Lavand'homme P., Pan H.-L., and Eisenach J.C. Intrathecal neostigmine, but not sympathectomy, relieves mechanical allodynia in a rat model of neuropathic pain. Anesthesiology 89 (1998) 493-499
57. Lawand N.B., Lu Y., and Westlund K.N. Nicotinic cholinergic receptors: potential targets for inflammatory pain relief. Pain 80 (1999) 291-299
58. Li X., and Eisenach J.C. Nicotinic acetylcholine receptor regulation of spinal norepinephrine release. Anesthesiology 96 (2002) 1450-1456
59. B receptors in spinal glutamate release and cholinergic analgesia in rats. Journal of Physiology 543 (2002) 807-818
60. Livett B.G., Sandall D.W., Keays D., Down J., Gayler K.R., Satkunanathan N., and Khalil Z. Therapeutic applications of conotoxins that target the neuronal nicotininc acetylcholine receptor. Toxicon 48 (2006) 810-829
61. Lynch III J.J., Wade C.L., Mikusa J.P., Decker M.W., and Honore P. ABT-594 (a nicotinic acetylcholine agonist): anti-allodynia in a rat chemotherapy-induced pain model. European Journal of Pharmacology 509 (2005) 43-48
62. Marubio L.M., del Mar Arroyo-Jiminez M., Cordero-Erausquin M., Lena C., Le Novere N., de Kerchove d'Exaerde A., Huchet M., Imad Damaj M., and Changeux J.P. Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature 398 (1999) 805-810
63. Mulugeta E., El-Bakri N., Karlsson E., Elhassan A., and Adem A. Loss of muscarinic M4 receptors in spinal cord of arthritic rats: implications for a role of M4 receptors in pain response. Brain Research 982 (2003) 284-287
64. Naguib M., and Yaksh T.L. Characterization of muscarinic receptor subtypes that mediate antinociception in the rat spinal cord. Anesthesiology and Analgesia 85 (1997) 847-853
65. Nishiyama T., Gyernek L., Trudell M.L., and Hanaoka K. Spinally mediated analgesic and receptor binding affinity of epibatidine analogs. European Journal of Pharmacology 470 (2003) 27-31
66. Nizri E., Hamra-Amitay Y., Sicsic C., Lavon I., and Brenner T. Anti-inflammatory properties of cholinergic up-regulation: a new role for acetylcholinesterase inhibitors. Neuropharmacology 50 (2006) 540-547
67. Nomura J., Hosoi T., Okuma Y., and Nomura Y. The presence and functions of muscarinic receptors in human T cells: the involvement in IL-2 and IL-2 receptor system. Life Sciences 72 (2003) 2121-2126
68. Papke R.L., Webster C., Lippiello P.M., Bencherif M., and Francis M.N. The activation and inhibition of human nicotinic acetylcholine receptor by RJR-2403 indicate a selectivity for the α4/β2 subtype. Journal of Neurochemistry 75 (2000) 204-216
69. Pavlov V.A., Ochani M., Gallowitsch-Puerta M., Ochani K., Huston J.M., Czura C.J., Al-Abed Y., and Tracey K.J. Central muscarinic cholinergic regulation of the systemic inflammatory response during endotoxemia. Proceedings of the National Academy of Sciences USA 103 (2006) 5219-5223
70. Prado W.A., and Segalla D.K. Antinociceptive effects of bethanechol or dimethylphenylpiperazinium in models of phasic or incisional pain in rats. Brain Research 1018 (2004) 272-282
71. Qian C., Li T., Shen T.Y., Libertine-Garahan L., Eckman J., Biftu T., and Ip S. Epibatidine is a nicotinic analgesic. European Journal of Pharmacology 250 (1993) R13-R14
72. Rao T.S., Correa L.D., Reid R.T., and Lloyd G.K. Evaluation of anti-nociceptive effects of neuronal nicotinic acetylcholine receptor (NAChR) ligands in the rat tail-flick assay. Neuropharmacology 35 (1996) 393-405
73. Sabb A.L., Husbands G.M., Tokolics J., Stein R.P., Tasse R.P., Boast C.A., Moyer J.A., and Abou-Gharbia M. Discovery of a highly potent, functionally-selective muscarinic M1 agonist, WAY-132983 using rational drug design and receptor modelling. Bioorganic Medincinal Chemistry Letters 9 (1999) 1895-1900
74. Sauerberg P., Olesen P.H., Sheardown M.J., Suzdak P.D., Shannon H.E., Bymaster F.P., Calligaro D.O., Mitch C.H., Ward J.S., and Swedberg M.D.B. Muscarinic agonists as analgesics. Antinociceptive activity versus M1 activity: SAR of alkylthio-TZTP's and related 1,2,5-thiadiazole analogs. Life Sciences 56 (1995) 807-814
75. Shannon H.E., Jones C.K., Li D.L., Peters S.C., Simmons R.M.A., and Iyengar S. Antihyperalgesic effects of the muscarinic receptor ligand vedaclidine in models involving central sensitization in rats. Pain 93 (2001) 221-227
76. Sheardown M.J., Shannon H.E., Swedberg M.D.B., Suzdak P.D., Bymaster F.P., Olesen P.H., Mitch C.H., Ward J.S., and Sauerberg P. M1 receptor agonist activity is not a requirement for muscarinic antinociception. Journal of Pharmacology and Experimental Therapeutics 281 (1997) 868-875
77. Spalding T.A., Trotter C., Skjaerbaek N., Messier T.L., Currier E.A., Burstein E.S., Li D., Hacksell U., and Brann M.R. Discovery of an ectopic activation site on the M(1) muscarinic receptor. Molecular Pharmacology 61 (2002) 1297-1302
78. Spande T.F., Garraffo H.M., Edwards M.W., Yeh H.J.C., Pannell L., and Daly. Epibatidine: a novel (chloropyridyl)azabicycloheptane with potent analgesic activity from the Ecuadorin poison frog. Journal of the American Chemical Society 114 (1992) 3475-3478
79. Sullivan J.P., Donnelly-Roberts D., Briggs C.A., Anderson D.J., Gopalakrishnan M., Piattoni-Kaplan M., Campbell J.E., McKenna D.G., Molinari E., Hettinger A.-M., Garvey D.S., Wasicak J.T., Holladay M.W., Williams M., and Arneric S.P. A-85380: in vitro pharmacological properties of a novel, high-affinity α4/β2 nicotinic acetylcholine receptor ligand. Neuropharmacology 35 (1996) 725-734
80. Sullivan, N.R., Cummons, T.A., Smith, V.A., Piesla, M.J., Strassle, B.W., Sun, S.C., Rogers, K.E., Leventhal, L., Jones, P.G., 2005, Pharmacological profile of WAY-132983, an M1/M4 preferring agonist, in preclinical models of neuropathic and inflammatory pain. 35th Annual Meeting for the Society of Neuroscience, Washington, DC, Nov 12-15, 2005.
81. Sullivan, N.R., Leventhal, L., Sun, S.-C., Cummons, T.A., Smith, V.A., Harrison, J., Lu, P., Uveges, A.J., Strassle, B.W., Piesla, M.J., Spangler, T.B., Ramdass, R., Barry, A., Schantz, J., Adams, W., Whiteside, G.T., Adedoyin, A., Jones, P.G. Pharmacological characterization of the muscarinic agonist, Way-132983, in in vitro and in vivo models of chronic pain. Journal of Pharmacology and Experimental Therapeutics, submitted for publication.
82. Tata A.M., Vilaro M.T., Agrati C., Biagioni S., Mengod G., and Augusti-Tocco G. Expression of muscarinic M2 receptor mRNA in dorsal root ganglia of neonatal rat. Brain Research 824 (1999) 63-70
83. Tata A.M., Vilaro M.T., and Mengod G. Muscarinic receptor subtypes expression in rat and chick dorsal root ganglia. Molecular Brain Research 82 (2000) 1-10
84. Tayebati S.K., Codini M., Gallai V., Mannino F., Parnetti L., Ricci A., Sarchielli P., and Amenta F. Radioligand binding assay of M1-M5 muscarinic cholinergic receptor subtypes in human peripheral blood lymphocytes. Journal of Neuroimmunology 99 (1999) 224-229
85. Tayebati S.K., El-Assouad D., Ricci A., and Amenta F. Immunochemical and immunocytochemical characterization of cholinergic markers in human peripheral blood lymphocytes. Journal of Neuroimmunology 132 (2002) 147-155
86. Vincler M., Wittenauer S., Parker R., Ellison M., Olivera B.M., and McIntosh J.M. Molecular mechanisms for analgesia involving specific antagonism of α9α10 nicotinic acetylcholine receptors. Proceedings of the National Academy of Sciences USA 103 (2006) 17880-17884
87. Wang H., Sun H., Della Penna K., Benz R.J., Xu J., Gerhold D.L., Holder D.J., and Koblan K.S. Chronic neuropathic pain is accompanied by global changes in gene expression and shares pathobiology with neurodegenerative diseases. Neuroscience 114 (2002) 529-546
88. Wang H., Yu M., Ochani M., Amella C.A., Tanovic M., Susarla S., Li J.H., Wang H., Yang H., Ulloa L., Al-Abed Y., Czura C.J., and Tracey K.J. Nicotinic acetylcholine receptor 7 subunit is an essential regulator of inflammation. Nature 421 (2003) 384-388
89. Wang Y., Su D.M., Wang R.-H., Liu Y., and Wang H. Antinociceptive effects of choline against acute and inflammatory pain. Neuroscience 132 (2005) 49-56
90. Wang X.L., Zhang H.-M., Li D.-P., Chen S.-R., and Pan H.-L. Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats. Journal of Physiology 571 (2006) 403-413
91. Wei J., Walton E.A., Milici A., and Buccafusco J.J. M1-M5 muscarinic receptor distribution in rat CNS by RT-PCR and HPLC. Journal of Neurochemistry 63 (1994) 815-821
92. Wess J., Duttaroy A., Gomeza J., Zhang W., Yamada M., Felder C.C., Bernardini N., and Reeh P.W. Muscarinic receptor subtypes mediating central and peripheral antinociception studied with muscarinic receptor knockout mice: a review. Life Sciences 72 (2003) 2047-2054
93. Wessler I., Kirkpatrick C.J., and Racke K. Non-neuronal acetylcholine, a locally acting molecule, widely distributed in biological systems: expression and function in humans. Pharmacology and Therapeutics 77 (1998) 59-79
94. Xiao H.S., Huang Q.H., Zhang F.X., Bao L., Lu Y.J., Guo C., Yang L., Huang W.J., Fu G., Xu S.H., Cheng X.P., Yan Q., Zhu Z.D., Zhang X., Chen Z., Han Z.G., and Zhang X. Identification of gene expression profile of dorsal root ganglion in the rat peripheral axotomy model of neuropathic pain. Proceedings of the National Academy of Sciences USA 99 (2002) 8360-8365
95. Yang L., Zhang F.X., Huang F., Lu Y.J., Li G.D., Bao L., Xiao H.S., and Zhang X. Peripheral nerve injury induces trans-synaptic modification of channels, receptors and signal pathways in rat dorsal spinal cord. European Journal of Neuroscience 19 (2004) 871-883
96. Zhang H.-M., Chen S.-R., Matsui M., Gautam D., Wess J., and Pan H.-L. Opposing functions of spinal M2, M3, and M4 receptor subtypes in regulation of GABAergic inputs to dorsal horn neurons revealed by muscarinic receptor knockout mice. Molecular Pharmacology 69 (2006) 1048-1055
97. Zhuo M., and Gebhart G.F. Spinal cholinergic and monaminergic receptors mediate descending inhibition from the nuclei reticularis gigantocellularis and giganocellularis pars alpha in the rat. Brain Research 535 (1990) 67-78
98. Zhuo M., and Gebhart G.F. Inhibition of a cutaneous nociceptive reflex by a noxious visceral stimulus is mediated by spinal cholinergic and descending serotonergic systems in the rat. Brain Research 585 (1992) 7-18