Endogenous Antinociceptive Ligands 525 Suarez C, Tornadu IG, Cristina C, Vela J, Iglesias AG, Libertun C, Diaz-Torga G, Becu-Villalobos D (2002) Angiotensin and calcium signaling in the pituitary and hypothalamus. Cell Mol Neurobiol 22:315–333 Succar R, Mitchell VA, Vaughan CW (2007) Actions of N-arachidonyl-glycine in a rat inflamma- tory pain model. Mol Pain 3:24 Sugden D (1983) Psychopharmacological effects of melatonin in mouse and rat. J Pharmacol Exp Ther 227:587–591 Sugiura T, Kishimoto S, Oka S, Gokoh M (2006) Biochemistry, pharmacology and physiology of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand. Prog Lipid Res 45: 405–446 Suh HW, Song DK, Choi YS, Kim YH (1996) Effects of intrathecally injected histamine recep- tor antagonists on the antinociception induced by morphine, beta-endorphin, and U50, 488H administered intrathecally in the mouse. Neuropeptides 30:485–490 Suh HW, Song D-K, Choi YS, Cheon S-H, Kim YH (1994) Differential effects of intrathecally injected galanin on antinociception induced by beta-endorphin and morphine administered intracerebroventricularly in mice. Neuropeptides 26:297–303 Sullivan AF, Kalso EA, McQuay HJ, Dickenson AH (1991) FLFQPQRF-amide modulates alpha 2-adrenergic antinociception in the rat dorsal horn in vivo. Brain Res 562:327–328 Sun YG, Chen Z-F (2007) A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord. Nature 448:700–703 Sun YG, Lundeberg T, Yu LC (2003) Involvement of endogenous beta-endorphin in antinocicep- tion in the arcuate nucleus of hypothalamus in rats with inflammation. Pain 104:55–63 Sun YG, Yu LC (2005) Interactions of galanin and opioids in nociceptive modulation in the arcuate nucleus of hypothalamus in rats. Regul Pept 124:37–43 Suplita II RL, Gutierrez T, Fegley D, Piomelli D, Hohmann AG (2006) Endocannabinoids at the spinal level regulate, but do not mediate, nonopioid stress-induced analgesia. Neuropharmacology 50:372–379 Suplita RL, Farthing JN, Gutierrez T, Hohmann AG (2005) Inhibition of fatty-acid amide hydrolase enhances cannabinoid stress-induced analgesia: sites of action in the dorsolateral periaqueductal gray and rostral ventromedial medulla. Neuropharmacology 49:1201–1209 Sutton LC, Fleshner M, Mazzeo R, Maier SF, Watkins LR (1994) A permissive role of corticos- terone in an opioid form of stress-induced analgesia: blockade of opiate analgesia is not due to stress-induced hormone release. Brain Res 663:19–29 Suzuki R, Rahman W, Hunt SP, Dickenson AH (2004) Descending facilitatory control of mechan- ically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury. Brain Res 1019:68–76 Swanson LW, McKellar S (1979) Distribution of oxytocin-stained and neurophysin-stained fibers in the spinal-cord of the rat and monkey. J Comp Neurol 188:87–106 Sweeney MI, White TD, Sawynok J (1987) Involvement of adenosine in the spinal antinociceptive effects of morphine and noradrenaline. J Pharmacol Exp Ther 243:657–665 Szabo B (2008) Pharmacology of cannabinoid receptors. Biotrend Rev 2:1–13 Szabo C (2007) Hydrogen sulphide and its therapeutic potential. Nat Rev Drug Discov 6:917–935 Szeto HH (2003) Dynorphin and the hypothalamo-pituitary-adrenal axis during fetal development. Life Sci 73:749–758 Szolcsanyi J (2000) Are cannabinoids endogenous ligands for the VR1 capsaicin receptor? Trends Pharmacol Sci 21:41–42 Szolcsanyi J (2004) Forty years in capsaicin research for sensory pharmacology and physiology. Neuropeptides 38:377–384 Szolcsanyi J, Sandor Z, Petho G, Varga A, Bolcskei K, Almasi R, Riedl Z, Hajos G, Czeh G (2004) Direct evidence for activation and desensitization of the capsaicin receptor by N-oleyldopamine on TRPV1-transfected cell, line in gene deleted mice and in the rat. Neurosci Lett 361:155–158 Taguchi H, Oishi K, Sakamoto S, Shingu K (2007) Intrathecal betamethasone for cancer pain in the lower half of the body: a study of its analgesic efficacy and safety. Br J Anaesth 98:385–389 526 G. Horvath Taiwo OB, Taylor BK (2002) Antihyperalgesic effects of intrathecal neuropeptide Y during inflammation are mediated by Y1 receptors. Pain 96:353–363 Taiwo YO, Levine JD (1992) Serotonin is a directly-acting hyperalgesic agent in the rat. Neuroscience 48:485–490 Takada M, Li ZK, Hattori T (1988) Single thalamic dopaminergic neurons project to both the neocortex and spinal cord. Brain Res 455:346–352 Takagi H, Shiomi H, Ueda H, Amano H (1979) A novel analgesic dipeptide from bovine brain is a possible Met-enkephalin releaser. Nature 282:410–412 Takeda D, Nakatsuka T, Papke R, Gu JG (2003) Modulation of inhibitory synaptic activity by a non-alpha4beta2, non-alpha7 subtype of nicotinic receptors in the substantia gelatinosa of adult rat spinal cord. Pain 101:13–23 Takemori AE, Portoghese PS (1993) Enkephalin antinociception in mice is mediated by delta1- and delta2-opioid receptors in the brain and spinal cord, respectively. Eur J Pharmacol 242:145–150 Takeshita N, Yamaguchi I (1997) Insulin attenuates formalin-induced nociceptive response in mice through a mechanism that is deranged by diabetes mellitus. Mol Brain Res 63:180–183 Tanabe M, Takasu K, Yamaguchi S, Kodama D, Ono H (2008) Glycine transporter inhibitors as a potential therapeutic strategy for chronic pain with memory impairment. Anesthesiology 108:929–937 Tanabe M, Tokuda Y, Takasu K, Ono K, Honda M, Ono H (2007) The synthetic TRH analogue taltirelin exerts modality-specific antinociceptive effects via distinct descending monoaminer- gic systems. Br J Pharmacol 150:403–414 Tang B, Ji Y, Traub RJ (2008) Estrogen alters spinal NMDA receptor activity via a PKA signaling pathway in a visceral pain model in the rat. Pain 137:540–549 Tao F, Tao YX, Zhao C, Dore S, Liaw WJ, Raja SN, Johns RA (2004) Differential roles of neuronal and endothelial nitric oxide synthases during carrageenan-induced inflammatory hyperalgesia. Neuroscience 128:421–430 Tao F, Tao Y-X, Mao P, Zhao C, Li D, Liaw W-J, Raja SN, Johns RA (2003) Intact carrageenan- induced thermal hyperalgesia in mice lacking inducible nitric oxide synthase. Neuroscience 120:847–854 Tashev R, Belcheva S, Milenov K, Belcheva I (2001) Antinociceptive effect of somatostatin microinjected into caudate putamen. Peptides 22:1079–1083 Tata AM, De Stefano ME, Srubek Tomassy G, Vilaro MT, Levey AI, Biagioni S (2004) Subpopulations of rat dorsal root ganglion neurons express active vesicular acetylcholine transporter. J Neurosci Res 75:194–202 Taylor BK, Joshi C, Uppal H (2003) Stimulation of dopamine D2 receptors in the nucleus accumbens inhibits inflammatory pain. Brain Res 987:135–143 Telleria-Diaz A, Ebersberger A, Vasquez E, Schache F, Kahlenbach J, Schaible HG (2008) Different effects of spinally applied prostaglandin D2 on responses of dorsal horn neurons with knee input in normal rats and in rats with acute knee inflammation. Neuroscience 156:184–192 Terashvili M, Tseng LF, Wu H, Narayanan J, Hart LM, Falck JR, Pratt PF, Harder DR (2008) Antinociception produced by 14,15-epoxyeicosatrienoic acid is mediated by the activation of beta-endorphin and Met-enkephalin in the rat ventrolateral periaqueductal gray. J Pharmacol Exp Ther 326:614–622 Than M, Nemeth J, Szilvassy Z, Pinter E, Helyes Z, Szolcsanyi J (2000) Systemic anti- inflammatory effect of somatostatin released from capsaicin-sensitive vagal and sciatic sensory fibers of the rat and guinea-pig. Eur J Pharmacol 399:251–258 Theodosiou M, Rush RA, Zhou XF, Hu D, Walker JS, Tracey DJ (1999) Hyperalgesia due to nerve damage: role of nerve growth factor. Pain 81:245–255 Thoburn KK, Hough LB, Nalwalk JW, Mischler SA (1994) Histamine-induced modulation of nociceptive responses. Pain 58:29–37 Thompson SW, Bennett DLH, Kerr BJ, Bradbury EJ, McMahon SB (1999) Brain-derived neu- rotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord. Proc Natl Acad Sci U S A 96:7714–7718 Endogenous Antinociceptive Ligands 527 Thurston CL, Campbell IG, Culhane ES, Carstens E, Watkins LR (1992) Characterization of intrathecal vasopressin-induced antinociception, scratching behavior, and motor suppression. Peptides 13:17–25 Todd AJ, Spike RC, Russell G, Johnston HM (1992) Immunohistochemical evidence that Met- enkephalin and GABA coexist in some neurones in rat dorsal horn. Brain Res 584:149–156 Tokunaga A, Saika M, Senba E (1998) 5-HT2A receptor subtype is involved in the thermal hyperalgesic mechanism of serotonin in the periphery. Pain 76:349–355 Tozaki-Saitoh H, Tsuda M, Miyata H, Ueda K, Kohsaka S, Inoue K (2008) P2Y12 receptors in spinal microglia are required for neuropathic pain after peripheral nerve injury. J Neurosci 28:4949–4956 Traversa U, Bombi G, Camaioni E, Macchiarulo A, Costantino G, Palmieri C, Caciagli F, Pellicciari R (2003) Rat brain guanosine binding site. Biological studies and pseudo-receptor construction. Bioorg Med Chem 11:5417–5425 Tribollet E, Duboisdauphin M, Dreifuss JJ, Barberis C, Jard S (1992) Oxytocin receptors in the central-nervous-system - distribution, development, and species-differences. Ann N Y Acad Sci 652:29–38 Trivedi P, Yu H, MacNeil DJ, Van der Ploeg LHT, Guan XM (1998) Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438:71–75 Tseng LF, Collins KA (1993) Spinal involvement of both dynorphin A and Met-enkephalin in the antinociception induced by intracerebroventriculary administered bremazocine but not morphine in the mouse. J Pharmacol Exp Ther 266:1430–1438 Tseng L-F, Narita M, Suganuma C, Mizoguchi H, Ohsawa M, Nagase H, Kampine JP (2000) Differential antinociceptive effects of endomorphin-1 and endomorphin-2 in the mouse. J Pharmacol Exp Ther 292:576–583 Tsuda M, Inoue K, Salter MW (2005) Neuropathic pain and spinal microglia: a big problem from molecules in ‘small’ glia. Trends Neurosci 28:101–107 Tu Y, Sun RQ, Willis WD (2004) Effects of intrathecal injections of melatonin analogs on capsaicin-induced secondary mechanical allodynia and hyperalgesia in rats. Pain 109:340–350 Tuboly G, Benedek G, Horvath G (2009) Selective disturbance of pain sensitivity after social isolation. Physiol Behav 96:18–22 Turski WA, Schwarcz R (1988) On the disposition of intrahippocampally injected kynurenic acid in the rat. Exp Brain Res 71:563–567 Uchida H, Mizuno K, Yoshida A, Ueda H (2003) Neurosteroid-induced hyperalgesia through a histamine release is inhibited by progesterone and p,p -DDE, an endocrine disrupting chemical. Neurochem Int 42:401–407 Ueda H, Shiomi H, Takagi H (1980) Regional distribution of a novel analgesic dipeptide kyotorphin (Tyr-Arg) in the rat brain and spinal cord. Brain Res 198:460–464 Ueda H, Yoshihara Y, Misawa H, Fukushima N, Katada T, Ui M, Takagi H, Satoh M (1989) The kyotorphin (tyrosine-arginine) receptor and a selective reconstitution with purified Gi, measured with GTPase and phospholipase C assays. J Biol Chem 264:3732–3741 Ulugol A, Dokmeci D, Guray G, Sapolyo N, Ozyigit F, Tamer M (2006) Antihyperalgesic, but not antiallodynic, effect of melatonin in nerve-injured neuropathic mice: possible involvements of the L-arginine-NO pathway and opioid system. Life Sci 78:1592–1597 Urban MO, Coutinho SV, Gebhart GF (1999) Biphasic modulation of visceral nociception by neurotensin in rat rostral ventromedial medulla. J Pharmacol Exp Ther 290:207–213 Urbanska EM, Chmielewski M, Kocki T, Turski WA (2000) Formation of endogenous glutamater- gic receptors antagonist kynurenic acid - differences between cortical and spinal cord slices. Brain Res 878:210–212 Usdin TB, Dobolyi A, Ueda H, Palkovits M (2003) Emerging functions for tuberoinfundibular peptide of 39 residues. Trends Endocrinol Metab 14:14–19 Vaccarino F, Guidotti A, Costa E (1987) Ganglioside inhibition of glutamate-mediated protein kinase C translocation in primary cultures of cerebellar neurons. Proc Natl Acad Sci U S A 84:8707–8711 528 G. Horvath Vale ML, Marques JB, Moreira CA, Rocha FA, Ferreira SH, Poole S, Cunha FQ, Ribeiro RA (2003) Antinociceptive effects of interleukin-4, -10, and -13 on the writhing response in mice and zymosan-induced knee joint incapacitation in rats. J Pharmacol Exp Ther 304:102–108 Vallone D, Picetti R, Borrelli E (2000) Structure and function of dopamine receptors. Neurosci Biobehav Rev 24:125–132 Van den Pol AN (1999) Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J Neurosci 19:3171–3182 Van Huysse JW, Leenen FH (1998) Role of endogenous brain “ouabain” in the sympathoexcitatory and pressor effects of sodium. Clin Exp Hypertens 20:657–667 Van Sickle MD, Duncan M, Kingsley PJ, Mouihate A, Urbani P, Mackie K, Stella N, Makriyannis A, Piomelli D, Davison JS, Marnett LJ, Di Marzo V, Pittman QJ, Patel KD, Sharkey KA (2005) Identification and functional characterization of brainstem cannabinoid CB2 receptors. Science 310:329–332 Van Steenwinckel J, Brisorgueil MJ, Fischer J, Verge D, Gingrich JA, Bourgoin S, Hamon M, Bernard R, Conrath M (2008) Role of spinal serotonin 5-HT2A receptor in 2 ,3 - dideoxycytidine-induced neuropathic pain in the rat and the mouse. Pain 137:66–80 Vanderah TW, Laughlin T, Lashbrook JM, Nichols ML, Wilcox GL, Ossipov MH, Malan TP, Porreca F (1996) Single intrathecal injections of dynorphin A or des-Tyr-dynorphins produce long-lasting allodynia in rats: blockade by MK-801 but not naloxone. Pain 68:275–281 Vanecek J (1998) Cellular mechanisms of melatonin action. Physiol Rev 78:687–721 Vanegas H, Schaible HG (2001) Prostaglandins and cyclooxygenases in the spinal cord. Prog Neurobiol 64:327–363 Vasquez E, Bar KJ, Ebersberger A, Klein B, Vanegas H, Schaible HG (2001) Spinal prostaglandins are involved in the development but not the maintenance of inflammation-induced spinal hyperexcitability. J Neurosci 21:9001–9008 Vaught JL, Pelley K, Costa LG, Setler P, Enna SJ (1985) A comparison of the antinociceptive responses to the GABA-receptor agonists THIP and baclofen. Neuropharmacology 24:211–216 Vecsei L, Beal MF (1991) Comparative behavioral and pharmacological studies with centrally administered kynurenine and kynurenic acid in rats. Eur J Pharmacol 196:239–246 Velligan DI, Ritch JL, Sui D, DiCocco M, Huntzinger CD (2002) Frontal systems behavior scale in schizophrenia: relationships with psychiatric symptomatology, cognition and adaptive function. Psychiatry Res 113:227–236 Vergnano AM, Ferrini F, Salio C, Lossi L, Baratta M, Merighi A (2008) The gastrointestinal hor- mone ghrelin modulates inhibitory neurotransmission in deep laminae of mouse spinal cord dorsal horn. Endocrinology 149:2306–2312 Vergnano AM, Salio C, Merighi A (2004) NK1 receptor activation leads to enhancement of inhibitory neurotransmission in spinal substantia gelatinosa neurons of mouse. Pain 112:37–47 Vergnano AM, Schlichter R, Poisbeau P (2007) PKC activation sets an upper limit to the functional plasticity of GABAergic transmission induced by endogenous neurosteroids. Eur J Neurosci 26:1173–1182 Verma A, Hirsch DJ, Glatt CE, Ronnett GV, Snyder SH (1993) Carbon-monoxide - a putative neural messenger. Science 259:381–384 Vincler M, Eisenach JC (2004) Plasticity of spinal nicotinic acetylcholine receptors following spinal nerve ligation. Neurosci Res 48:139–145 Vit JP, Clauw DJ, Moallem T, Boudah A, Ohara PT, Jasmin L (2006) Analgesia and hyperalgesia from CRF receptor modulation in the central nervous system of Fischer and Lewis rats. Pain 121:241–260 Vitte PA, Harthe C, Pevet P, Claustrat B (1990) Brain autoradiographic study in the golden hamster after intracarotid injection of [14C]melatonin. Neurosci Lett 110:1–5 Von Heijne M, Hao JX, Sollevi A, Xu XJ (1999) Intrathecal adenosine does not relieve allodynia- like behavior in spinally injured rats. NeuroReport 10:3247–3251 Vorwerk CK, Bonheur J, Kreutz MR, Dreyer EB, Laev H (1999) GM1 ganglioside administration protects spinal neurons after glutamate excitotoxicity. Restor Neurol Neurosci 14:47–51 Endogenous Antinociceptive Ligands 529 Vrinten DH, Adan RAH, Groen GJ, Gispen WH (2001) Chronic blockade of melanocortin receptors alleviates allodynia in rats with neuropathic pain. Anesth Analg 93:1572–1577 Vrinten DH, Gispen WH, Groen GJ, Adan RAH (2000) Antagonism of the melanocortin system reduces cold and mechanical allodynia in mononeuropathic rats. J Neurosci 20:8131–8137 Vuckovic S, Tomic M, Stepanovic-Petrovic R, Ugresic N, Prostran M, Boskovic B (2006) Peripheral antinociception by carbamazepine in an inflammatory mechanical hyperalgesia model in the rat: a new target for carbamazepine? J Pharmacol Sci 100:310–314 Vuong LAQ, Mitchell VA, Vaughan CW (2008) Actions of N-arachidonyl-glycine in a rat neuropathic pain model. Neuropharmacology 54:189–193 Walker JM, Hohmann AG (2005) Cannabinoid mechanisms of pain suppression. Handb Exp Pharmacol 168:509–554 Walker JM, Krey JF, Chen JS, Vefring E, Jahnsen JA, Bradshaw H, Huang SM (2005) Targeted lipidomics: fatty acid amides and pain modulation. Prostaglandins Other Lipid Mediat 77: 35–45 Walter L, Franklin A, Witting A, Moller T, Stella N (2002) Astrocytes in culture produce anandamide and other acylethanolamides. J Biol Chem 277:20869–20876 Walter L, Stella N (2003) Endothelin-1 increases 2-arachidonoyl glycerol (2-AG) production in astrocytes. Glia 44:85–90 Walter L, Stella N (2004) Cannabinoids and neuroinflammation. Br J Pharmacol 141:775–785 Wang D, Lundeberg T, Yu L-C (2000) Antinociceptive role of galanin in periaqueductal grey of rats with experimentally induced mononeuropathy. Neuroscience 96:767–771 Wang HR, Ng K, Hayes D, Gao XR, Forster G, Blaha C, Yeomans J (2004) Decreased amphetamine-induced locomotion and improved latent inhibition in mice mutant for the M5 muscarinic receptor gene found in the human 15q schizophrenia region. Neuropsychopharmacology 29:2126–2139 Wang JH, Simonavicius N, Wu XS, Swaminath G, Reagan J, Tian H, Ling L (2006a) Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem 281:22021–22028 Wang JL, Zhu CB, Cao XD, Wu GC (1999) Distinct effect of intracerebroventricular and intrathecal injections of nociceptin/orphanin FQ in the rat formalin test. Regul Pept 79:159–163 Wang JZ, Lundeberg T, Yu LC (2001a) Anti-nociceptive effect of neuropeptide Y in periaqueductal grey in rats with inflammation. Brain Res 893:264–267 Wang R, Guo W, Ossipov MH, Vanderah TW, Porreca F, Lai J (2003a) Glial cell line-derived neurotrophic factor normalizes neurochemical changes in injured dorsal root ganglion neurons and prevents the expression of experimental neuropathic pain. Neuroscience 121:815–824 Wang T, Li SR, Dai X, Peng YL, Chen Q, Wang R (2006b) Effects of melatonin on orphanin FQ/nociceptin-induced hyperalgesia in mice. Brain Res 1085:43–48 Wang X, Miyares RL, Ahern GP (2005a) Oleoylethanolamide excites vagal sensory neurones, induces visceral pain and reduces short-term food intake in mice via capsaicin receptor TRPV1. J Physiol 564:541–547 Wang XL, Zhang HM, Li DP, Hen SR, An HL (2006c) Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats. J Physiol 571:403–413 Wang Y, Pei G, Cai YC, Zhao ZQ, Wang JB, Jiang CL, Zheng ZC, Liu XY (1996) Human interleukin-2 could bind to opioid receptor and induce corresponding signal transduction. NeuroReport 8:11–14 Wang Y, Su DM, Wang RH, Liu Y, Wang H (2005b) Antinociceptive effects of choline against acute and inflammatory pain. Neuroscience 132:49–56 Wang YY, Wu SX, Liu XY, Wang W, Li YQ (2003b) Effects of c-fos antisense oligodeoxynu- cleotide on 5-HT-induced upregulation of preprodynorphin, preproenkephalin, and glutamic acid decarboxylase mRNA expression in cultured rat spinal dorsal horn neurons. Biochem Biophys Res Commun 309:631–636 Wang Z, Gardell LR, Ossipov MH, Vanderah TW, Brennan MB, Hochgeschwender U, Hruby VJ, Malan TP Jr, Lai J, Porreca F (2001b) Pronociceptive actions of dynorphin maintain chronic neuropathic pain. J Neurosci 21:1779–1786 530 G. Horvath Watanabe S, Kuwaki T, Yanagisawa M, Fukuda Y, Shimoyama M (2004) Persistent pain and stress activate pain-inhibitory orexin pathways. NeuroReport 16:5–8 Webb TI, Lynch JW (2007) Molecular pharmacology of the glycine receptor chloride channel. Curr Pharm Des 13:2350–2367 Webster VAD, Griffiths EC, Slater P (1983) Antinociceptive effects of thyrotrophin-releasing hormone and its analogues in the rat periaqueductal grey region. Neurosci Lett 42:67–70 Wei H, Panula P, Pertovaara A (1998) A differential modulation of allodynia, hyperalgesia and nociception by neuropeptide FF in the periaqueductal gray of neuropathic rats: interactions with morphine and naloxone. Neuroscience 86:311–319 Wei H, Panula P, Pertovaara A (2001) Modulation of pain by [1DMe]NPYF, a stable analogue of neuropeptide FF, in neuropathic rats. Brain Res 900:234–243 Weil-Fugazza J, Godefroy F (1993) Dorsal and ventral dopaminergic innervation of the spinal cord: functional implications. Brain Res Bull 30:319–324 Welch SP, Cooper CW, Dewey WL (1986) Antinociceptive activity of salmon calcitonin injected intraventricularly in mice: modulation of morphine antinociception. J Pharmacol Exp Ther 237:54–58 Welch SP, Dewey WL (1990) The activity of several peptide fragments of parathyroid hormone, alone and in combination with salmon calcitonin and morphine, in antinociceptive tests in the mouse. J Pharmacol Exp Ther 252:140–146 Welch SP, Huffman JW, Lowe J (1998) Differential blockade of the antinociceptive effects of centrally administered cannabinoids by SR14176A. J Pharmacol Exp Ther 286:1301–1308 Wen HL, Mehal ZD, Ong BH, Ho WKK, Wen DYK (1985) Intrathecal administration of beta- endorphin and dynorphin-(1–13) for the treatment of intractable pain. Life Sci 37:1213–1220 Wess J (1996) Molecular biology of muscarinic acetylcholine receptors. Crit Rev Neurobiol 10:69–99 Wess J, Duttaroy A, Gomeza J, Zhang W, Yamada M, Felder CC, Bernardini N, Reeh PW (2003) Muscarinic receptor subtypes mediating central and peripheral antinociception studied with muscarinic receptor knockout mice: a review. Life Sci 72:2047–2054 Wess J, Eglen RM, Gautam D (2007) Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development. Nat Rev Drug Discov 6:721–733 Wiesenfeld-Hallin Z (1987) Intrathecal vasoactive intestinal polypeptide modulates spinal reflex excitability primarily to cutaneous thermal stimuli in rats. Neurosci Lett 80:293–297 Wiesenfeld-Hallin Z, Persson A (1984) Subarachnoid injection of salmon calcitonin does not induce analgesia in rats. Eur J Pharmacol 104:375–377 Wiesenfeld-Hallin Z, Xu XJ, Crawley JN, Hokfelt T (2005) Galanin and spinal nociceptive mechanisms: recent results from transgenic and knock-out models. Neuropeptides 39:207–210 Wiesenfeld-Hallin Z, Xu X-J, Langel Ü, Bedecs K, Bartfai T, Hokfelt T, Bartfai T (1992) Galanin- mediated control of pain: enhanced role after nerve injury. Proc Natl Acad Sci U S A 89: 3334–3337 Wikberg JE, Mutulis F (2008) Targeting melanonortin receptors: an approach to treat weight disorders and sexual dysfunction. Nat Rev Drug Discov 7:307–323 Wiklund L, Behzadi G, Kalen P, Headley PM, Nicolopoulos LS, Parsons CG, West DC (1988) Autoradiographic and electrophysiological evidence for excitatory amino acid transmission in the periaqueductal gray projection to nucleus raphe magnus in the rat. Neurosci Lett 93: 158–163 Wiles AL, Pearlman RJ, Rosvall M, Aubrey KR, Vandenberg RJ (2006) N-Arachidonyl-glycine inhibits the glycine transporter, GLYT2a. J Neurochem 99:781–786 Williams DW, Lipton JM, Giesecke AH (1986) Influence of centrally administered peptides on ear withdrawal from heat in the rabbit. Peptides 7:1095–1100 Williams FG, Beitz AJ (1990) Ultrastructural morphometric analysis of GABA-immunoreactive terminals in the ventrocaudal periaqueductal gray: analysis of the relationship of GABA ter- minals and the GABAA receptor to periaqueductal gray-raphe magnus projection neurons. J Neurocytol 19:686–696 Endogenous Antinociceptive Ligands 531 Willingale HL, Gardiner NJ, McLymont N, Giblett S, Grubb BD (1997) Prostanoids synthesized by cyclo-oxygenase isoforms in rat spinal cord and their contribution to the development of neuronal hyperexcitability. Br J Pharmacol 122:1593–1604 Willis WD Jr (1988) Dorsal horn neurophysiology of pain. Ann N Y Acad Sci 531:76–89 Willis WD, Westlund KN (1997) Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol 14:2–31 Wilson-Gerwing TD, Dmyterko MV, Zochodne DW, Johnston JM, Verge VMK (2005) Neurotrophin-3 suppresses thermal hyperalgesia associated with neuropathic pain and atten- uates transient receptor potential vanilloid receptor-1 expression in adult sensory neurons. J Neurosci 25:758–767 Wilson-Gerwing TD, Verge VMK (2006) Neurotrophin-3 attenuates galanin expression in the chronic constriction injury model of neuropathic pain. Neuroscience 141:2075–2085 Wirkner K, Sperlagh B, Illes P (2007) P2X(3) receptor involvement in pain states. Mol Neurobiol 36:165–183 Wise LE, Shelton CC, Cravatt BF, Martin BR, Lichtman AH (2007) Assessment of anandamide’s pharmacological effects in mice deficient of both fatty acid amide hydrolase and cannabinoid CB1 receptors. Eur J Pharmacol 557:44–48 Wittau N, Grosse R, Kalkbrenner F, Gohla A, Schultz G, Gudermann T (2000) The galanin receptor type 2 initiates multiple signaling pathways in small cell lung cancer cells by coupling to G(q), G(i) and G(12) proteins. Oncogene 19:4199–4209 Wood PB (2008) Role of central dopamine in pain and analgesia. Expert Rev Neurother 8: 781–797 Woolf CJ, Costigan M (1999) Transcriptional and posttranslational plasticity and the generation of inflammatory pain. Proc Natl Acad Sci U S A 96:7723–7730 Wu D, Doods H, Arndt K, Schindler M (2002) Development and potential of non-peptide antag- onists for calcitonin-gene-related peptide (CGRP) receptors: evidence for CGRP receptor heterogeneity. Biochem Soc Trans 30:468–473 Wu FS, Yang YC, Tsai JJ (1999a) Melatonin potentiates the GABAA receptor-mediated current in cultured chick spinal cord neurons. Neurosci Lett 260:177–180 Wu GY, Morris SM (1998) Arginine metabolism: nitric oxide and beyond. Biochem J 336:1–17 Wu X, Li HD, Ruan HZ, Wang J (1999b) Effects of intra-hippocampal injection of interleukin-2 on pain threshold and formaldehyde-induced substance P-like immunoreactivity in periaqueductal gray and spinal cord. Acta Pharmacol Sin 20:839–843 Xu H, Zhou KQ, Huang YN, Chen L, Xu TL (2004a) Taurine activates strychnine-sensitive glycine receptors in neurons of the rat inferior colliculus. Brain Res 1021:232–240 Xu IS, Grass S, Xu X-J, Wiesenfeld-Hallin Z (1998) On the role of galanin in mediating spinal flexor reflex excitability in inflammation. Neuroscience 85:827–835 Xu IS, Hao J-X, Xu X-J, Hokfelt T, Wiesenfeld-Hallin Z (1999a) The effect of intrathecal selective agonists on Y1 and Y2 neuropeptide Y receptors on the flexor reflex in normal axomized rats. Brain Res 833:251–257 Xu IS, Hashemi M, Calo G, Regoli D, Wiesenfeld-Hallin Z, Yacoub MH (1999b) Effects of intrathecal nocistatin on the flexor reflex and its interaction with orphanin FQ nociceptin. NeuroReport 10:3681–3684 Xu M, Petraschka M, McLaughlin JP, Westenbroek RE, Caron MG, Lefkowitz RJ, Czyzyk TA, Pintar JE, Terman GW, Chavkin C (2004b) Neuropathic pain activates the endogenous kappa opioid system in mouse spinal cord and induces opioid receptor tolerance. J Neurosci 24: 4576–4584 Xu W, Lundeberg T, Wang YT, Li Y, Yu L-C (2003) Antinociceptive effect of calcitonin gene-related peptide in the central nucleus of amygdala: activating opioid receptors through amygdala-periaqueductal gray pathway. Neuroscience 118:1015–1022 Xu XJ, Wiesenfeldhallin Z (1991) An analog of growth-hormone releasing-factor (GRF), (Ac- Try1, D-Phe2)-GRF-(1–29), specifically antagonizes the facilitation of the flexor reflex induced by intrathecal vasoactive-intestinal-peptide in rat spinal-cord. Neuropeptides 18:129–135 532 G. Horvath Xu Z, Chen S-R, Eisenach JC, Pan H-L (2000) Role of spinal muscarinic and nicotinic receptors in clonidine-induced nitric oxide release in a rat model of neuropathic pain. Brain Res 861: 390–398 Xu Z, Tong C, Eisenach JC (1996a) Acetylcholine stimulates the release of nitric oxide from rat spinal cord. Anesthesiology 85:107–111 Xu Z, Tong C, Pan H-L, Cerda SE, Eisenach JC (1997) Intravenous morphine increases release of nitric oxide from spinal cord by an alpha-adrenergic and cholinergic mechanism. J Neurophysiol 78:2072–2078 Xu ZQ, Shi TJ, Landry M, Hokfelt T (1996b) Evidence for galanin receptors in primary sensory neurones and effect of axotomy and inflammation. NeuroReport 8:237–242 Yagi J, Sumino R (1998) Inhibition of a hyperpolarization-activated current by clonidine in rat dorsal root ganglion neurons. J Neurophysiol 80:1094–1104 Yaksh TL (1989) Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. Pain 37:111–123 Yaksh TL, Farb DH, Leeman SE, Jessell TM (1979) Intrathecal capsaicin depletes substance P in the rat spinal cord and produces prolonged thermal analgesia. Science 206:481–483 Yamada K, Santo-Yamada Y, Wada K (2003) Stress-induced impairment of inhibitory avoidance learning in female neuromedin B receptor-deficient mice. Physiol Behav 78:303–309 Yamamoto T, Nozaki-Taguchi N, Chiba T (2002a) Analgesic effect of intrathecally adminis- tered orexin-A in the rat formalin test and in the rat hot plate test. Br J Pharmacol 137: 170–176 Yamamoto T, Saito O, Shono K, Aoe T, Chiba T (2003) Anti-mechanical allodynic effect of intrathecal and intracerebroventricular injection of orexin-A in the rat neuropathic pain model. Neurosci Lett 347:183–186 Yamamoto T, Sakashita Y (1999) Effect of nocistatin and its interaction with nociceptin/orphanin FQ on the rat formalin test. Neurosci Lett 262:179–182 Yamamoto T, Tatsuno I (1995) Antinociceptive effect of intrathecally administered pituitary adenylate cyclase activating peptide (PACAP) on the rat formalin test. Neurosci Lett 184:32–35 Yamamoto T, Wada T, Miyazaki R (2008) Analgesic effects of intrathecally administered 26RFa, an intrinsic agonist for GPR103, on formalin test and carrageenan test in rats. Neuroscience 157:214–222 Yamamoto T, Yaksh TL (1992) Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve. Excitatory amino acid antagonists. Pain 49:121–128 Yamamoto Y, Ono H, Ueda A, Shimamura M, Nishimura K, Hazato T (2002b) Spinorphin as an endogenous inhibitor of enkephalin-degrading enzymes: roles in pain and inflammation. Curr Protein Pept Sci 3:587–599 Yamazaki N, Umeno H, Kuraishi Y (1999) Involvement of brain serotonergic terminals in the antinociceptive action of peripherally applied calcitonin. Jpn J Pharmacol 81:367–374 Yan T, Liu BG, Du DP, Eisenach JC, Tong C (2007) Estrogen amplifies pain responses to uterine cervical distension in rats by altering transient receptor potential-1 function. Anesth Analg 104:1246–1250 Yanai K, Mobarakeh JI, Kuramasu A, Sakurada S (2003) Roles of histamine receptors in pain perception: a study using receptors gene knockout mice. Nippon Yakurigaku Zasshi 122: 391–399 Yang HY, Fratta W, Majane EA, Costa E (1985) Isolation, sequencing, synthesis, and pharmaco- logical characterization of two brain neuropeptides that modulate the action of morphine. Proc Natl Acad Sci U S A 82:7757–7761 Yang HY, Iadarola MJ (2006) Modulatory roles of the NPFF system in pain mechanisms at the spinal level. Peptides 27:943–952 Yang J (1994) Intrathecal administration of oxytocin-induced analgesia in low-back-pain involving the endogenous opiate peptide system. Spine 19:867–871 Endogenous Antinociceptive Ligands 533 Yang J, Chen JM, Liu WY, Song CY, Lin BC (2006) Through V2, not V1 receptor relat- ing to endogenous opiate peptides, arginine vasopressin in periaqueductal gray regulates antinociception in the rat. Regul Pept 137:156–161 Yang J, Yang Y, Chen JM, Xu HT, Liu WY, Wang CH, Lin BC (2007a) Arginine vasopressin is an important regulator in antinociceptive modulation of hypothalamic paraventricular nucleus in the rat. Neuropeptides 41:165–176 Yang J, Yang Y, Xu HT, Chen JM, Liu WY, Lin BC (2007b) Arginine vasopressin induces peri- aqueductal gray release of enkephalin and endorphin relating to pain modulation in the rat. Regul Pept 142:29–36 Yang K, Ma WL, Feng YP, Dong YX, Li YQ (2002) Origins of GABA(B) receptor-like immunoreactive terminals in the rat spinal dorsal horn. Brain Res Bull 58:499–507 Yang X-C, Reis DJ (1999) Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons. J Pharmacol Exp Ther 288: 544–549 Yang YH, Morand EF, Getting SJ, Paul-Clark M, Liu DL, Yona S, Hannon R, Buckingham JC, Perretti M, Flower RJ (2004) Modulation of inflammation and response to dexamethasone by annexin 1 in antigen-induced arthritis. Arthritis Rheum 50:976–984 Yang Z, Aubrey KR, Alroy I, Harvey RJ, Vandenberg RJ, Lynch JW (2009) Subunit-specific mod- ulation of glycine receptors by cannabinoids and N-arachidonyl-glycine. Biochem Pharmacol 76:1014–1023 Yao MZ, Gu JF, Wang JH, Sun LY, Lang MF, Liu J, Zhao ZQ, Liu XY (2002a) Interleukin-2 gene therapy of chronic neuropathic pain. Neuroscience 112:409–416 Yao MZ, Wang JH, Gu JF, Sun LY, Liu H, Zhao ZQ, Liu XY (2002b) Interleukin-2 gene has superior antinociceptive effects when delivered intrathecally. NeuroReport 13:791–794 Yeomans DC, Onyuksel H, Dagar S, Ikezaki H, Lu Y, Rubinstein I (2003) Conformation-dependent effects of VIP on nociception in rats. Peptides 24:617–622 Yesilyurt O, Dogrul A, Gul H, Seyrek M, Kusmez O, Ozkan Y, Yildiz O (2003) Topical cannabinoid enhances topical morphine antinociception. Pain 105:303–308 Yien HW, Chan JYH, Tsai HF, Lee TY, Chan SHH (1993) Participation of nucleus-reticularis gigantocellularis in the antinociceptive effect of angiotensin-III in the rat. Neurosci Lett 159:9–12 Yokogawa F, Kiuchi Y, Ishikaw Y, Otsuka N, Masuda Y, Oguchi K, Hosoyamada A (2002) An investigation of monoamine receptors involved in antinociceptive effects of antidepressants. Anesth Analg 95:163–168 Yonehara N, Yoshimura M (1999) Effect of nitric oxide on substance P release from the peripheral endings primary afferent neurons. Neurosci Lett 271:199–201 Yoshikawa M, Ito K, Maeda M, Akahori K, Takahashi S, Jin XL, Matsuda M, Suzuki T, Oka T, Kobayashi H, Hashimoto A (2007) Activation of supraspinal NMDA receptors by both D- serine alone or in combination with morphine leads to the potentiation of antinociception in tail-flick test of rats. Eur J Pharmacol 565:89–97 Young T, Wittenauer S, McIntosh JM, Vincler M (2008) Spinal alpha3beta2∗ nicotinic acetyl- choline receptors tonically inhibit the transmission of nociceptive mechanical stimuli. Brain Res 1229:118–124 Yu CX, Zhu CB, Xu SF, Cao XD, Wu GC (2000a) Selective MT(2) melatonin receptor antagonist blocks melatonin-induced antinociception in rats. Neurosci Lett 282:161–164 Yu C-X, Zhu C-B, Xu S-F, Cao X-D, Wu G-C (2000b) The analgesic effects of peripheral and central administration of melatonin in rats. Eur J Pharmacol 403:49–53 Yu LC, Weng XH, Wang JW, Lundeberg T (2003) Involvement of calcitonin gene-related peptide and its receptor in anti-nociception in the periaqueductal grey of rats. Neurosci Lett 349:1–4 Yu LC, Xu SL, Xiong W, Lundeberg T (2001) The effect of galanin on wide-dynamic range neuron activity in the spinal dorsal horn of rats. Regul Pept 101:179–182 Yu Y, Jawa A, Pan W, Kastin AJ (2004) Effects of peptides, with emphasis on feeding, pain, and behavior. A 5-year (1999–2003) review of publications in Peptides. Peptides 25:2257–2289 534 G. Horvath Zadina JE, Hackler L, Ge LJ, Kastin AJ (1997) A potent and selective endogenous agonist for the mu-opiate receptor. Nature 386:499–502 Zadina JE, Kastin AJ, Ge L-J, Hackler L (1994) Mu, delta, and kappa opiate receptor binding of Tyr-MIF-1 and of Tyr-W-MIF-1, its active fragments, and two potent a nalogs. Life Sci 55:PL461–PL466 Zadina JE, Kastin AJ, Kenigs V, Bruno C, Hackler L (1993) Prolonged analgesia after intracere- broventricular Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-Nh2). Neurosci Lett 155:220–222 Zadina JE, Kastin AJ, Kersh D, Wyatt A (1992) Tyr-MIF-1 and hemorphin can act as opiate agonists as well as antagonists in the guinea pig ileum. Life Sci 51:869–885 Zadina JE, Paul D, Gergen KA, Ge L-J, Hackler L, Kastin AJ (1996) Binding of Tyr-W-MIF-1 (Tyr-Pro-Trp-Gly-NH2) and related peptides to mu1 and mu 2 opiate receptors. Neurosci Lett 215:65–69 Zahn PK, Lansmann T, Berger E, Speckmann EJ, Musshoff U (2003) Gene expression and func- tional characterisation of melatonin receptors in the spinal cord of the rat: implications for pain modulation. J Pineal Res 35:24–31 Zamfirova R, Bocheva A, Dobrinova Y, Todorov S (2007) Study on the antinociceptive action of Tyr-K-MIF-1, a peptide from the MIF family. Auton Autacoid Pharmacol 27:93–98 Zeilhofer HU (2005) The glycinergic control of spinal pain processing. Cell Mol Life Sci 62: 2027–2035 Zeilhofer HU, Muth-Selbach U, Guhring H, Erb K, Ahmadi S (2000) Selective suppression of inhibitory synaptic transmission by nocistatin in the rat spinal cord dorsal horn. J Neurosci 20:4922–4929 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 Zeller CB, Marchase RB (1992) Gangliosides as modulators of cell function. Am J Physiol 262(6 Pt 1):C1341–C1355 Zeng Q, Wang S, Lim G, Yang L, Mao J, Sung B, Chang Y, Lim JA, Guo G, Mao J (2008) Exacerbated mechanical allodynia in rats with depression-like behavior. Brain Res 1200: 27–38 Zeng W, Dohi S, Shimonaka H, Asano T (1999) Spinal antinociceptive action of Na + -K + pump inhibitor ouabain and its interaction with morphine and lidocain in rats. Anesthesiology 90:500–508 Zhang J, Chen C (2008) Endocannabinoid 2-arachidonoylglycerol protects neurons by limiting COX-2 elevation. J Biol Chem 283:22601–22611 Zhang J, Hoffert C, Vu HK, Groblewski T, Ahmad S, O’Donnell D (2003a) Induction of CB2 receptor expression in the rat spinal cord of neuropathic but not inflammatory chronic pain models. Eur J Neurosci 17:2750–2754 Zhang XC, Zhang YQ, Zhao ZQ (2005) Involvement of nitric oxide in long-term potentiation of spinal nociceptive responses in rats. NeuroReport 16:1197–1201 Zhang Y, Malmberg AB, Sjolund B, Yaksh TL (1996) The effect of pituitary adenylate cyclase activating peptide (PACAP) on the nociceptive formalin test. Neurosci Lett 207: 187–190 Zhang YP, Lundeberg T, Yu LC (2000a) Interactions of galanin and morphine in the spinal antinociception in rats with mononeuropathy. Brain Res 852:485–487 Zhang YQ, Ji GC, Wu GC, Zhao ZQ (2003b) Kynurenic acid enhances electroacupuncture analgesia in normal and carrageenan-injected rats. Brain Res 966:300–307 Zhang YX, Lundeberg T, Yu LC (2000b) Involvement of neuropeptide Y and Y1 receptor in antinociception in nucleus raphe magnus of rats. Regul Pept 95:109–113 Zhao CS, Li BS, Zhao GY, Liu HX, Luo F, Wang Y, Tian JH, Chang JK, Han JS (1999) Nocistatin reverses the effect of orphanin FQ/nociceptin in antagonizing morphine analgesia. NeuroReport 10:297–299 . Distribution of orexin receptor mRNA in the rat brain. FEBS Lett 438:71–75 Tseng LF, Collins KA (1993) Spinal involvement of both dynorphin A and Met-enkephalin in the antinociception induced by intracerebroventriculary. oxytocin-stained and neurophysin-stained fibers in the spinal-cord of the rat and monkey. J Comp Neurol 188:87–106 Sweeney MI, White TD, Sawynok J (1987) Involvement of adenosine in the spinal antinociceptive effects. (2003) Involvement of endogenous beta-endorphin in antinocicep- tion in the arcuate nucleus of hypothalamus in rats with in ammation. Pain 104:55–63 Sun YG, Yu LC (2005) Interactions of galanin and