Abstract
The serotoninergic system modulates nociceptive and locomotor spinal cord circuits. Exercise improves motor function and changes dopaminergic, noradrenergic, and serotonergic central systems. However, the direct relationship between serotonin, peripheral nerve lesion and aerobic treadmill exercise has not been studied. Using immunohistochemistry and optic densitometry, this study showed that the sciatic nerve transection increased the serotoninergic immunoreactivity in neuronal cytoplasm of the magnus raphe nuclei of trained and sedentary rats. In the dorsal raphe nucleus the increase only occurred in sedentary-sham-operated rats. In the spinal cord of trained, transected rats, the ventral horn showed significant changes, while the change in dorsal horn was insignificant. Von Frey’s test indicated analgesia in all exercise-trained rats. The sciatic nerve functional index indicated recovery in the trained group. Thus, both the aerobic treadmill exercise training and the nervous lesion appear to contribute to changes in serotonin immunoreactivity.
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Herbison GJ, Jaweed MM, Diturnno JF (1983) Exercise therapies in peripheral neuropathies. Arch Phys Med Rehabil 64:201–205
Linderman E, Leffers P, Spaans F et al (1995) Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial. Arch Phys Med Rehabil 76:612–620
Wright NC, Kilmer DD, McCrory MA et al (1996) Aerobic walking in slowly progressive neuromuscular disease: effect of a 12-week program. Arch Phys Med Rehabil 77:64–69
Hutchinson K, Gómez-Pinilla F, Crowe MJ et al (2004) Three exercise paradigms differentially improve sensory recovery after spinal cord contusion in rats. Brain 127:1403–1414
O’Conner PJ, Cook DB (1999) Exercise and pain: the neurobiology measurement, and laboratory study of pain in relation to exercise in humans. Exerc Sport Sci Rev 27:119–166
Hoffman MD, Shepanski MA, Ruble SB et al (2004) Intensity and duration threshold for aerobic exercise-induced analgesia to pressure pain. Arch Phys Med Rehabil 85:1183–1187
Hosseini M, Alaei HA, Naderi A et al. (2009) Treadmill exercise reduces self-administration of morphine in male rats. Pathophysiology 16:3–7
Droste C, Greenlee MW, Schreck M, Roskamm H (1991) Experimental pain thresholds and plasma beta-endorphin levels during exercise. Med Sci Sports Exerc 23:334–342
Koltyn KF (2002) Exercise-induce hypoalgesia and intensity of exercise. Sports Med 32:477–487
Meeusen R, De Meirleir K (1995) Exercise and brain neurotransmission. Sports Med 20:160–188
Barbeau H, Rossignol S (1990) The effects of serotonergic drugs on the locomotor pattern and on cutaneous reflexes of the adult chronic spinal cat. Brain Res 514:55–67
Crown E, Grau JW (2005) Evidence that descending serotonergic systems protect spinal cord plasticity against the distruptive effect of uncontrollable stimulation. Exp Neurol 196:164–176
LeBars D (1988) Serotonin and pain. In: Osborne NN, Hamon M (eds) Neuronal serotonin. Wiley, New York, pp 171–226
Jacobs BL, Fornal CA (1995) Activation of 5-HT neuronal activity during motor behavior. Neuroscience 7:401–408
Green GM, Scarth J, Dieckenson A (2000) An excitatory role for 5-HT in spinal inflamatory nociceptive transmission; state-dependent actions via dorsal horn 5-HT(3) receptors in the anaesthetized rat. Pain 89:81–88
Suzuki R, Rygh LJ, Dieckenson AH (2004) Bad news from the brain: descending 5-HT pathways that control spinal pain processing. Trends Pharmacol Sci 25:613–617
Rahman W, Suzuki R, Webber M et al (2006) Depletion of endogenous spinal 5HT attenuates the behavioral hypersensitivity to mechanical cooling stimuli induced by spinal nerve ligation. Pain 123:264–274
Fields HL, Basbaum AI (1994) Central nervous system mechanisms of pain modulation. In: Wall PD, Melzack R (eds) Textbook of pain, 3rd edn. Churchill Livingstone, Edinburgh, pp 243–257
Jacobs BL, Martin-Cora FJ, Fornal CA (2002) Activity of medullary serotonergic neurons in freely moving animals. Brain Res Rev 40:45–52
Holstege G, Kuypers HGJM (1987) Brainstem projections to spinal motoneurons: an update. Neuroscience 23:809–821
Jankowska E, Hammar I, Chojnicka B et al (2000) Effect of monoamines on interneurons in four spinal reflex pathways from group I and/or group II muscle afferents. Eur J Neurosci 12:701–714
Guilbaud G, Peschanski M, Gautron M et al (1980) Response of neurons of the nucleus raphe magnus to noxious stimuli. Neurosci Lett 17:149–154
Auerbach S, Fornal C, Jacobs B (1985) Response of serotonin-containing neurons in nucleus raphe magnus to morphine, noxiousstimuli, and periaqueductal gray stimulation in freely moving cats. Exp Neurol 88:609–628
Hains BC, Everhart AW, Fullwood SD et al (2002) Changes in serotonin, serotonin transporter expression and serotonin denervation supersensitivity involvement in chronic central pain after spinal hemisection in the rat. Exp Neurol 175:347–362
Horiuchi H, Ogata T, Morino T et al (2002) Serotonergic signaling inhibits hiperalgesia induced by spinal cord damage. Brain Res 963:312–320
Veasey SC, Fornal CA, Metzler CW et al (1997) Single-unit changes in responses of serotonergic dorsal raphe neurons to specific motor challenges in freely moving cats. Neuroscience 79:161–169
Schmidt BJ, Jordan LM (2000) The role of serotonin in reflex modulation and locomotor rhythm production in the mammalian spinal cord. Brain Res Bul 5:689–710
Gerin C, Teilhac JR, Smith K, Privat A (2008) Motor activity induces release of serotonin in the dorsal horn of the rat lumbar spinal cord. Neurosci Lett 436:91–95
Bement MH, Sluka KA (2005) Low- intensity exercise reverses chronic muscle pain in the rat in naloxone-dependent manner. Arch Phys Med Rehabil 86:1736–1740
Ruble SB, Hoffman MD, Shepanski MA et al (2005) Thermal pain perception after aerobic exercise. Arch Phys Med Rehabil 86:1019–1023
Alp P, Newsholme E, Zammit V (1976) Activities of citrate synthase and NAD+ -linked and NADP+ -linked isocitrate dehydrogenase in muscle from vertebrates and invertebrates. Biochem J 154:689–700
Ilha J, Araújo RT, Malysz T et al (2008) Endurance and resistance exercise training programs elicit specific effects on sciatic nerve regeneration after experimental traumatic lesion in rats. Neurorehabil Neural Repair 22:355–366
Partata W, Krepsky AMR, Xavier LL et al (1999) Distribution of glycogen phosphorylase and cytochrome oxidase in the central nervous system of the turtle Trachemys dorbigni. Comp Biochem Physiol A Mol Integr Physiol 124:113–122
Paxinos G, Watson C (1997) The rat brain in stereotaxic coordinates, 4th edn. Academic Press Inc., San Diego
Dey S, Singh RH, Dey PK (1992) Exercise training: significance of regional alterations in serotonin metabolism of rat brain in relation to antidepressant effect of exercise. Physiol Behav 52:1095–1099
Liu ZY, Zhuang DB, Lunderberg T et al (2002) Involvement of 5-Hydroxytryptamines1A receptors in the descending anti-nociceptive pathway from periaqueductal gray to the spinal dorsal in intact rats, rats with nerve injury and rats with inflammation. Neuroscience 112:399–407
Smith V, Beyer C, Brandt M (2005) Neurochemical changes in RMV associated with peripheral inflammatory pain stimuli. Brain Res 1095:65–67
Brow BS, Payne T, Kim C, Moore G et al (1979) Chronic response of rat brain norepinefrine and serotonin levels to endurance training. J Appl Physiol 46:19–23
Gerin C, Becquet D, Privat A (1995) Direct evidence for the link in-between monoaminergic descending pathways and motor activity. I. A study with microdialysis probes implanted in the ventral funiculus of the spinal cord. Brain Res 704:191–201
Millan JM (1999) The induction of pain: an integrative. Rev Prog Neurobiol 57:1–164
Heinricher MM, Tavares I, Leith JL et al (2008) Descending control of nociception: specifity recruitment and plasticity. Brain Res Rev 60:214–225
Suzuki R, Rahman W, Hunt SP et al (2004) Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury. Brain Res 1019:68–76
Huang WJ, Wang BR, Yao LB et al (2000) Activity of p44/42 MAP kinase in the caudal subnucleos of trigeminal spinal nucleos is increased following perioral noxious stimulation in the mouse. Brain Res 861:181–185
Ji RR, Babu H, Brenner GJ et al (2002) ERK MAP kinase activation in superficial spinal cord neurons contributes to pain hypersensitivity. J Neurosci 22:478–485
Imbe H, Okamoto K, Okamura T, Kumabe S, Nakatsuka M, Aikawa F, Iwaii-Liao Y, Senba E (2005) Effects of peripheral inflammation on activation of ERK in the rostral ventromedial medulla. Brain Res 1063:151–158
Rivot JP, Pointis D, Besson JM (1988) Morphine increase 5-HT metabolism in the nucleus raphe magnus: an in vivo study in freely moving rats using 5-hydroxyindole electrochemical detection. Brain Res 446:333–342
Tao R, Auerbach SB (1995) Involvement of dorsal raphe but not median raphe nucleus in morphine-induced increases in serotonin release in the rat forebrain. Neuroscience 68:553–561
Jacobs BL, Azmitia EC (1992) Structure and function of the serotonin system. Physiol Rev 72:165–229
Fornal CA, Martin-Cora FJ, Jacobs BL (2006) “Fatigue” of medullary but not mesencephalic raphe serotonergic neurons during locomotion in cats. Brain Res 1072:55–61
Xie W, Strong JA, Meij JTA et al (2004) Neuropatic pain: early afferent activity is the trigger. Pain 116:234–256
Fuchs A, Rigaud M, Hogan QH (2007) Painful nerve injury shortens the intracellular Ca+2 signal in axotomized sensory neurons of rats. Anesthesiology 107:106–116
Tyce GM, Yaksh TL (1981) Monoamina release from cat spinal cord by somatic stimuli: an intrinsic modulatory system. J Physiol 314:513–529
Gutmann E, Jakoubek B (1963) Effect of increased motor activity on regeneration of the peripheral nerve in young rats. Physiol Bohemoslov 12:463–468
Eisen AA, Carpenter S, Karpati G et al (1973) The effect of muscle hyper- and hypoactivity upon fibre diameters of intact and regenerating nerves. J Neurol Sci 20:457–469
Molteni R, Zheng J-Q, Ying Z, Gómez-Pinilla F, Twiss JL (2004) Voluntary exercise increases axonal regeneration from sensory neurons. Proc Natl Acad Sci USA 101:8473–8478
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This study was supported by grants from Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Coordenação de Aperfeiçoamento de pessoal de nível Superior (CAPES).
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Korb, A., Bonetti, L.V., da Silva, S.A. et al. Effect of Treadmill Exercise on Serotonin Immunoreactivity in Medullary Raphe Nuclei and Spinal Cord Following Sciatic Nerve Transection in Rats. Neurochem Res 35, 380–389 (2010). https://doi.org/10.1007/s11064-009-0066-x
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DOI: https://doi.org/10.1007/s11064-009-0066-x