Neuropharmacology and analgesia Ketoprofen and antinociception in hypo-oestrogenic Wistar rats fed on a high sucrose diet Osmar Antonio Jaramillo-Morales, Josué Vidal Espinosa-Juárez, Betzabeth Anali García-Martínez, Francisco Javier López-Muñoz n Departamento de Farmacobiología, Cinvestav-Sede Sur, Delegación Tlálpan, México D.F. C.P.14330, Mexico article info Article history: Received 4 May 2016 Received in revised form 8 June 2016 Accepted 17 June 2016 Available online 23 June 2016 Keywords: High-sucrose diet Nociception Ketoprofen Efficacy abstract Non-steroidal anti-inflammatory drugs such as ketoprofen are the most commonly used analgesics for the treatment of pain. However, no studies have evaluated the analgesic response to ketoprofen in conditions of obesity. The aim of this study was to analyse the time course of nociceptive pain in Wistar rats with and without hypo-oestrogenism on a high sucrose diet and to compare the antinociceptive response using ketoprofen. Hypo-oestrogenic and naïve rats received a hyper caloric diet (30% sucrose) or water ad libitum for 17 weeks, the thermal nociception (“plantar test” method) and body weight were tested during this period. A biphasic response was observed: thermal latency decreased in the 4th week (hyperalgesia), while from 12th to 17th week, thermal latency increased (hypoalgesia) in hypo-oestro- genic rats fed with high sucrose diet compared with the hypo-oestrogenic control group. At 4th and 17th weeks, different doses of ketoprofen (1.8–100 mg/kg p.o.), were evaluated in all groups. The adminis- tration of ketoprofen at 4th and 17th weeks showed dose-dependent effects in the all groups; however, a greater pharmacological efficacy was observed in the 4th week in the hypo-oestrogenic animals that received sucrose. Nevertheless, in all the groups significantly diminish the antinociceptive effects in the 17th week. Our data showed that nociception was altered in the hypo-oestrogenic animals that were fed sucrose (hyperalgesia and hypoalgesia). Ketoprofen showed a dose-dependent antinociceptive effect at both time points. However, hypo-oestrogenism plus high-sucrose diet modifies the antinociceptive effect of ketoprofen. & 2016 Elsevier B.V. All rights reserved. 1. Introduction Pain is a condition that affects thousands of people in the world. However, it has been shown that individuals with increased body weight are more likely to have problems with pain (Marcus, 2004; Wilson et al., 2010). Controversies exist regarding the per- ception of pain in obese subjects. Some studies report a hyper- algesic state associated with obesity (Roane and Martin, 1990; Sugimoto et al., 2008; Buchenauer et al., 2009), while others have proposed the existence of hypoalgesic processes (Ramzan et al., 1993; Zhang et al., 1994; Sugimoto et al., 2008). Moreover, the most frequent cases that have been documented clinically in obese people involve back pain (Hitt et al., 2007; D’Arcy, 2011) and arthritis pain (Marcus, 2004), triggered mainly due to a mechan- ical effect on the joints by weight gain. Obesity has also been as- sociated with other chronic pain conditions, such as migraine and headache (Goadsby et al., 2002; Rossi et al., 2013). For this reason, it is common for these patients to be treated with analgesic drugs. The most widespread drug therapy currently used to relieve no- ciceptive and inflammatory pain involves the non-steroidal anti- inflammatory analgesics (NSAIDs) and opioids (Ong et al., 2007). NSAIDs are the most widely prescribed drugs in clinical medicine; they are heterogeneous substances with varying nonsteroidal chemical structures (Laine, 2001). This group of drugs, which are indicated in the treatment of acute and chronic pain (Whiteside et al., 2004; Ong et al., 2007), is characterized by analgesic anti- inflammatory and antipyretic properties (Dworkin y Gitlin, 1991). Ketoprofen is a member of this group. As other NSAIDs, ketoprofen exerts its analgesic effect through at least three mechanisms of action, clearly identified as: 1) inhibition of prostaglandin synth- esis (Avouac and Teule, 1988; Kubota et al., 1997), 2) interaction with the serotonergic system (Díaz-Reval et al., 2001, 2004) and 3) inhibition of proinflammatory cytokines (Choi et al., 2013). Preclinical studies have indicated that ketoprofen exhibits Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/ejphar European Journal of Pharmacology http://dx.doi.org/10.1016/j.ejphar.2016.06.030 0014-2999/& 2016 Elsevier B.V. All rights reserved. n Correspondence to: Lab. No. 7 “Dolor y Analgesia” del Departamento de Farm- acobiología, Cinvestav-Sede Sur, Calz. de los Tenorios No. 235 Col. Granjas Coapa, Delegación Tlálpan, México D.F. C.P. 14330, Mexico. E-mail addresses: oajmorales@gmail.com (O.A. Jaramillo-Morales), jvidalespinosa@gmail.com (J.V. Espinosa-Juárez), qfbetzy@hotmail.com (B.A. García-Martínez), flopez@cinvestav.mx, flopezm@prodigy.net.mx (F.J. López-Muñoz). European Journal of Pharmacology 788 (2016) 168–175