The aim of the present study was to evaluate the central antinociceptive effects of eugenol after intraperitoneal administration. Experiments were carried out using male Sprague-Dawley rats. Subcutaneous injection of 5% formalin-induced nociceptive behavioral responses was used as the pain model. Subcutaneous injection of 5% formalin significantly produced nociceptive responses by increasing the licking time during nociceptive behavior. Subsequent intraperitoneal injection of 100 mg/kg of eugenol led to a significant decrease in the licking time. However, low dose of eugenol (50 mg/kg) did not affect the nociceptive behavioral responses produced by subcutaneous injection of formalin. Intrathecal injection of 30 μg of naloxone, an opioid receptor antagonist, significantly blocked antinociceptive effects produced by intraperitoneal injection of eugenol. Neither intrathecal injection of methysergide (30 μg), a serotonin receptor antagonist nor phentolamine (30 μg), an α-adrenergic receptor antagonist influenced antinociceptive effects of eugenol, as compared to the vehicle treatment. These results suggest that central opioid pathway participates in mediating the antinociceptive effects of eugenol.

Opioid receptors have been pharmacologically classified as µ, δ, κ and ε. We have recently reported that the antinociceptive effect of morphine (a µ-opioid receptor agonist), but not that of β-endorphin (a novel µ/ε-opioid receptor agonist), is attenuated by whole body irradiation (WBI). It is unclear at present whether WBI has differential effects on the antinociceptive effects of µ-, δ-, κ- and ε-opioid receptor agonists. In our current experiments, male ICR mice were exposed to WBI (5Gy) from a 60 Co gamma-source and the antinociceptive effects of opioid receptor agonists were assessed two hours later using the hot water (52℃) tail-immersion test. Morphine and D-Ala2,N-Me-Phe4,Gly-ol-enkephalin (DAMGO), [D-Pen2-D-Pen5]enkephalin (DPDPE), trans-3,4-Dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]¬benzeneacetamide (U50,488H), and β-endorphin were tested as agonists for µ, δ, κ, and ε-opioid receptors, respectively. WBI significantly attenuated the antinociceptive effects of morphine and DAMGO, but increased those of β-endorphin. The antinociceptive effects of DPDPE and U50,488H were not affected by WBI. In addition, to more preciously understand the differential effects of WBI on µ- and ε¬opioid receptor agonists, we assessed pretreatment effects of β-funaltrexamine (β-FNA, a µ-opioid receptor antagonist) or β-endorphin1-27 (β-EP1-27, an ε-opioid receptor antagonist), and found that pretreatment with β-FNA significantly attenuated the antinociceptive effects of morphine and β endorphin by WBI. significantly reversed the β-EP1-27 attenuation of morphine by WBI and significantly attenuated the increased effects of β-endorphin by WBI. The results demonstrate differential sensitivities of opioid receptors to WBI, especially for µ- and ε-opioid receptors.