Pain is an unpleasant experience and effects daily routine negatively. Although there are various drugs, many of them are not entirely successful in relieving
pain, since
pain modulation is a complex process involving numerous mediators and receptors. Therefore, it is a rational approach to identify the factors involved in the complex process and develop new agents that act on these
pain producing mechanisms. In this respect, the involvement of the
imidazoline receptors in
pain modulation has drawn attention in recent years. In this review, it is aimed to focus on the
imidazoline receptors and their
ligands which contribute to the
pain modulation. It is demonstrated that imidazoline-2 (I2) receptors are steady new
drug targets for
analgesics. Even if the mechanism of I2 receptor is not well known in the modulation of
pain, it is known that it plays a role in tonic and
chronic pain but not in acute phasic
pain. Moreover, the I2 receptor
ligands increase the
analgesic effects of
opioids in both acute and
chronic pain and prevent the development of
opioid tolerance. So, they are valuable for the
chronic pain treatment and also therapeutic coadjuvants in the management of chronic
pain with
opiate drugs due to the attenuation of
opioid tolerance and addiction. Thus, the use of the
ligands which bind to the
imidazoline receptors is an effective strategy for relieving
pain. This educational forum exhibits the role of
imidazoline receptors and
ligands in
pain process by utilizing experimental studies.