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

•Toluene exposure enhanced formalin-induced acute and long-lasting nociception.•Alosetron reduced toluene pronociceptive effect on formalin-induced nociception.•m-CPBG further enhanced the effect of toluene on formalin-induced nociception.•Alosetron blocked m-CPBG pronociceptive effect on formalin-induced nociception.•Methiothepin did not affect toluene effect on formalin-induced nociception.

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 (6000 ppm) for 30 min enhanced 0.5% or 1% formalin-induced acute nociception and long-lasting secondary allodynia and hyperalgesia. In contrast, exposition to toluene for 30 min 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 (100 nmol) 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 (10 nmol) blocked the pronociceptive effects of m-CPBG (300 nmol) on 0.5% formalin-induced acute and long-lasting hypersensitivity in rats exposed to toluene. Alosetron (at 10 nmol) did not modify formalin-induced nociceptive behaviors. Finally, local peripheral pre-treatment with methiothepin (non-selective 5-HT receptor antagonist, 1.5 nmol), 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.