Introduction: Melissa Officinalis (MO) overgrows in different parts of Iran. In
previous studies, ethanol extract of aerial parts (leaf & stem) of MO showed anti-
nconvulsant and sedative effects in rats. This study was designed to evaluate anti-
nociceptive effects in different doses of aqueous decoction extracts of MO and the
role of opioid receptors in rats.
Methods: In this experimental study, 63 male mice (weighing 25-30g) in Tail
Flick model were examined. Different doses of extract (5, 10, 25, 50 mg/kg IP-
MO) were injected to the separate groups and saline (10ml/kg-IP) was injected
intrapeditoneal in control group. In four groups the role of opioid receptors
(Naloxone 2mg.kg) was designed to evaluate anti-nociceptive effects in the
aqueous decoction extracts of MO (5mg/kg) and 25 minutes after the injection the
anti-nociceptive effect was evaluated. Analysis of variance was used to analysis
the data.
Results: The results showed that average time of Tail Flick had significant
difference in two groups (P<0.0001) but the test groups had no significant
difference in different doses. Based on the results, naloxone caused reduction in
antinociceptive effects of 5 mg/kg Melissa Officinalis dose (P<0.0001).
Conclusion: It is concluded that the aqueous extract of MO has anti-nociceptive
activity which is not dose related, and is probably related to opioid receptors.
Determination of other receptors which may have anti-nociceptive activity needs
further investigation.

The present study examined the antinociceptive effect of the ethanolic extract from Melissa officinalis L. and of the rosmarinic acid in chemical behavioral models of nociception and investigates some of the mechanisms underlying this effect. The extract (3-1000 mg/kg), given orally (p.o.) 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with ID50 value of 241.9 mg/kg. In the formalin test, the extract (30-1000 mg/kg, p.o.) also caused significant inhibition of both, the early (neurogenic pain) and the late (inflammatory pain), phases of formalin-induced licking. The extract (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of glutamate-induced pain, with ID50 value of 198.5 mg/kg. Furthermore, the rosmarinic acid (0.3-3 mg/kg), given p.o. 1 h prior, produced dose-related inhibition of glutamate-induced pain, with ID50 value of 2.64 mg/kg. The antinociception caused by the extract (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with atropine (1 mg/kg), mecamylamine (2 mg/kg) or L-arginine (40 mg/kg). In contrast, the extract (100 mg/kg, p.o.) antinociception was not affected by i.p. treatment with naloxone (1 mg/kg) or D-arginine (40 mg/kg). It was also not associated with non-specific effects, such as muscle relaxation or sedation. Collectively, the present results suggest that the extract produced dose-related antinociception in several models of chemical pain through mechanisms that involved cholinergic systems (i.e. through muscarinic and nicotinic acetylcholine receptors) and the L-arginine-nitric oxide pathway. In addition, the rosmarinic acid contained in this plant appears to contribute for the antinociceptive property of the extract. Moreover, the antinociceptive action demonstrated in the present study supports, at least partly, the ethnomedical uses of this plant.