Farmacogenética y respuesta analgésica: hacia una medicina personalizada con análisis de las diferencias por sexo

• Autores: Beatriz Orts Jorquera, Javier Muriel Serrano, Ana M. Peiró Peiró
• Localización: Revista de la Sociedad Española del Dolor (SED), ISSN 1134-8046, Vol. 30, Nº. 2, 2023, págs. 115-124
• Idioma: español
• DOI: 10.20986/resed.2023.4042/2022
• Títulos paralelos:
  • Pharmacogenetics in analgesic response: towards a sex-differences personalized medicine
• Enlaces
  • Texto completo
• Resumen
  • español

    El dolor crónico supone una epidemia silenciosa que afecta a 1 de cada 5 personas adultas en Europa. Este hecho convive con el abuso que realizan algunos pacientes de los medicamentos analgésicos, circunstancia que está limitando su prescripción en el dolor crónico no oncológico. El reto sería poder seleccionar las personas que, a priori, tendrían una mejor respuesta analgésica en base a una serie de condicionamientos intrínsecos. La presente revisión analiza las diferencias en base al sexo y a la presencia de ciertas variantes en los genes que codifican el receptor opioide mu (OPRM1), la enzima metabolizadora del citocromo CYP2D6 y la catecol-O-metiltransferasa (COMT) que degrada catecolaminas. El objetivo es suministrar potenciales elementos explicativos que puedan orientar al profesional clínico en la selección de una analgesia más personalizada.

  • English

    Chronic pain is a silent epidemic, affecting 1 in 5 adults in Europe. This fact coexists with the abuse of analgesic drugs by some patients, a circumstance that is limiting their prescription in chronic non-cancer pain. The challenge would be to be able to select the people who, a priori, would have a better analgesic response based on a series of intrinsic conditions. This review analyzes the differences based on sex and the presence of certain variants in the genes that encode the mu opioid receptor (OPRM1), the cytochrome metabolizing enzyme CYP2D6 and the catechol-O-methyltransferase (COMT) that degrades catecholamines. The objective is to provide potentially explanatory elements that can guide the clinical professional in the selection of a more personalized analgesia.

• Referencias bibliográficas
  • Langley, PC,Ruiz-Iban, MA,Molina, JT,De Andres, J,Castellón, JR. (2011). The prevalence, correlates and treatment of pain in Spain. J Med...
  • Pérez, C,Margarit, C,Serrano, M. (2013). Survey of European patients assessing their own noncancer chronic pain: results from Spain. Curr...
  • Fillingim, RB,King, CD,Ribeiro-Dasilva, MC,Rahim-Williams, B,Riley, JL. (2009). Sex, gender, and pain: a review of recent clinical and experimental...
  • Bartley, EJ,Fillingim, RB. (2013). Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 111. 52
  • Darnall, BD,Stacey, BR,Chou, R. (2012). Medical and psychological risks and consequences of long-term opioid therapy in women. Pain Med. 13....
  • Planelles, B,Margarit, C,Inda, MD,Ballester, P,Muriel, J,Barrachina, J. (2020). Gender based differences, pharmacogenetics and adverse events...
  • Hutchinson, K,Moreland, AM,de Williams, ACC,Weinman, J,Horne, R. (2007). Exploring beliefs and practice of opioid prescribing for persistent...
  • Ballina, J,Carmona, L,Laffon, A. (2002). Impacto del consumo de AINE en la población general española Resultados del estudio EPISER. Rev Esp...
  • Chou, R,Fanciullo, GJ,Fine, PG,Adler, JA,Ballantyne, JC,Davies, P. (2009). Clinical guidelines for the use of chronic opioid therapy in chronic...
  • Larsson, B,Dragioti, E,Grimby-Ekman, A,Gerdle, B,Björk, J. (2019). Predictors of chronic pain intensity, spread, and sensitivity in the general...
  • (2018). Canadian Institutes of Health Research. Science is better with sex and gender.
  • Pisanu, C,Franconi, F,Gessa, GL,Mameli, S,Pisanu, GM,Campesi, I. (2019). Sex differences in the response to opioids for pain relief: A systematic...
  • Gallach Solano, E,Bermejo Gómez, MA,Robledo Algarra, R,Izquierdo Aguirre, RM,Canos Verdecho, MA. (2020). Determinantes de género en el abordaje...
  • Kiely, KM,Brady, B,Byles, J. (2019). Gender, mental health and ageing. Maturitas. 129. 76-84
  • Sorge, RE,Mapplebeck, JC,Rosen, S,Beggs, S,Taves, S,Alexander, JK. (2015). Different immune cells mediate mechanical pain hypersensitivity...
  • Samulowitz, A,Gremyr, I,Eriksson, E,Hensing, G. (2018). "Brave Men" and "Emotional Women": A Theory-Guided Literature Review...
  • Richardson, J,Holdcroft, A. (2009). Gender differences and pain medication. Women's health (London, England). 5. 79-90
  • (2003). ScienceDaily Sex, Hormones & Genetics Affect Brain's Pain Control System. ScienceDaily.
  • Saiz-Rodríguez, M,Ochoa, D,Herrador, C,Belmonte, C,Román, M,Alday, E. (2019). Polymorphisms associated with fentanyl pharmacokinetics, pharmacodynamics...
  • Manubay, J,Davidson, J,Vosburg, S,Jones, J,Comer, S,Sullivan, M. (2015). Sex differences among opioid-abusing patients with chronic pain in...
  • Muriel, J,Margarit, C,Barrachina, J,Ballester, P,Flor, A,Morales, D. (2019). Pharmacogenetics and prediction of adverse events in prescription...
  • Escorial, JM,Barrachina, J,Margarit, C,Agulló, L,Peiró, AM. (2021). Efectividad a largo plazo de la deprescripción en pacientes con dependencia...
  • Lopes, GS,Bielinski, S,Moyer, AM,Jacobson, DJ,Wang, L,Jiang, R. (2021). Sex differences in type and occurrence of adverse reactions to opioid...
  • Serdarevic, M,Striley, CW,Cottler, LB. (2017). Sex differences in prescription opioid use. Current opinion in psychiatry. 30. 238
  • Back, SE,Payne, RA,Waldrop, AE,Smith, A,Reeves, S,Brady, KT. (2009). Prescription opioid aberrant behaviors: a pilot study of sex differences....
  • Holgado, D,Manresa-Rocamora, A,Zamboni, L,Lugoboni, F,Peiró, AM,Zandonai, T. (2021). The effect of benzodiazepines on exercise in healthy...
  • McHugh, RK,Geyer, RB,Chase, AR,Griffin, ML,Bogunovic, O,Weiss, RD. (2021). Sex differences in benzodiazepine misuse among adults with substance...
  • McLean, CP,Anderson, ER. (2009). Brave men and timid women A review of the gender differences in fear and anxiety. Clin Psychol Rev. 29. 496-505
  • Gemmati, D,Varani, K,Bramanti, B,Piva, R,Bonaccorsi, G,Trentini, A. (2019). "Bridging the Gap" Everything that Could Have Been Avoided...
  • Sato, H,Droney, J,Ross, J,Olesen, AE,Staahl, C,Andresen, T. (2013). Gender, variation in opioid receptor genes and sensitivity to experimental...
  • Cabaleiro, T,Ochoa, D,Román, M,Moreno, I,López-Rodríguez, R,Novalbos, J. (2015). Polymorphisms in CYP2D6 have a greater effect on variability...
  • Muriel, J,Margarit, C,Planelles, B,Serralta, MJ,Puga, C,Inda, MD. (2018). OPRM1 influence on and effectiveness of an individualized treatment...
  • Campbell, CI,Weisner, C,Leresche, L,Ray, GT,Saunders, K,Sullivan, MD. (2010). Age and gender trends in long-term opioid analgesic use for...
  • Back, SE,Lawson, KM,Singleton, LM,Brady, KT. (2011). Characteristics and correlates of men and women with prescription opioid dependence....
  • Back, SE,Payne, RL,Simpson, AN,Brady, KT. (2010). Gender and prescription opioids: findings from the National Survey on Drug Use and Health....
  • Aloisi, AM. (2017). Why We Still Need To Speak About Sex Differences and Sex Hormones in Pain. Pain Ther. 6. 111
  • Vázquez-Santiago, S,Garrido Peña, F. (2016). El enfoque de género en las necesidades de atención sociosanitaria. Enferm Clín. 26. 76-80
  • (2010). Organización Panamericana de la Salud. GÉNERO Y SALUD: una Guía Práctica para la Incorporación de la Perspectiva de Género en Salud....
  • (2018). European Medicines Agency: Committee for Medicinal Products for Human Use (CHMP) Guideline on good pharmacogenomic practice. European...
  • (2020). Table of Pharmacogenomic Biomarkers in Drug Labeling. U.S. Food and Drug Administration.
  • Lin, YS,Thummel, KE,Thompson, BD,Totah, RA,Cho, CW. (2021). Sources of Interindividual Variability. Methods Mol Biol. 2342. 481-550
  • Alomar, MJ. (2014). Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm J. 22. 83-94
  • Roden, DM,McLeod, HL,Relling, MV,Williams, MS,Mensah, GA,Peterson, JF. (2019). Pharmacogenomics. Lancet. 394. 521
  • Crews, KR,Monte, AA,Huddart, R,Caudle, KE,Kharasch, ED,Gaedigk, A. (2021). Clinical Pharmacogenetics Implementation Consortium Guideline for...
  • Somogyi, AA,Coller, JK,Barratt, DT. (2015). Pharmacogenetics of opioid response. Clin Pharmacol Ther. 97. 125
  • Reynolds, KK,Ramey-Hartung, B,Jortani, SA. (2008). The value of CYP2D6 and OPRM1 pharmacogenetic testing for opioid therapy. Clin Lab Med....
  • Benjeddou, M,Peiró, AM. (2021). Pharmacogenomics and prescription opioid use. Pharmacogenomics. 22. 235
  • Kwon, AH,Flood, P. (2020). Genetics and Gender in Acute Pain and Perioperative Opioid Analgesia. Anesthesiol Clin. 38. 341
  • Chou, WY,Yang, LC,Lu, HF,Ko, JY,Wang, CH,Lin, SH. (2006). Association of mu-opioid receptor gene polymorphism (A118G) with variations in morphine...
  • Mague, SD,Isiegas, C,Huang, P,Liu-Chen, LY,Lerman, C,Blendy, JA. (2009). Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects...
  • Liu, A,Zhang, H,Qin, F,Wang, Q,Sun, Q,Xie, S. (2018). Sex Associated Differential Expressions of the Alternatively Spliced Variants mRNA of...
  • Collins, D,Zhang, Y,Blendy, J,Kreek, MJ. (2020). Murine model of OPRM1 A118G alters oxycodone self-administration and locomotor activation,...
  • Reyes-Gibby, CC,Shete, S,Rakvag, T,Bhat, SV,Skorpen, F,Bruera, E. (2007). Exploring joint effects of genes and the clinical efficacy of morphine...
  • Meloto, CB,Bortsov, AV,Bair, E,Helgeson, E,Ostrom, C,Smith, SB. (2016). Modification of COMT-dependent pain sensitivity by psychological stress...
  • Smith, HS. (2009). Opioid metabolism. Mayo Clin Proc. 84. 613
  • He, ZX,Chen, XW,Zhou, ZW,Zhou, SF. (2015). Impact of physiological, pathological and environmental factors on the expression and activity...
  • Gaedigk, A,Simon, SD,Pearce, RE,Bradford, LD,Kennedy, MJ,Leeder, JS. (2008). The CYP2D6 activity score: translating genotype information into...
  • Naranjo, ME,de Andrés, F,Delgado, A,Cobaleda, J,Peñas-Lledó, EM. (2016). High frequency of CYP2D6 ultrarapid metabolizers in Spain: controversy...
  • Matic, M,de Wildt, SN,Tibboel, D,van Schaik, RHN. (2017). Analgesia and Opioids: A Pharmacogenetics Shortlist for Implementation in Clinical...
  • Owusu Obeng, A,Hamadeh, I,Smith, M. (2017). Review of Opioid Pharmacogenetics and Considerations for Pain Management. Pharmacotherapy. 37....
  • Gray, K,Adhikary, SD,Janicki, P. (2018). Pharmacogenomics of analgesics in anesthesia practice: A current update of literature. J Anaesthesiol...
  • Linares, OA,Daly, D,Linares, AD,Stefanovski, D,Boston, RC. (2014). Personalized oxycodone dosing: using pharmacogenetic testing and clinical...
  • Naito, T,Takashina, Y,Yamamoto, K,Tashiro, M,Ohnishi, K,Kagawa, Y. (2011). CYP3A5*3 affects plasma disposition of noroxycodone and dose escalation...
  • Stamer, UM,Zhang, L,Book, M,Lehmann, LE,Stuber, F,Musshoff, F. (2013). CYP2D6 genotype dependent oxycodone metabolism in postoperative patients....
  • Andreassen, TN,Eftedal, I,Klepstad, P,Davies, A,Bjordal, K,Lundstrom, S. (2012). Do CYP2D6 genotypes reflect oxycodone requirements for cancer...
  • Balyan, R,Mecoli, M,Venkatasubramanian, R,Chidambaran, V,Kamos, N,Clay, S. (2017). CYP2D6 pharmacogenetic and oxycodone pharmacokinetic association...
  • Dagostino, C,Allegri, M,Napolioni, V,D'Agnelli, S,Bignami, E,Mutti, A. (2018). CYP2D6 genotype can help to predict effectiveness and safety...
  • Slanar, O,Dupal, P,Matouskova, O,Vondrackova, H,Pafko, P,Perlik, F. (2012). Tramadol efficacy in patients with postoperative pain in relation...
  • Wu, SB,Cai, LN,Yang, XH,Fu, HG,Sun, K,Yuan, F. (2015). Impact of CYP2D6 Polymorphisms on Postoperative Fentanyl Analgesia in Gastric Cancer...
  • Stauble, ME,Moore, AW,Langman, LJ,Boswell, MV,Baumgartner, R,McGee, S. (2014). Hydrocodone in postoperative personalized pain management:...
  • Mactier, H,McLaughlin, P,Gillis, C,Osselton, MD. (2017). Variations in Infant CYP2B6 Genotype Associated with the Need for Pharmacological...
  • Park, HJ,Choi, YJ,Kim, JW,Chun, HS,Im, I,Yoon, S. (2015). Differences in the Epigenetic Regulation of Cytochrome P450 Genes between Human...
  • Rostam-Abadi, Y,Gholami, J,Amin-Esmaeili, M,Safarcherati, A,Mojtabai, R,Ghadirzadeh, MR. (2020). Tramadol use and public health consequences...
  • Schelde, AB,Sørensen, AMS,Hindsø, M,Christensen, MB,Jimenez-Solem, E,Eriksson, R. (2020). Sex and age differences among tramadol users in...
  • Zandonai, T,Escorial, M,Peiró, AM. (2021). Codeine and Tramadol Use in Athletes: A Potential for Abuse. Front Pharmacol. 12.
  • Buynak, R,Shapiro, DY,Okamoto, A,Hove, IV,Rauschkolb, C,Steup, A. (2010). Efficacy and safety of tapentadol extended release for the management...
  • (2009). Hartrick CTJEoop Tapentadol immediate release for the relief of moderate-to-severe acute pain. Expert Opin Pharmacother. 10. 2687
  • Viñas-Bastart, M,Oms-Arias, M,Pedraza-Gutiérrez, À,Lizano-Díez, I,Mariño, EL,Modamio, P. (2021). Tapentadol and Oxycodone/Naloxone Prescribing...
  • Barrachina, J,Margarit, C,Muriel, J,López-Gil, S,López-Gil, V,Vara-González, A. (2022). Oxycodone/naloxone versus tapentadol in real-world...
  • Elder, NM,Atayee, RS,Best, BM,Ma, JD. (2014). Observations of urinary oxycodone and metabolite distributions in pain patients. J Anal Toxicol....