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PLOS ONE  2013 

Bilateral Descending Hypothalamic Projections to the Spinal Trigeminal Nucleus Caudalis in Rats

DOI: 10.1371/journal.pone.0073022

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Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C) remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG), into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project) than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project). These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.


[1]  Millan MJ (2002) Descending control of pain. Prog Neurobiol 66: 355-474. doi:10.1016/S0301-0082(02)00009-6. PubMed: 12034378.
[2]  Saper CB (2012) Hypothalamus. The Human Nervous System. Elsevier. pp. 549-572.
[3]  Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G (2007) Hypothalamic activation in spontaneous migraine attacks. Headache 47: 1418-1426. PubMed: 18052951.
[4]  Holle D, Katsarava Z, Obermann M (2011) The hypothalamus: specific or nonspecific role in the pathophysiology of trigeminal autonomic cephalalgias? Curr Pain Headache Rep 15: 101-107. doi:10.1007/s11916-010-0166-y. PubMed: 21128020.
[5]  May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ (1998) Hypothalamic activation in cluster headache attacks. Lancet 352: 275-278. doi:10.1016/S0140-6736(98)02470-2. PubMed: 9690407.
[6]  May A, Ashburner J, Büchel C, McGonigle DJ, Friston KJ et al. (1999) Correlation between structural and functional changes in brain in an idiopathic headache syndrome. Nat Med 5: 836-838. doi:10.1038/10561. PubMed: 10395332.
[7]  Leone M, Franzini A, Bussone G (2001) Stereotactic stimulation of posterior hypothalamic gray matter in a patient with intractable cluster headache. N Engl J Med 345: 1428-1429. doi:10.1056/NEJM200111083451915. PubMed: 11794190.
[8]  Leone M, Franzini A, Proietti Cecchini A, Bussone G (2013) Success, failure, and putative mechanisms in hypothalamic stimulation for drug-resistant chronic cluster headache. Pain 154: 89-94. doi:10.1016/j.pain.2012.09.011. PubMed: 23103434.
[9]  Schoenen J, Di Clemente L, Vandenheede M, Fumal A, De Pasqua V et al. (2005) Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain 128: 940-947. doi:10.1093/brain/awh411. PubMed: 15689358.
[10]  Fontaine D, Lanteri-Minet M, Ouchchane L, Lazorthes Y, Mertens P et al. (2010) Anatomical location of effective deep brain stimulation electrodes in chronic cluster headache. Brain 133: 1214-1223. doi:10.1093/brain/awq041. PubMed: 20237130.
[11]  Shigenaga Y, Matano S, Okada K, Sakai A (1973) The effects of tooth pulp stimulation in the thalamus and hypothalamus of the rat. Brain Res 63: 402-407. doi:10.1016/0006-8993(73)90113-3. PubMed: 4764310.
[12]  Morita N, Tamai Y, Tsujimoto T (1977) Unit responses activated by tooth pulp stimulation in lateral hypothalamic area of rat. Brain Res 134: 158-160. doi:10.1016/0006-8993(77)90934-9. PubMed: 912414.
[13]  Hamba M, Hisamitsu H, Muro M (1990) Nociceptive projection from tooth pulp to the lateral hypothalamus in rats. Brain. Res Bull 25: 355-364. doi:10.1016/0361-9230(90)90220-T.
[14]  Rudomin P, Malliani A, Borlone M, Zanchetti A (1965) Distribution of electrical responses to somatic stimuli in the diencephalon of the cat with special reference to the hypothalamus. Arch Ital Biol 103: 60-89. PubMed: 14277248.
[15]  Malick A, Jakubowski M, Elmquist JK, Saper CB, Burstein R (2001) A neurohistochemical blueprint for pain-induced loss of appetite. Proc Natl Acad Sci U S A 98: 9930-9935. doi:10.1073/pnas.171616898. PubMed: 11504950.
[16]  Ter Horst GJ, Meijler WJ, Korf J, Kemper RH (2001) Trigeminal nociception-induced cerebral Fos expression in the conscious rat. Cephalalgia 21: 963-975. doi:10.1046/j.1468-2982.2001.00285.x. PubMed: 11843868.
[17]  Benjamin L, Levy MJ, Lasalandra MP, Knight YE, Akerman S et al. (2004) Hypothalamic activation after stimulation of the superior sagittal sinus in the cat: a Fos study. Neurobiol Dis 16: 500-505. doi:10.1016/j.nbd.2004.03.015. PubMed: 15262261.
[18]  Iwata K, Kenshalo DR Jr., Dubner R, Nahin RL (1992) Diencephalic projections from the superficial and deep laminae of the medullary dorsal horn in the rat. J Comp Neurol 321: 404-420. doi:10.1002/cne.903210308. PubMed: 1506477.
[19]  Newman HM, Stevens RT, Apkarian AV (1996) Direct spinal projections to limbic and striatal areas: anterograde transport studies from the upper cervical spinal cord and the cervical enlargement in squirrel monkey and rat. J Comp Neurol 365: 640-658. doi:10.1002/(SICI)1096-9861(19960219)365:4. PubMed: 8742308.
[20]  Li JL, Kaneko T, Shigemoto R, Mizuno N (1997) Distribution of trigeminohypothalamic and spinohypothalamic tract neurons displaying substance P receptor-like immunoreactivity in the rat. J Comp Neurol 378: 508-521. doi:10.1002/(SICI)1096-9861(19970224)378:4. PubMed: 9034907.
[21]  Malick A, Burstein R (1998) Cells of origin of the trigeminohypothalamic tract in the rat. J Comp Neurol 400: 125-144. doi:10.1002/(SICI)1096-9861(19981012)400:1. PubMed: 9762871.
[22]  Malick A, Strassman RM, Burstein R (2000) Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. J Neurophysiol 84: 2078-2112. PubMed: 11024099.
[23]  Akerman S, Holland PR, Goadsby PJ (2011) Diencephalic and brainstem mechanisms in migraine. Nat Rev Neurosci 12: 570-584. doi:10.1038/nrn3057. PubMed: 21931334.
[24]  Charbit AR, Akerman S, Holland PR, Goadsby PJ (2009) Neurons of the dopaminergic/calcitonin gene-related peptide A11 cell group modulate neuronal firing in the trigeminocervical complex: an electrophysiological and immunohistochemical study. J Neurosci 29: 12532-12541. doi:10.1523/JNEUROSCI.2887-09.2009. PubMed: 19812328.
[25]  Zimmermann M (1983) Ethical guidelines for investigations of experimental pain in conscious animals. Pain 16: 109-110. doi:10.1016/0304-3959(83)90201-4. PubMed: 6877845.
[26]  Paxinos G, Watson CW (2007) The rat brain in stereotaxic coordinates. 6th Edition. San Diego: Academic Press.
[27]  Biag J, Huang Y, Gou L, Hintiryan H, Askarinam A et al. (2012) Cyto- and chemoarchitecture of the hypothalamic paraventricular nucleus in the C57BL/6J male mouse: a study of immunostaining and multiple fluorescent tract tracing. J Comp Neurol 520: 6-33. doi:10.1002/cne.22698. PubMed: 21674499.
[28]  Swanson LW, Kuypers HG (1980b) The paraventricular nucleus of the hypothalamus: cytoarchitectonic subdivisions and organization of projections to the pituitary, dorsal vagal complex, and spinal cord as demonstrated by retrograde fluorescence double-labeling methods. J Comp Neurol 194: 555-570. doi:10.1002/cne.901940306. PubMed: 7451682.
[29]  Cechetto DF, Saper CB (1988) Neurochemical organization of the hypothalamic projection to the spinal cord in the rat. J Comp Neurol 272: 579-604. doi:10.1002/cne.902720410. PubMed: 2901438.
[30]  Nylén A, Skagerberg G, Alm P, Larsson B, Holmqvist B et al. (2001) Nitric oxide synthase in the hypothalamic paraventricular nucleus of the female rat; organization of spinal projections and coexistence with oxytocin or vasopressin. Brain Res 908: 10-24. doi:10.1016/S0006-8993(01)02539-2. PubMed: 11457427.
[31]  Strassman AM, Vos BP (1993) Somatotopic and laminar organization of fos-like immunoreactivity in the medullary and upper cervical dorsal horn induced by noxious facial stimulation in the rat. J Comp Neurol 331: 495-516. doi:10.1002/cne.903310406. PubMed: 8509507.
[32]  Molander C, Xu Q, Rivero-Melian C, Grant G (1989) Cytoarchitectonic organization of the spinal cord in the rat: II. The cervical and upper thoracic cord. J Comp Neurol 289: 375-385. doi:10.1002/cne.902890303. PubMed: 2808773.
[33]  Yoshida A, Dostrovsky JO, Sessle BJ, Chiang CY (1991) Trigeminal projections to the nucleus submedius of the thalamus in the rat. J Comp Neurol 307: 609-625. doi:10.1002/cne.903070408. PubMed: 1714465.
[34]  Skagerberg G, Lindvall O (1985) Organization of diencephalic dopamine neurones projecting to the spinal cord in the rat. Brain Res 342: 340-351. doi:10.1016/0006-8993(85)91134-5. PubMed: 4041835.
[35]  Swanson LW, Sanchez-Watts G, Watts AG (2005) Comparison of melanin-concentrating hormone and hypocretin/orexin mRNA expression patterns in a new parceling scheme of the lateral hypothalamic zone. Neurosci Lett 387: 80-84. doi:10.1016/j.neulet.2005.06.066. PubMed: 16084021.
[36]  Swanson LW, Sawchenko PE (1983) Hypothalamic integration: organization of the paraventricular and supraoptic nuclei. Annu Rev Neurosci 6: 269-324. doi:10.1146/ PubMed: 6132586.
[37]  Swanson LW, McKellar S (1979) The distribution of oxytocin- and neurophysin-stained fibers in the spinal cord of the rat and monkey. J Comp Neurol 188: 87-106. doi:10.1002/cne.901880108. PubMed: 115910.
[38]  Saper CB, Loewy AD, Swanson LW, Cowan WM (1976) Direct hypothalamo-autonomic connections. Brain Res 117: 305-312. doi:10.1016/0006-8993(76)90738-1. PubMed: 62600.
[39]  Schmued LC, Heimer L (1990) Iontophoretic injection of fluoro-gold and other fluorescent tracers. J Histochem Cytochem 38: 721-723. doi:10.1177/38.5.2332627. PubMed: 2332627.
[40]  Dado RJ, Burstein R, Cliffer KD, Giesler GJ Jr (1990) Evidence that Fluoro-Gold can be transported avidly through fibers of passage. Brain Res 533: 329-333. doi:10.1016/0006-8993(90)91358-N. PubMed: 1705157.
[41]  K?bbert C, Apps R, Bechmann I, Lanciego JL, Mey J et al. (2000) Current concepts in neuroanatomical tracing. Prog Neurobiol 62: 327-351. doi:10.1016/S0301-0082(00)00019-8. PubMed: 10856608.
[42]  Hosoya Y (1980) The distribution of spinal projection neurons in the hypothalamus of the rat, studied with the HRP method. Exp Brain Res 40: 79-87. PubMed: 7418761.
[43]  Swanson LW, Kuypers HG (1980) A direct projection from the ventromedial nucleus and retrochiasmatic area of the hypothalamus to the medulla and spinal cord of the rat. Neurosci Lett 17: 307-312. doi:10.1016/0304-3940(80)90041-5. PubMed: 7052476.
[44]  Sawchenko PE, Swanson LW (1982) Immunohistochemical identification of neurons in the paraventricular nucleus of the hypothalamus that project to the medulla or to the spinal cord in the rat. J Comp Neurol 205: 260-272. doi:10.1002/cne.902050306. PubMed: 6122696.
[45]  Hosoya Y, Matsushita M (1979) Identification and distribution of the spinal and hypophyseal projection neurons in the paraventricular nucleus of the rat. A light and electron microscopic study with the horseradish peroxidase method. Exp Brain Res 35: 315-331. PubMed: 86456.
[46]  Shafton AD, Ryan A, Badoer E (1998) Neurons in the hypothalamic paraventricular nucleus send collaterals to the spinal cord and to the rostral ventrolateral medulla in the rat. Brain Res 801: 239-243. doi:10.1016/S0006-8993(98)00587-3. PubMed: 9729407.
[47]  Wagner CK, Sisk CL, Clemens LG (1993) Neurons in the paraventricular nucleus of the hypothalamus that project to the sexually dimorphic lower lumbar spinal cord concentrate 3H-estradiol in the male rat. J Neuroendocrinol 5: 545-551. doi:10.1111/j.1365-2826.1993.tb00520.x. PubMed: 8680423.
[48]  Nilaver G, Zimmerman EA, Wilkins J, Michaels J, Hoffman D et al. (1980) Magnocellular hypothalamic projections to the lower brain stem and spinal cord of the rat. Immunocytochemical evidence for predominance of the oxytocin-neurophysin system compared to the vasopressin-neurophysin system. Neuroendocrinology 30: 150-158. doi:10.1159/000122991. PubMed: 6154267.
[49]  Portillo F, Carrasco M, Vallo JJ (1998) Separate populations of neurons within the paraventricular hypothalamic nucleus of the rat project to vagal and thoracic autonomic preganglionic levels and express c-Fos protein induced by lithium chloride. J Chem Neuroanat 14: 95-102. doi:10.1016/S0891-0618(97)10022-9. PubMed: 9625354.
[50]  Hosoya Y, Matsushita M (1981) Brainstem projections from the lateral hypothalamic area in the rat, as studied with autoradiography. Neurosci Lett 24: 111-116. doi:10.1016/0304-3940(81)90232-9. PubMed: 6166908.
[51]  Ondo WG, He Y, Rajasekaran S, Le WD (2000) Clinical correlates of 6-hydroxydopamine injections into A11 dopaminergic neurons in rats: a possible model for restless legs syndrome. Mov Disord 15: 154-158. doi:10.1002/1531-8257(200001)15:1. PubMed: 10634257.
[52]  Skagerberg G, Bjorklund A, Lindvall O, Schmidt RH (1982) Origin and termination of the diencephalo-spinal dopamine system in the rat. Brain. Res Bull 9: 237-244. doi:10.1016/0361-9230(82)90136-8.
[53]  Holstege JC, Van Dijken H, Buijs RM, Goedknegt H, Gosens T et al. (1996) Distribution of dopamine immunoreactivity in the rat, cat and monkey spinal cord. J Comp Neurol 376: 631-652. doi:10.1002/(SICI)1096-9861(19961223)376:4. PubMed: 8978475.
[54]  Qu S, Ondo WG, Zhang X, Xie WJ, Pan TH et al. (2006) Projections of diencephalic dopamine neurons into the spinal cord in mice. Exp Brain Res 168: 152-156. doi:10.1007/s00221-005-0075-1. PubMed: 16044299.
[55]  Pappas SS, Tiernan CT, Behrouz B, Jordan CL, Breedlove SM et al. (2010) Neonatal androgen-dependent sex differences in lumbar spinal cord dopamine concentrations and the number of A11 diencephalospinal dopamine neurons. J Comp Neurol 518: 2423-2436. PubMed: 20503420.
[56]  Barraud Q, Obeid I, Aubert I, Barrière G, Contamin H et al. (2010) Neuroanatomical study of the A11 diencephalospinal pathway in the non-human primate. PLOS ONE 5: e13306. doi:10.1371/journal.pone.0013306. PubMed: 20967255.
[57]  Pasquier DA, Tramezzani JH (1979) Afferent connections of the hypothalamic retrochiasmatic area in the rat. Brain. Res Bull 4(6): 765-771. doi:10.1016/0361-9230(79)90010-8.
[58]  Berk ML, Finkelstein JA (1981) An autoradiographic determination of the efferent projections of the suprachiasmatic nucleus of the hypothalamus. Brain Res 226: 1-13. doi:10.1016/0006-8993(81)91079-9. PubMed: 7296282.
[59]  Stephan FK, Berkley KJ, Moss RL (1981) Efferent connections of the rat suprachiasmatic nucleus. Neuroscience 6: 2625-2641. doi:10.1016/0306-4522(81)90108-1. PubMed: 7322354.
[60]  Watts AG, Swanson LW (1987) Efferent projections of the suprachiasmatic nucleus: II. Studies using retrograde transport of fluorescent dyes and simultaneous peptide immunohistochemistry in the rat. J Comp Neurol 258: 230-252. doi:10.1002/cne.902580205. PubMed: 2438309.
[61]  Johnson RF, Morin LP, Moore RY (1988) Retinohypothalamic projections in the hamster and rat demonstrated using cholera toxin. Brain Res 462: 301-312. doi:10.1016/0006-8993(88)90558-6. PubMed: 3191391.
[62]  Levine JD, Weiss ML, Rosenwasser AM, Miselis RR (1991) Retinohypothalamic tract in the female albino rat: a study using horseradish peroxidase conjugated to cholera toxin. J Comp Neurol 306: 344-360. doi:10.1002/cne.903060210. PubMed: 1711060.
[63]  Morin LP, Goodless-Sanchez N, Smale L, Moore RY (1994) Projections of the suprachiasmatic nuclei, subparaventricular zone and retrochiasmatic area in the golden hamster. Neuroscience 61: 391-410. doi:10.1016/0306-4522(94)90240-2. PubMed: 7526267.
[64]  Card JP, Moore RY (1989) Organization of lateral geniculate-hypothalamic connections in the rat. J Comp Neurol 284: 135-147. doi:10.1002/cne.902840110. PubMed: 2754028.
[65]  Elias CF, Saper CB, Maratos-Flier E, Tritos NA, Lee C et al. (1998) Chemically defined projections linking the mediobasal hypothalamus and the lateral hypothalamic area. J Comp Neurol 402: 442-459. doi:10.1002/(SICI)1096-9861(19981228)402:4. PubMed: 9862320.
[66]  Meng ID, Hu JW, Benetti AP, Bereiter DA (1997) Encoding of corneal input in two distinct regions of the spinal trigeminal nucleus in the rat: cutaneous receptive field properties, responses to thermal and chemical stimulation, modulation by diffuse noxious inhibitory controls, and projections to the parabrachial area. J Neurophysiol 77: 43-56. PubMed: 9120584.
[67]  Broton JG, Hu JW, Sessle BJ (1988) Effects of temporomandibular joint stimulation on nociceptive and nonnociceptive neurons of the cat’s trigeminal subnucleus caudalis (medullary dorsal horn). J Neurophysiol 59: 1575-1589. PubMed: 3385474.
[68]  Hu JW (1990) Response properties of nociceptive and non-nociceptive neurons in the rat’s trigeminal subnucleus caudalis (medullary dorsal horn) related to cutaneous and deep craniofacial afferent stimulation and modulation by diffuse noxious inhibitory controls. Pain 41: 331-345. doi:10.1016/0304-3959(90)90010-B. PubMed: 2388770.
[69]  Raboisson P, Dallel R, Clavelou P, Sessle BJ, Woda A (1995) Effects of subcutaneous formalin on the activity of trigeminal brain stem nociceptive neurones in the rat. J Neurophysiol 73: 496-505. PubMed: 7760113.
[70]  Burstein R, Yamamura H, Malick A, Strassman AM (1998) Chemical stimulation of the intracranial dura induces enhanced responses to facial stimulation in brain stem trigeminal neurons. J Neurophysiol 79: 964-982. PubMed: 9463456.
[71]  Truesdell LS, Bodnar RJ (1987) Reduction in cold-water swim analgesia following hypothalamic paraventricular nucleus lesions. Physiol Behav 39: 727-731. doi:10.1016/0031-9384(87)90257-5. PubMed: 3602125.
[72]  Wang QA, Mao LM, Han JS (1990) Analgesia from electrical stimulation of the hypothalamic arcuate nucleus in pentobarbital-anesthetized rats. Brain Res 526: 221-227. doi:10.1016/0006-8993(90)91225-6. PubMed: 2257483.
[73]  Yirmiya R, Ben-Eliyahu S, Shavit Y, Marek P, Liebeskind JC (1990) Stimulation of the hypothalamic paraventricular nucleus produces analgesia not mediated by vasopressin or endogenous opioids. Brain Res 537: 169-174. doi:10.1016/0006-8993(90)90354-E. PubMed: 1982239.
[74]  Miranda-Cardenas Y, Rojas-Piloni G, Martínez-Lorenzana G, Rodríguez-Jiménez J, López-Hidalgo M et al. (2006) Oxytocin and electrical stimulation of the paraventricular hypothalamic nucleus produce antinociceptive effects that are reversed by an oxytocin antagonist. Pain 122: 182-189. doi:10.1016/j.pain.2006.01.029. PubMed: 16527400.
[75]  Yang J, Chen JM, Song CY, Liu WY, Wang G et al. (2006) Through the central V2, not V1 receptors influencing the endogenous opiate peptide system, arginine vasopressin, not oxytocin in the hypothalamic paraventricular nucleus involves in the antinociception in the rat. Brain Res 1069: 127-138. doi:10.1016/j.brainres.2005.11.045. PubMed: 16409991.
[76]  Pinto-Ribeiro F, Ansah OB, Almeida A, Pertovaara A (2008) Influence of arthritis on descending modulation of nociception from the paraventricular nucleus of the hypothalamus. Brain Res 1197: 63-75. doi:10.1016/j.brainres.2007.12.038. PubMed: 18242585.
[77]  Matsumoto N, Kawarada K, Kamata K, Suzuki TA (1993) Electrical stimulation of tooth pulp increases the expression of c-fos in the cat supraoptic nucleus but not in the paraventricular nucleus. Life Sci 53: 1235-1241. doi:10.1016/0024-3205(93)90542-B. PubMed: 8412481.
[78]  Berkowitz BA, Sherman S (1982) Characterization of vasopressin analgesia. J Pharmacol Exp Ther 220: 329-334. PubMed: 7057394.
[79]  Breton JD, Veinante P, Uhl-Bronner S, Vergnano AM, Freund-Mercier MJ et al. (2008) Oxytocin-induced antinociception in the spinal cord is mediated by a subpopulation of glutamatergic neurons in lamina I-II which amplify GABAergic inhibition. Mol Pain 4: 19. doi:10.1186/1744-8069-4-19. PubMed: 18510735.
[80]  Mogil JS, Sorge RE, LaCroix-Fralish ML, Smith SB, Fortin A et al. (2011) Pain sensitivity and vasopressin analgesia are mediated by a gene-sex-environment interaction. Nat Neurosci 14: 1569-1573. doi:10.1038/nn.2941. PubMed: 22019732.
[81]  Zubrzycka M, Janecka A (2005) Effects of centrally administered vasopressin on orofacial pain perception in rats. Brain Res 1051: 112-116. doi:10.1016/j.brainres.2005.05.058. PubMed: 15993385.
[82]  Zubrzycka M, Janecka A (2008) Interactions of galanin with endomorphin-2, vasopressin and oxytocin in nociceptive modulation of the trigemino-hypoglossal reflex in rats. Physiol Res 57: 769-776. PubMed: 17949254.
[83]  Mazzuca M, Minlebaev M, Shakirzyanova A, Tyzio R, Taccola G et al. (2011) Newborn analgesia mediated by oxytocin during delivery. Front Cell Neurosci 5: 3. PubMed: 21519396.
[84]  Gura EV (2000) Vasopressin-mediated modulation of trigeminal reflexes in rats. Neurophysiology 32: 371-375. doi:10.1023/A:1010487932269.
[85]  Franco AC, Prado WA (1996) Antinociceptive effects of stimulation of discrete sites in the rat hypothalamus: evidence for the participation of the lateral hypothalamus area in descending pain suppression mechanisms. Braz J Med Biol Res 29: 1531-1541. PubMed: 9196558.
[86]  Dafny N, Dong WQ, Prieto-Gomez C, Reyes-Vazquez C, Stanford J et al. (1996) Lateral hypothalamus: site involved in pain modulation. Neuroscience 70: 449-460. doi:10.1016/0306-4522(95)00358-4. PubMed: 8848153.
[87]  Peyron C, Tighe DK, van den Pol AN, De Lecea L, Heller HC et al. (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18: 9996-10015. PubMed: 9822755.
[88]  van den Pol AN (1999) Hypothalamic hypocretin (orexin): robust innervation of the spinal cord. J Neurosci 19: 3171-3182. PubMed: 10191330.
[89]  Sakurai T, Mieda M (2011) Connectomics of orexin-producing neurons: interface of systems of emotion, energy homeostasis and arousal. Trends Pharmacol Sci 32: 451-462. doi:10.1016/ PubMed: 21565412.
[90]  Chiou LC, Lee HJ, Ho YC, Chen SP, Liao YY et al. (2010) Orexins/hypocretins: pain regulation and cellular actions. Curr Pharm Des 16: 3089-3100. doi:10.2174/138161210793292483. PubMed: 20687883.
[91]  Holland PR, Akerman S, Goadsby PJ (2006) Modulation of nociceptive dural input to the trigeminal nucleus caudalis via activation of the orexin 1 receptor in the rat. Eur J Neurosci 24: 2825-2833. doi:10.1111/j.1460-9568.2006.05168.x. PubMed: 17156207.
[92]  Rainero I, Rubino E, Gallone S, Fenoglio P, Picci LR et al. (2011) Evidence for an association between migraine and the hypocretin receptor 1 gene. J Headache Pain 12: 193-199. doi:10.1007/s10194-011-0314-8. PubMed: 21344296.
[93]  Fleetwood-Walker SM, Hope PJ, Mitchell R (1988) Antinociceptive actions of descending dopaminergic tracts on cat and rat dorsal horn somatosensory neurones. J Physiol 399: 335-348. PubMed: 2841456.
[94]  Wei H, Viisanen H, Pertovaara A (2009) Descending modulation of neuropathic hypersensitivity by dopamine D2 receptors in or adjacent to the hypothalamic A11 cell group. Pharmacol Res 59: 355-363. doi:10.1016/j.phrs.2009.01.001. PubMed: 19416636.
[95]  Taniguchi W, Nakatsuka T, Miyazaki N, Yamada H, Takeda D et al. (2011) In vivo patch-clamp analysis of dopaminergic antinociceptive actions on substantia gelatinosa neurons in the spinal cord. Pain 152: 95-105. doi:10.1016/j.pain.2010.09.034. PubMed: 21050660.
[96]  Lapirot O, Melin C, Modolo A, Nicolas C, Messaoudi Y et al. (2011) Tonic and phasic descending dopaminergic controls of nociceptive transmission in the medullary dorsal horn. Pain 152: 1821-1831. doi:10.1016/j.pain.2011.03.030. PubMed: 21514054.
[97]  Bellasio S, Nicolussi E, Bertorelli R, Reggiani A (2003) Melanocortin receptor agonists and antagonists modulate nociceptive sensitivity in the mouse formalin test. Eur J Pharmacol 482: 127-132. doi:10.1016/j.ejphar.2003.09.017. PubMed: 14660013.
[98]  Peterlin BL, Rapoport AM, Kurth T (2010) Migraine and obesity: epidemiology, mechanisms, and implications. Headache 50: 631-648. doi:10.1111/j.1526-4610.2009.01554.x. PubMed: 19845784.


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