Toluene exposure enhances acute and chronic formalin-induced nociception in rats: Participation of 5-HT3 receptors.

The purpose of this study was to evaluate the effect of acute toluene exposure on formalin (0.5% and 1%)-induced acute and long-lasting nociceptive hypersensitivity in rats. In addition, we sought to investigate the role of peripheral 5-HT3 receptors in the pronociceptive effect of toluene. Toluene exposure (6000ppm) for 30min enhanced 0.5% or 1% formalin-induced acute nociception and long-lasting secondary allodynia and hyperalgesia. In contrast, exposition to toluene for 30min in rats previously injected (six days before) with 1% formalin did not affect long-lasting hypersensitivy. Local peripheral pre-treatment with alosetron (5-HT3 receptor antagonist, 10-100 nmol) reduced the pronociceptive effect of toluene in acute nociception and long-lasting secondary allodynia and hyperalgesia. Alosetron (100nmol) was also able to reduce the nociceptive effects of 1% formalin in absence of toluene. Moreover, local peripheral injection of m-CPBG (5-HT3 receptor agonist, 300 nmol) enhanced 0.5% formalin-induced acute and long-lasting nociception in air- and toluene-exposed rats. Alosetron (10nmol) blocked the pronociceptive effects of m-CPBG (300nmol) on 0.5% formalin-induced acute and long-lasting hypersensitivity in rats exposed to toluene. Alosetron (at 10nmol) did not modify formalin-induced nociceptive behaviors. Finally, local peripheral pre-treatment with methiothepin (non-selective 5-HT receptor antagonist, 1.5nmol), did not affect the pronociceptive effect of toluene on 1% formalin-induced acute and long-lasting hypersensitivity. Our data demonstrate that acute exposure to toluene has pronociceptive effects in formalin-induced acute nociception and long-lasting hypersensitivity. Our data suggest that this pronociceptive effect depend on activation of peripheral 5-HT3, but not methiothepin-sensitive 5-HT, receptors.

Combination of diacerhein and antiepileptic drugs after local peripheral, and oral administration in the rat formalin test.

Preclinical Research The present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin-induced nociception. Diacerhein, each of the antiepileptics or a fixed dose-ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. Diacerhein, antiepileptic drugs (carbamazepine, topiramate and gabapentin) or their combinations yielded a dose-dependent antinociceptive effect when administered by both routes. Theoretical ED30 values for the combination estimated from the isobolograms were obtained as follows: diacerhein-carbamazepine (85.99 ± 7.07 µg/paw; 56.53 ± 4.56 mg/kg po), diacerhein-topiramate (197.97 ± 22.90 µg/paw; 13.06 ± 2.44 mg/kg po) and diacerhein-gabapentin (96.87 ± 17.73 µg/paw; 17.90 ± 4.70 mg/kg p.o.) for the local peripheral and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED30 values: diacerhein-carbamazepine (49.33 ± 3.37 µg/paw; 35.49 ± 7.91 mg/kg po), diacerhein-topiramate (133.00 ± 39.10 µg/paw; 8.87 ± 1.46 mg/kg po) and diacerhein-gabapentin (70.98 ± 14.73 µg/paw; 10.95 ± 3.23 mg/kg po). The combinations produced their antinociceptive effects without motor impairment in the rotarod test indicating synergistic interactions with a good side effect profile.

Effects of chronic solvent abuse exposure on umami taste perception.

Inhalant abuse constitutes an important public health problem in Mexico that is more prevalent among children and adolescents. Commercial products that are abused are complex mixtures of solvents containing mainly toluene, in association with other solvents like benzene and xylene. Epidemiological evidence indicates that chronic solvent abuse exposure can cause loss of appetite among other unwanted effects. The mechanisms by which loss of appetite is produced are unknown. It is a matter of interest to determine if loss of appetite is related to changes in taste perception. One of the basic flavors detected by the taste system is umami taste (monosodium glutamate) and it has been proposed that glutamatergic receptors can play an important role in umami taste transduction and perception. It is unknown however, if chronic solvent abuse exposure can induce alterations in umami taste perception. The purpose of this work was to determine if chronic solvent exposure in rats causes alterations in glutamate solution consumption. Rats were exposed to solvents (6000 ppm) in a static chamber for 2 months, as follows: a toluene group, a benzene group, a xylene group and a control group. During the treatment, glutamate solution (120 mM) consumption, food intake and rat weights were measured. The results show that glutamate solution intake was increased in rats chronically exposed to solvents, with differences in consumption patterns between solvents. In addition, chronically exposed animals had a lower weight increase compared with unexposed rats. These data suggest that solvent inhalation originates feeding behavior alteration in rats.