Abstract
Analgesia may be modulated by multiple internal and external factors. In prior studies, copulatory-induced analgesia was demonstrated using the vocalization threshold to tail shock (VTTS) in male and female rats. Three ejaculatory endophenotypes have been characterized in male Wistar rats based upon their ejaculation latency (EL). Since intromissions and ejaculations produce analgesia, and these copulatory patterns are performed with different frequency depending on the male’s ejaculatory endophenotype, we hypothesized that copulation-induced analgesia would vary in relation to these endophenotypes. In the present study, we used three groups according to the EL (medians): rapid ejaculators (236 s; n = 21), intermediate ejaculators (663.2 s; n = 20) and sluggish ejaculators (1582.2 s; n = 8). Our aim was to evaluate whether copulation-induced analgesia is related to the ejaculatory endophenotypes during two consecutive ejaculatory series (EJS). In the first EJS, the VTTS of the rapid ejaculators was significantly higher than that of intermediate and sluggish rats. At the onset of the second EJS, the VTTS of the rapid and intermediate ejaculators was significantly higher than that of the sluggish rats. No differences in VTTS were observed during the first or second post-ejaculatory intervals among the three groups. These findings provide evidence that the more intromissions that occurred per unit time, the higher was the level of analgesia.
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References
Yaksh T. The effects of intrathecal administered opioid and adrenergic agents of spinal function. In: Yaksh T, editor. Spinal afferent processing. New York: Plenum Press; 1986. p. 505–39. https://doi.org/10.1007/978-1-4684-4994-5.
Szechtman H, Hershkowitz M, Simantov R. Sexual behavior decreases pain sensitivity and stimulates endogenous opioids in male rats. Eur J Pharmacol. 1981;70:279–85. https://doi.org/10.1016/0014-2999(81)90161-8.
Forsberg G, Wiesenfeld-Hallin Z, Eneroth P, Södersten P. Sexual behavior induces naloxone-reversible hypoalgesia in male rats. Neurosci Lett. 1987;81:151–4. https://doi.org/10.1016/0304-3940(87)90356-9.
González-Mariscal G, Gómora P, Caba M, Beyer C. Copulatory analgesia in male rats ensues from arousal, motor activity, and genital stimulation: blockage by manipulation and restraint. Physiol Behav. 1992;51:775–81. https://doi.org/10.1016/0031-9384(92)90115-I.
González-Mariscal G, Gómora P, Beyer C. Participation of opiatergic, GABAergic, and serotonergic systems in the expression of copulatory analgesia in male rats. Pharmacol Biochem Behav. 1994;49:303–7. https://doi.org/10.1016/0091-3057(94)90425-1.
Saldívar-González A, Fernández-Guasti A. Ejaculation induced changes in escape latency in the hot plate test: pharmacological analysis of anxiolytic versus analgesic effect. Behav Brain Res. 1994;60:191–8. https://doi.org/10.1016/0166-4328(94)90147-3.
Sachs BD, Barfield RJ. Functional analysis of masculine copulatory behavior in the rat. In: Rosenblatt JS, Hinde RA, Shaw E, Beer C, editors. Advances in the Study of Behavior, vol 7. Academic Press;1976. p. 91–154. https://doi.org/10.1016/S0065-3454(08)60166-7.
Pattij T, Olivier B, Waldinger M. Animal models of ejaculatory behavior. Curr Pharm Des. 2005;145:10–20. https://doi.org/10.2174/138161205774913363.
Olivier B, Chan JSW, Pattij T, de Jong TR, Oosting RS, Veening JG, et al. Psychopharmacology of male rat sexual behavior: modeling human sexual dysfunctions?, Int J Impot Res. 2006:S14–S23. https://doi.org/10.1038/sj.ijir.3901330.
Borgdorff AJ, Rössler AS, Clément P, Bernabé J, Alexandre L, Giuliano F. Differences in the spinal command of ejaculation in rapid ejaculating rats. J Sex Med. 2009;6:2197–205. https://doi.org/10.1111/j.1743-6109.2009.01308.x.
Zipse LR, Brandling-Bennett EM, Clark AS. Paced mating behavior in the naturally cycling and the hormone-treated female rat. Physiol Behav. 2000;70:205–9. https://doi.org/10.1016/S0031-9384(00)00242-0.
Lucio RA, Rodríguez-Piedracruz V, Tlachi-López JL, García-Lorenzana M, Fernández-Guasti A. Copulation without seminal expulsion: the consequence of sexual satiation and the Coolidge effect. Andrology. 2014;2:450–7. https://doi.org/10.1111/j.2047-2927.2014.00209.x.
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8:e1000412 https://doi.org/10.1371/journal.pbio.1000412.
Zhang HF, Zhang CY, Li XH, Fu ZZ, Chen ZY. Dorsal penile nerves and primary premature ejaculation. Chin Med J. 2009;122:3017–9. https://doi.org/10.3760/cma.j.issn.0366-6999.2009.24.020.
Zhang GX, Yu LP, Bai WJ, Wang XF. Selective resection of dorsal nerves of penis for premature ejaculation. Int J Androl. 2012;35:873–9. https://doi.org/10.1111/j.1365-2605.2012.01296.x.
Guo L, Liu Y, Wang X, Yuan M, Yu Y, Zhang X, et al. Significance of penile hypersensitivity in premature ejaculation. Sci Rep. 2017;7:10441–6. https://doi.org/10.1038/s41598-017-09155-8.
Paick JS, Jeong H, Park MS. Penile sensitivity in men with premature ejaculation. Int J Impot Res. 1998;10:247–50. https://doi.org/10.1038/sj.ijir.3900368.
Segura B, Melo AI, Fleming AS, Mendoza-Garrido ME, González del Pliego M, Aguirre-Benitez EL, et al. Early social isolation provokes electrophysiological and structural changes in cutaneous sensory nerves of adult male rats. Dev Neurobiol. 2014;74:1184–93. https://doi.org/10.1002/dneu.22197.
Lenz KM, Sengelaub DR. Maternal licking influences dendritic development of motoneurons in a sexually dimorphic neuromuscular system. Brain Res. 2006;1092:87–99. https://doi.org/10.1016/j.brainres.2006.03.070.
Lenz KM, Graham MD, Parada M, Fleming AS, Sengelaub DR, Monks DA. Tactile stimulation during artificial rearing influences adult function and morphology in a sexually dimorphic neuromuscular system. Dev Neurobiol. 2008;68:542–57. https://doi.org/10.1002/dneu.20608.
Qureshi GA, Södersten P. Sexual activity alters the concentration of amino acids in the cerebrospinal fluid of male rats. Neurosci Lett. 1986;70:374–8. https://doi.org/10.1016/0304-3940(86)90582-3.
Hull EM, Bitran D, Pehek EA, Warner RK, Band LC, Holmes GM. Dopaminergic control of male sex behavior in rats: effects of an intracerebrally-infused agonist. Brain Res. 1986;370:73–81. https://doi.org/10.1016/0006-8993(86)91106-6.
Fernández-Guasti A, Larsson K, Beyer C. GABAergic control of masculine sexual behavior. Pharmacol Biochem Behav. 1986;24:1065–70. https://doi.org/10.1016/0091-3057(86)90456-9.
Sawynok J. GABAergic mechanisms of analgesia: an update. Pharmacol Biochem Behav. 1987;26:463–74. https://doi.org/10.1016/0091-3057(87)90148-1.
Agmo A, Paredes R. Opioids and sexual behavior in the male rat. Pharmacol Biochem Behav. 1988;30:1021–34. https://doi.org/10.1016/0091-3057(88)90135-9.
Veening JG, Coolen LM. Neural mechanisms of sexual behavior in the male rat: emphasis on ejaculation-related circuits. Pharmacol Biochem Behav. 2014;121:170–83. https://doi.org/10.1016/j.pbb.2013.12.017.
Basbaum AI, Fields HL. Endogenous pain control mechanisms: review and hypothesis. Ann Neurol. 1978;4:451–62. https://doi.org/10.1002/ana.410040511.
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009;139:267–84. https://doi.org/10.1016/j.cell.2009.09.028.
Waldinger MD. The neurobiological approach to premature ejaculation. J Urol. 2002;168:2359–67. https://doi.org/10.1016/S0022-5347(05)64146-8.
Agmo A, Berenfeld R. Reinforcing properties of ejaculation in the male rat: role of opioids and dopamine. Behav Neurosci. 1990;104:177–82. https://doi.org/10.1037/0735-7044.104.1.177.
Lupica CR, Riegel AC. Endocannabinoid release from midbrain dopamine neurons: a potential substrate for cannabinoid receptor antagonist treatment of addiction. Neuropharmacology. 2005;48:1105–16. https://doi.org/10.1016/j.neuropharm.2005.03.016.
Rodríguez-Manzo G, Canseco-Alba A. Anandamide reduces the ejaculatory threshold of sexually sluggish male rats: possible relevance for human lifelong delayed ejaculation disorder. J Sex Med. 2015;12:1128–35. https://doi.org/10.1111/jsm.12866.
Rice ASC, Farquhar-Smith WP, Nagy I. Endocannabinoids and pain: spinal and peripheral analgesia in inflammation and neuropathy. Prostag Leukotr Ess Fat Acids. 2002;66:243–56. https://doi.org/10.1054/plef.2001.0362.
Sorkins LS, McAdoo DJ, Willis WD. Raphe magnus stimulation-induced antinociception in the cat is associated with release of amino acids as well as serotonin in the lumbar dorsal horn. Brain Res. 1993;618:95–108. https://doi.org/10.1016/0006-8993(93)90433-n.
Hammond DL, Levy RA, Proudfit HK. Hypoalgesia induced by microinjection of a norepinephrine antagonist in the nucleus raphe magnus: reversal by intrathecal administration of a serotonin antagonist. Brain Res. 1980;201:475–9. https://doi.org/10.1016/0006-8993(80)91056-2.
Jacobs BL Central monoaminergic neurons: single-unit studies in behaving animals. In: Meltzer HY, editor. Psychopharmacology. 3rd ed. New York: Raven Press; 1987. p. 159–69. https://doi.org/10.1002/mds.870040114.
Gintzler AR, Peters LC, Komisaruk BR. Attenuation of pregnancy-induced analgesia by hypogastric neurectomy in rats. Brain Res. 1983;277:186–8. https://doi.org/10.1016/0006-8993(83)90924-1.
Roberts LA, Beyer C, Komisaruk BR. Nociceptive responses to altered GABAergic activity at the spinal cord. Life Sci. 1986;39:1667–74. https://doi.org/10.1016/0024-3205(86)90164-5.
Mantyh PW, Peschanski M. Spinal projections from the periaqueductal grey and dorsal raphe in the rat, cat and monkey. Neuroscience. 1982;7:2769–76. https://doi.org/10.1016/0306-4522(82)90099-9.
Moss MS, Basbaum AI. The peptidergic organization of the cat periaqueductal grey. II. The distribution of immunoreactive substance P and vasoactive intestinal polypeptide. J Neurosci. 1983;3:1437–49. https://doi.org/10.1523/JNEUROSCI.03-07-01437.1983.
McKenna KE, Nadelhaft I. The organization of the pudendal nerve in the male and female rat. J Comp Neurol. 1985;248:532–49. https://doi.org/10.1002/cne.902480406.
Swanson LW, Kuypers HGJM. 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. 1980;194:555–70. https://doi.org/10.1002/cne.901940306.
Argiolas A, Melis MR. The role of oxytocin and the paraventricular nucleus in the sexual behaviour of male mammals. Physiol Behav. 2004;83:309–17. https://doi.org/10.1016/j.physbeh.2004.08.019.
Véronneau-Longueville F, Rampin O, Freund-Mercier MJ, Tang Y, Calas A, Marson L, et al. Oxytocinergic innervation of autonomic nuclei controlling penile erection in the rat. Neuroscience. 1999;395:247–54. https://doi.org/10.1016/S0306-4522(99)00262-6.
Baskerville TA, Allard J, Wayman C, Douglas AJ. Dopamine-oxytocin interactions in penile erection. Eur J Neurosci. 2009;30:2151–64. https://doi.org/10.1111/j.1460-9568.2009.06999.x.
Rojas-Piloni G, López-Hidalgo M, Martínez-Lorenzana G, Rodríguez-Jiménez J, Condés-Lara M. GABA-mediated oxytocinergic inhibition in dorsal horn neurons by hypothalamic paraventricular nucleus stimulation. Brain Res. 2007;1137:69–77. https://doi.org/10.1016/j.brainres.2006.12.045.
González-Hernández A, Rojas-Piloni G, Condés-Lara M. Oxytocin and analgesia: future trends. Trends Pharmacol Sci. 2014;35:549–51. https://doi.org/10.1016/j.tips.2014.09.004.
Futagami H, Sakuma Y, Kondo Y. Oxytocin mediates copulation-induced hypoalgesia of male rats. Neurosci Lett. 2016;618:122–6. https://doi.org/10.1016/j.neulet.2016.03.007.
Komisaruk BR, Larsson K. Suppression of a spinal and a cranial nerve reflex by vaginal or rectal probing in rats. Brain Res. 1971;35:231–5. https://doi.org/10.1016/0006-8993(71)90608-1.
Sansone GR, Gerdes CA, Steinman JL, Winslow JT, Ottenweller JE, Komisaruk BR, et al. Vaginocervical stimulation releases oxytocin within the spinal cord in rats. Neuroendocrinology. 2002;75:306–15. https://doi.org/10.1159/000057340.
Komisaruk BR, Sansone G. Neural pathways mediating vaginal function: the vagus nerves and spinal cord oxytocin. Scand J Psychol. 2003;44:241–50. https://doi.org/10.1111/1467-9450.00341.
Gómora P, González-Flores O, Galicia-Aguas YL, Hoffman KL, Komisaruk BR. Copulation-induced antinociception in female rats is blocked by atosiban, an oxytocin receptor antagonist. Horm Behav. 2019;107:76–79. https://doi.org/10.1016/J.YHBEH.2018.12.001.
Acknowledgements
We thank the “Posgrado en Ciencias Biológicas” of the Universidad Autónoma de Tlaxcala for the training received during the Doctorate studies.
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This research was partially supported by PROMEP/103.5/09/1294, and CONACYT [grant 1134291 (OGF), and fellowships 487025/277841 (CEAP) and 400424 (MRFM)].
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Aguilar-Pérez, C.E., Gómora-Arrati, P., Komisaruk, B.R. et al. Threshold for copulation-induced analgesia varies according to the ejaculatory endophenotypes in rats. Int J Impot Res 34, 195–202 (2022). https://doi.org/10.1038/s41443-020-00390-8
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DOI: https://doi.org/10.1038/s41443-020-00390-8
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