Аннотация
Нарушениям в серотонинергической системе головного мозга отводят ведущую роль в патогенезе хронической абдоминальной боли и коморбидных ей соматических гипералгезий, которые беспокоят значительную часть пациентов с заболеваниями пищеварительного тракта, даже в состоянии ремиссии. Однако конкретные изменения в ноцицептивных свойствах серотонинергических структур, которые могут быть инициированы органической патологией и сохраняться после ее разрешения, остаются неясными. Целью проведенных нами нейрофизиологических экспериментов на анестезированных крысах, здоровых и перенесших колит, являлось выявление сохраняющихся после разрешения кишечного воспаления перестроек в нейрональных реакциях большого (БЯШ) и дорсального (ДЯШ) ядер шва на висцеральное (колоректальное растяжение) и соматическое (сдавливание хвоста) болевые раздражения. Установлено, что оба ядра содержат разные группы ноцицептивных нейронов: 1) отвечающие активацией только на колоректальное растяжение (висцеральные); 2) возбуждающиеся только при сдавливании хвоста (соматические); 3) реагирующие возбуждением на оба раздражения (общие); 4) отвечающие на любую из стимуляций торможением разрядов (тормозящиеся). По сравнению со здоровыми животными, в БЯШ крыс, перенесших колит, было повышено количество тормозящихся клеток и снижена общая доля возбуждающихся ноцицептивных нейронов. Растяжение перенесшей воспаление кишки вызывало в БЯШ усиленное нейрональное торможение, тогда как сдавливание незатронутого патологией хвоста приводило к повышенному возбуждению его селективных соматических и общих ноцицептивных клеток. В свою очередь, в ДЯШ постколитных крыс доля тормозящихся нейронов была снижена, а в возросшей популяции возбуждающихся было меньше висцеральных и больше соматических ноцицептивных клеток. Это сопровождалось усилением избирательных реакций последних на соматические болевые стимулы и возрастанием неселективного возбуждения нейронов ДЯШ в ответ на висцеральные и соматические болевые сигналы. Выявленные нейрональные перестройки могут способствовать постколитному нарушению функций изученных ядер шва в эндогенном контроле висцеральной и соматической болевых чувствительностей.
Литература
Гаус ОВ, Ливзан МА (2020) Фундаментальные основы формирования абдоминальной боли у пациентов с синдромом раздраженного кишечника. Эффект фармакотер 16(15): 102–111. [Gaus OV, Livzan MA (2020) Fundamentals of abdominal pain formation in IBS patients. Effect pharmacoth 16(15): 102–111. (In Russ)]. https://doi.org/10.33978/2307-3586-2020-16-15-102-111.
Агафонова НА, Яковенко ЭП, Иванов АН, Яковенко АВ (2018) Aбдоминальная боль и висцеральная гиперчувствительность – две грани одной реальности для пациентов с СРК. Эффект фармакотер 32: 26–33. [Agafonova NA, Yakovenko EP, Ivanov AN, Yakovenko AV (2018) Abdominal pain and visceral hypersensitivity like two sides of the same reality for IBS patients. Effect pharmacother 32: 26–33. (In Russ)].
Bielefeldt K, Davis B, Binion DG. (2009) Pain and inflammatory bowel disease. Inflamm Bowel Dis 15(5):778–788. https://doi.org/10.1002/ibd.20848.
Vergnolle N (2022) Abdominal pain in irritable bowel syndrome. Nat. Rev. Gastroenterol Hepatol. 19:350. https://doi.org/10.1038/s41575-022-00599-6.
Wils P, Caron B, D'Amico F, Danese S, Peyrin-Biroulet L. (2022) Abdominal Pain in Inflammatory Bowel Diseases: A Clinical Challenge. J Clin Med 11(15):4269. https://doi.org/10.3390/jcm11154269.
Ceuleers H, Van Spaendonk H, Hanning N, Heirbaut J, Lambeir AM, Joossens J, Augustyns K, De Man JG, De Meester I, De Winter BY. (2016) Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases. World J Gastroenterol 22(47):10275–10286. https://doi.org/10.3748/wjg.v22.i47.
Farzaei MH, Bahramsoltani R, Abdollahi M, Rahimi R (2016) The Role of Visceral Hypersensitivity in Irritable Bowel Syndrome: Pharmacological Targets and Novel Treatments. J Neurogastroenterol Motil 22(4):558–574. https://doi.org/10.5056/jnm16001.
Crowell MD (2004) Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol 141(8):1285–1293. https://doi.org/10.1038/sj.bjp.0705762.
Gros M, Gros B, Mesonero JE, Latorre E (2021) Neurotransmitter Dysfunction in Irritable Bowel Syndrome: Emerging Approaches for Management. J Clin Med 10(15):3429. https://doi.org/10.3390/jcm10153429.
Takahashi K, Khwaja IG, Schreyer JR, Bulmer D, Peiris M, Terai S, Aziz Q (2021) Post-inflammatory Abdominal Pain in Patients with Inflammatory Bowel Disease During Remission: A Comprehensive Review. Crohn's & Colitis 360 3:4:otab073. https://doi.org/10.1093/crocol/otab073.
Nakai A, Kumakura Y, Boivin M, Rosa P, Diksic M, D'Souza D, Kersey K (2003) Sex differences of brain serotonin synthesis in patients with irritable bowel syndrome using alpha-[11C]methyl-L-tryptophan, positron emission tomography and statistical parametric mapping. Can J Gastroenterol 17(3):191–196. https://doi.org/10.1155/2003/572127.
O'Mahony S, Chua AS, Quigley EM, Clarke G, Shanahan F, Keeling PW, Dinan TG (2008) Evidence of an enhanced central 5HT response in irritable bowel syndrome and in the rat maternal separation model. Neurogastroenterol Motil 20(6):680–688. https://doi.org/10.1111/j.1365-2982.2007.01065.x.
Ren TH, Wu J, Yew D, Ziea E, Lao L, Leung WK, Berman B, Hu PJ, Sung JJ (2007) Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 292(3):G849–G856. https://doi.org/10.1152/ajpgi.00400.2006.
Zhang HA, Sang N, Ge X, Huang Q, Li XL, Sha J (2018) Nesfatin-1 in the dorsal raphe nucleus influences visceral sensitivity via 5-HT neurons in male maternally separated rats. Sci Rep 8:9334. https://doi.org/10.1038/s41598-018-27592-x.
Goehler LE, Gaykema RP, Opitz N, Reddaway R, Badr N, Lyte M (2005) Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav. Immun 19(4):334–344. https://doi.org/10.1016/j.bbi.2004.09.002.
Lu Y, Westlund KN (2001) Effects of baclofen on colon inflammation-induced Fos, CGRP and SP expression in spinal cord and brainstem. Brain Res 889:118–130. https://doi.org/10.1016/s0006-8993(00)03124-3.
Wan J, Ding Y, Tahir AH, Shah MK, Janyaro H, Li X, Zhong J, Vodyanoy V, Ding M (2017) Electroacupuncture attenuates visceral hypersensitivity by inhibiting JAK2/STAT3 signaling pathway in the descending pain modulation system. Front Neurosci 11:644. https://doi.org/10.3389/fnins.2017.00644.
Sanoja R., Tortorici V, Fernandez C, Price TJ, Cervero F (2010) Role of RVM neurons in capsaicin-evoked visceral nociception and referred hyperalgesia. Eur J Pain 14(2):120.e1–e9. https://doi.org/10.1016/j.ejpain.2009.04.006.
Chen MX, Chen Y, Fu R, Liu SY, Yang QQ, Shen TB (2016) Activation of 5-HT and NR2B contributes to visceral hypersensitivity in irritable bowel syndrome in rats. Am J Transl Res 8(12):5580–5590. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5209508/.
Martins I, Tavares I (2017) Reticular Formation and Pain: The Past and the Future. Front Neuroanat 11:51. https://doi.org/10.3389/fnana.2017.00051.
Ossipov MH, Dussor GO, Porreca F (2010) Central modulation of pain. J Clin Invest 120(11):3779–3787. https://doi.org/10.1172/JCI43766.
Wang Q-P, Nakai Y (1994) The dorsal raphe: An important nucleus in pain modulation. Brain Res Bull 34(6):575–585. https://doi.org/10.1016/0361-9230(94)90143-0.
Millan MJ (2002) Descending control of pain. Prog Neurobiol 66(6):355–474. https://doi.org/10.1016/s0301-0082(02)00009-6.
Wei F, Gu M, Chu YX (2012) New tricks for an old slug: descending serotonergic system in pain. Sheng Li Xue Bao 64(5):520–530.
Mercer Lindsay N, Chen C, Gilam G, Mackey S, Scherrer G (2021) Brain circuits for pain and its treatment. Sci Transl Med 13(619):eabj7360. https://doi.org/10.1126/scitranslmed.abj7360.
Almeida TF, Roizenblatt S, Tufik S (2004) Afferent pain pathways: a neuroanatomical review. Brain Res 1000(1–2):40–56. https://doi.org/10.1016/j.brainres.2003.10.073.
Almeida A, Leite-Almeida H, Tavares I (2006) Medullary control of nociceptive transmission: Reciprocal dual communication with the spinal cord. Drug Discov Today Dis Mech 3(3):305–312. https://doi.org/10.1016/j.ddmec.2006.09.001.
Chen Q, Heinricher MM (2022) Shifting the Balance: How Top-Down and Bottom-Up Input Modulate Pain via the Rostral Ventromedial Medulla. Front Pain Res (Lausanne) 3:932476. https://doi.org/10.3389/fpain.2022.932476.
Cleary DR, Heinricher MM (2013) Adaptations in responsiveness of brainstem pain-modulating neurons in acute compared with chronic inflammation. Pain 154(6):845–855. https://doi.org/10.1016/j.pain.2013.02.019.
Porreca F, Ossipov MH, Gebhart GF (2002) Chronic pain and medullary descending facilitation. Trends Neurosci 25(6):319–325. https://doi.org/10.1016/s0166-2236(02)02157-4.
Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL (1989) Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96(3):795–803.
Lyubashina OA, Sivachenko IB, Busygina II, Panteleev SS (2018) Colitis-induced alterations in response properties of visceral nociceptive neurons in the rat caudal medulla oblongata and their modulation by 5-HT3 receptor blockade. Brain Res Bull 142:183–196. https://doi.org/10.1016/j.brainresbull.2018.07.013.
Lyubashina OA, Sivachenko IB, Busygina II (2021) Amygdalofugal Modulation of Visceral Nociceptive Transmission in the Rat Caudal Ventrolateral Medulla under Normal Conditions and Intestinal Inflammation. J Evol Biochem Physiol 57:5:1150–1162. https://doi.org/10.1134/S0022093021050161.
Lyubashina OA, Sivachenko IB, Mikhalkin AA (2022) Impaired visceral pain-related functions of the mid-brain periaqueductal gray in rats with colitis. Brain Res Bull 182:12-25. https://doi.org/10.1016/j.brainresbull.2022.02.002.
Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates. 4th ed London Acad Press.
Fields HL, Bry J, Hentall I, Zorman G (1983) The activity of neurons in the rostral medulla of the rat during withdrawal from noxious heat. J Neurosci 3(12):2545–2552. https://doi.org/10.1523/JNEUROSCI.03-12-02545.1983.
Heinricher MM (2016) Pain Modulation and the Transition from Acute to Chronic Pain. Adv Exp Med Biol 904:105–115. https://doi.org/10.1007/978-94-017-7537-3_8.
Heinricher MM, Morgan MM, Fields HL (1992) Direct and indirect actions of morphine on medullary neurons that modulate nociception. Neuroscience 48(3):533–543. https://doi.org/10.1016/0306-4522(92)90400-v.
Brink TS, Hellman KM, Lambert AM, Mason P (2006) Raphe magnus neurons help protect reactions to visceral pain from interruption by cutaneous pain. J Neurophysiol 96(6):3423–3432. https://doi.org/10.1152/jn.00793.2006.
Brink TS, Mason P (2003) Raphe magnus neurons respond to noxious colorectal distension. J Neurophysiol 89(5):2506–2515. https://doi.org/10.1152/jn.00825.2002.
Sikandar S, Dickenson AH (2011) Pregabalin modulation of spinal and brainstem visceral nociceptive processing. Pain 152(10):2312–2322. https://doi.org/10.1016/j.pain.2011.06.020.
Chen T, Dong YX, Li YQ (2003) Fos expression in serotonergic neurons in the rat brainstem following noxious stimuli: an immunohistochemical double-labelling study. J Anat 203(6):579–588. https://doi.org/10.1046/j.1469-7580.2003.00242.x.
Dong YX, Han ZA, Xiong KH, Rao ZR (1997) Fos expression in serotonergic midbrain neurons projecting to the paraventricular nucleus of hypothalamus after noxious stimulation of the stomach: a triple labeling study in the rat. Neurosci Res 27(2):155–160. https://doi.org/10.1016/s0168-0102(96)01143-1.
Vilela FC, Vieira JS, Vitor-Vieira F, Kalil-Cutti B, da Silva JRT, Giusti-Paiva A, da Silva ML (2021) Maternal separation increases pain sensitivity by reducing the activity of serotonergic neurons in the dorsal raphe nucleus and noradrenergic neurons in locus coeruleus. Neurosci Lett 748:135734. https://doi.org/10.1016/j.neulet.2021.135734.
Montagne-Clavel J, Oliveras JL, Martin G (1995) Single-unit recordings at dorsal raphe nucleus in the awake-anesthetized rat: spontaneous activity and responses to cutaneous innocuous and noxious stimulations. Pain 60(3):303–310. https://doi.org/10.1016/0304-3959(94)00129-3.
Shima K, Nakahama H, Yamamoto M (1986) Firing properties of two types of nucleus raphe dorsalis neurons during the sleep-waking cycle and their responses to sensory stimuli. Brain Res 399(2):317–326. https://doi.org/10.1016/0006-8993(86)91522-2.
Lyubashina OA, Sivachenko IB, Sokolov AY (2019) Differential responses of neurons in the rat caudal ventrolateral medulla to visceral and somatic noxious stimuli and their alterations in colitis. Brain Res Bull 152:299–310. https://doi.org/10.1016/j.brainresbull.2019.07.030.
Ness TJ, Follett KA, Piper J, Dirks BA (1998) Characterization of neurons in the area of the medullary lateral reticular nucleus responsive to noxious visceral and cutaneous stimuli. Brain Res 802(1–2):163–174. https://doi.org/10.1016/s0006-8993(98)00608-8.
Pinto-Ribeiro F, Ansah OB, Almeida A, Pertovaara A (2011) Response properties of nociceptive neurons in the caudal ventrolateral medulla (CVLM) in monoarthritic and healthy control rats: modulation of responses by the paraventricular nucleus of the hypothalamus (PVN). Brain Res Bull 86(1–2):82–90. https://doi.org/10.1016/j.brainresbull.2011.06.014.
Luz LL, Fernandes EC, Sivado M, Kokai E, Szucs P, Safronov BV (2015) Monosynaptic convergence of somatic and visceral C-fiber afferents on projection and local circuit neurons in lamina I: a substrate for referred pain. Pain 156(10):2042–2051. https://doi.org/10.1097/j.pain.0000000000000267.
Qin C, Farber JP, Linderoth B, Shahid A, Foreman RD (2008) Neuromodulation of thoracic intraspinal visceroreceptive transmission by electrical stimulation of spinal dorsal column and somatic afferents in rats. J Pain 9(1):71– 78. https://doi.org/10.1016/j.jpain.2007.08.007.
Snowball RK, Semenenko FM, Lumb BM (2000) Visceral inputs to neurons in the anterior hypothalamus including those that project to the periaqueductal gray: a functional anatomical and electrophysiological study. Neuroscience 99(2):351–361. https://doi.org/10.1016/s0306-4522(00)00203-7.
Monconduit L, Bourgeais L, Bernard JF, Villanueva L (2003) Convergence of cutaneous, muscular and visceral noxious inputs onto ventromedial thalamic neurons in the rat. Pain 103(1–2):83–91. https://doi.org/10.1016/s0304-3959(02)00418-9.
Zhang HQ, Al-Chaer ED, Willis WD (2002) Effect of tactile inputs on thalamic responses to noxious colorectal distension in rat. J Neurophysiol 88(3):1185–1196. https://doi.org/10.1152/jn.2002.88.3.1185.
Zhang HQ, Rong PJ, Zhang SP, Al-Chaer ED, Willis WD (2003) Noxious visceral inputs enhance cutaneous tactile response in rat thalamus. Neurosci Lett 336(2):109–112. https://doi.org/10.1016/s0304-3940(02)01243-0.
Huang KW, Ochandarena NE, Philson AC, Hyun M, Birnbaum JE, Cicconet M, Sabatini BL (2019) Molecular and anatomical organization of the dorsal raphe nucleus. Elife 8:e46464. https://doi.org/10.7554/eLife.46464.
Nguyen E, Smith KM, Cramer N, Holland RA, Bleimeister IH, Flores-Felix K, Silberberg H, Keller A, Le Pichon CE, Ross SE (2022) Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit. Brain 145(7):2586–2601. https://doi.org/10.1093/brain/awac189.
Soiza-Reilly M, Commons KG (2014) Unraveling the architecture of the dorsal raphe synaptic neuropil using high-resolution neuroanatomy. Front Neural Circuits 8:105. https://doi.org/10.3389/fncir.2014.00105.
Zhao Q, Ito T, Soko C, Hori Y, Furuyama T, Hioki H, Konno K, Yamasaki M, Watanabe M, Ohtsuka S, Ono M, Kato N, Yamamoto R (2022) Histochemical Characterization of the Dorsal Raphe-Periaqueductal Grey Dopamine Transporter Neurons Projecting to the Extended Amygdala. eNeuro 9(3):ENEURO.0121-22.2022. https://doi.org/10.1523/ENEURO.0121-22.2022.
Gau R, Sévoz-Couche C, Hamon M, Bernard JF (2013) Noxious stimulation excites serotonergic neurons: a comparison between the lateral paragigantocellular reticular and the raphe magnus nuclei. Pain 154(5):647–659. https://doi.org/10.1016/j.pain.2012.09.012.
Gao K, Mason P (2000) Serotonergic Raphe magnus cells that respond to noxious tail heat are not ON or OFF cells. J Neurophysiol 84(4):1719–1725. https://doi.org/10.1152/jn.2000.84.4.1719.
Radhakrishnan R, Sluka KA (2009) Increased glutamate and decreased glycine release in the rostral ventromedial medulla during induction of a pre-clinical model of chronic widespread muscle pain. Neurosci Lett 457(3):141–145. https://doi.org/10.1016/j.neulet.2009.03.086.
Winkler CW, Hermes SM, Chavkin CI, Drake CT, Morrison SF, Aicher SA (2006) Kappa opioid receptor (KOR) and GAD67 immunoreactivity are found in OFF and NEUTRAL cells in the rostral ventromedial medulla. J Neurophysiol 96(6):3465–3473. https://doi.org/10.1152/jn.00676.2006.
Zhang Y, Zhao S, Rodriguez E, Takatoh J, Han BX, Zhou X, Wang F (2015) Identifying local and descending inputs for primary sensory neurons. J Clin Invest 125(10):3782–3794. https://doi.org/10.1172/JCI81156.
Pedersen NP, Vaughan CW, Christie MJ (2011) Opioid receptor modulation of GABAergic and serotonergic spinally projecting neurons of the rostral ventromedial medulla in mice. J Neurophysiol 106(2):731–740. https://doi.org/10.1152/jn.01062.2010.
Yang B, Zhang LC, Zeng YM (2003) [Microinjection of L-NAME into dorsal raphe nucleus inhibits nociceptive response in sigmoid pain model of rats. Sheng Li Xue Bao 55(5):577–582. (In Chinese)].
Lyubashina O, Busygina I, Sivachenko I, Panteleev S (2021) 5-HT1A Receptor Activation by Buspirone Facilitates Post-Inflammatory Intestinal Hypersensitivity in a Rat Model. FASEB J 35(S1):02269. https://doi.org/10.1096/fasebj.2021.35.S1.02269.
Deiteren A, van der Linden L, de Wit A, Ceuleers H, Buckinx R, Timmermans JP, Moreels TG, Pelckmans PA, De Man JG, De Winter BY (2015) P2X3 receptors mediate visceral hypersensitivity during acute chemically-induced colitis and in the post-inflammatory phase via different mechanisms of sensitization. PLoS One 10(4):e0123810. https://doi.org/10.1371/journal.pone.0123810.
Eijkelkamp N, Kavelaars A, Elsenbruch S, Schedlowski M, Holtmann G, Heijnen CJ (2007) Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior. Am J Physiol Gastrointest Liver Physiol 293(4):G749–G757. https://doi.org/10.1152/ajpgi.00114.2007.
Zhou Q, Price DD, Caudle RM, Verne GN (2008) Visceral and somatic hypersensitivity in TNBS-induced colitis in rats. Dig Dis Sci 53(2):429–435. https://doi.org/10.1007/s10620-007-9881-6.
Carlson JD, Maire JJ, Martenson ME, Heinricher MM (2007) Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. J Neurosci 27(48):13222–13231. https://doi.org/10.1523/JNEUROSCI.3715-07.2007.
Gonçalves L, Almeida A, Pertovaara A (2007) Pronociceptive changes in response properties of rostroventromedial medullary neurons in a rat model of peripheral neuropathy. Eur J Neurosci 26(8):2188–2195. https://doi.org/10.1111/j.1460-9568.2007.05832.x.
Kincaid W, Neubert MJ, Xu M, Kim CJ, Heinricher MM (2006) Role for medullary pain facilitating neurons in secondary thermal hyperalgesia. J Neurophysiol 95(1):33–41. https://doi.org/10.1152/jn.00449.2005.
Costa-Pereira JT, Serrão P, Martins I, Tavares I (2020) Serotoninergic pain modulation from the rostral ventromedial medulla (RVM) in chemotherapy-induced neuropathy: The role of spinal 5-HT3 receptors. Eur J Neurosci 51(8):1756–1769. https://doi.org/10.1111/ejn.14614.
Wei F, Dubner R, Zou S, Ren K, Bai G, Wei D, Guo W (2010) Molecular depletion of descending serotonin unmasks its novel facilitatory role in the development of persistent pain. J Neurosci 30:8624–8636. https://doi.org/10.1523/JNEUROSCI.5389-09.2010.
Zhang L, Hammond DL (2010) Cellular basis for opioid potentiation in the rostral ventromedial medulla of rats with persistent inflammatory nociception. Pain 149(1):107–116. https://doi.org/10.1016/j.pain.2010.01.017.
Aby F, Lorenzo LE, Grivet Z, Bouali-Benazzouz R, Martin H, Valerio S, Whitestone S, Isabel D, Idi W, Bouchatta O, De Deurwaerdere P, Godin AG, Herry C, Fioramonti X, Landry M, De Koninck Y, Fossat P (2022) Switch of serotonergic descending inhibition into facilitation by a spinal chloride imbalance in neuropathic pain. Sci Adv 8(30):eabo0689. https://doi.org/10.1126/sciadv.abo0689.
Cai Y-Q, Wang W, Hou Y-Y, Pan ZZ (2014) Optogenetic Activation of Brainstem Serotonergic Neurons Induces Persistent Pain Sensitization. Molecular Pain 10. https://doi.org/10.1186/1744-8069-10-70.
Suzuki R, Rygh LJ, Dickenson AH (2004) Bad news from the brain: descending 5-HT pathways that control spinal pain processing. Trends Pharmacol Sci 25(12):613–617. https://doi.org/10.1016/j.tips.2004.10.002.
Bagdy E, Kiraly I, Harsing LG (2000) Reciprocal Innervation between Serotonergic and GABAergic Neurons in Raphe Nuclei of the Rat. Neurochem 25:1465–1473. https://doi.org/10.1023/A:1007672008297.
Bliercrow P, Piñeyro G, el Mansari M, Bergeron R, de Montigny C (1998) Role of somatodendritic 5-HT autoreceptors in modulating 5-HT neurotransmission. Ann N Y Acad Sci 861:204–216. https://doi.org/10.1111/j.1749-6632.1998.tb10192.x.
Kirby LG, Pernar L, Valentino RJ, Beck SG (2003) Distinguishing characteristics of serotonin and non-serotonin-containing cells in the dorsal raphe nucleus: electrophysiological and immunohistochemical studies. Neuroscience 116(3):669–683. https://doi.org/10.1016/s0306-4522(02)00584-5.
Lemos JC, Pan YZ, Ma X, Lamy C, Akanwa AC, Beck SG (2006) Selective 5-HT receptor inhibition of glutamatergic and GABAergic synaptic activity in the rat dorsal and median raphe. Eur J Neurosci 24(12):3415–3430. https://doi.org/10.1111/j.1460-9568.2006.05222.x.
Ganley RP, de Sousa MM, Werder K, Öztürk T, Mendes R, Ranucci M, Wildner H, Zeilhofer HU (2023) Targeted anatomical and functional identification of antinociceptive and pronociceptive serotonergic neurons that project to the spinal dorsal horn. Elife 12:e78689. https://doi.org/10.7554/eLife.78689.
Inyushkin AN, Merkulova NA, Orlova AO, Inyushkina EM (2010) Local GABAergic modulation of the activity of serotoninergic neurons in the nucleus raphe magnus. Neurosci Behav Physiol. 40(8):885–893. https://doi.org/10.1007/s11055-010-9337-x.
Li MH, Suchland KL, Ingram SL (2015) GABAergic transmission and enhanced modulation by opioids and endocannabinoids in adult rat rostral ventromedial medulla. J Physiol 593(1):217–230. https://doi.org/10.1113/jphysiol.2014.275701.
Abrams JK, Johnson PL, Hollis JH, Lowry CA (2004) Anatomic and functional topography of the dorsal raphe nucleus. Ann N Y Acad Sci 1018:46–57. https://doi.org/10.1196/annals.1296.005.
Wu JC, Ziea ET, Lao L, Lam EF, Chan CS, Liang AY, Chu SL, Yew DT, Berman BM, Sung JJ (2010) Effect of electroacupuncture on visceral hyperalgesia, serotonin and fos expression in an animal model of irritable bowel syndrome. J Neurogastroenterol Motil 16(3):306–314. https://doi.org/10.5056/jnm.2010.16.3.306.
Bi Z, Zhang S, Meng Y, Feng Y, Wang Y, Wang E, Pan X, Zhu R, Fan H, Pang S, Zhu L, Yuan J (2021) Female serotonin transporter-knockout rat: A potential model of irritable bowel syndrome. FASEB J 35(7):e21701. https://doi.org/10.1096/fj.202000007RRR.
Andersen E, Dafny N (1983) An ascending serotonergic pain modulation pathway from the dorsal raphe nucleus to the parafascicularis nucleus of the thalamus. Brain Res 269(1):57–67. https://doi.org/10.1016/0006-8993(83)90962-9.
Dugué GP, Lörincz ML, Lottem E, Audero E, Matias S, Correia PA, Léna C, Mainen ZF (2014) Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice. PLoS One 9(8):e105941. https://doi.org/10.1371/journal.pone.0105941.
Marinelli S, Schnell SA, Hack SP, Christie MJ, Wessendorf MW, Vaughan CW (2004) Serotonergic and nonserotonergic dorsal raphe neurons are pharmacologically and electrophysiologically heterogeneous. J Neurophysiol 92(6):3532–3537. https://doi.org/10.1152/jn.00437.2004.
Xie L, Wu H, Chen Q, Xu F, Li H, Xu Q, Jiao C, Sun L, Ullah R, Chen X (2022) Divergent modulation of pain and anxiety by GABAergic neurons in the ventrolateral periaqueductal gray and dorsal raphe. Neuropsychopharmacology. https://doi.org/10.1038/s41386-022-01520-0.
Liu X, He J, Jiang W, Wen S, Xiao Z (2023) The roles of periaqueductal gray and dorsal raphe nucleus dopaminergic systems in the mechanisms of thermal hypersensitivity and depression in mice. J Pain S1526–5900(23)00037–8. https://doi.org/10.1016/j.jpain.2023.02.004.
Li C, Sugam JA, Lowery-Gionta EG, McElligott ZA, McCall NM, Lopez AJ, McKlveen JM, Pleil KE, Kash TL (2016) Mu Opioid Receptor Modulation of Dopamine Neurons in the Periaqueductal Gray/Dorsal Raphe: A Role in Regulation of Pain. Neuropsychopharmacology 41(8):2122–2132. https://doi.org/10.1038/npp.2016.12.
Yu W, Pati D, Pina MM, Schmidt KT, Boyt KM, Hunker AC, Zweifel LS, McElligott ZA, Kash TL (2021) Periaqueductal gray/dorsal raphe dopamine neurons contribute to sex differences in pain-related behaviors. Neuron 109(8):1365–1380.e5. https://doi.org/10.1016/j.neuron.2021.03.001.