Neuroprotective effect of agmatine in mouse spinal cord injury model: Modulation by imidazoline receptors

Spinal cord injury often results in disability or loss of movement and sensation below the site of injury.At present, few treatments for spinal cord injury are available, however with less significant functional improvement.Agmatine, an endogenous amine, exists in mammalian brain and has been proposed as a novel neurotransmitter/neuromodulator. [1]The distribution of agmatine-containing neurons is concentrated in regions of the brain that subserve visceral and neuroendocrine control, processing of emotions, pain perception, cognition, and memory.Agmatine has been implicated in several biological processes such as neuroprotection, [2] antinociception, [3] convulsions, [4] stress, [5] depression, [6] and anxiety. [7]It is interesting to note that agmatine also dose-dependently attenuates neuropathic pain in rodents. [8]11] Further, agmatine also attenuated the pain associated with diabetic neuropathy. [3,11,12]Its peripheral administration enhanced morphine analgesia dose-dependently in neuropathic rats. [13]Moreover, systemically administered agmatine significantly reduces the mechanical and thermal hyperalgesia as well as allodynia in neuropathic mice caused by spinal cord injury.Agmatine binds to several target receptors such as imidazoline, N-methyl-D-aspartate (NMDA), nicotinic cholinergic, α 2 -adrenergic, serotonergic receptors, and inhibits nitric oxide synthase.Agmatine is co-localized with imidazoline receptor in several brain areas.Moreover, several pharmacological effects of agmatine are mediated through imidazoline receptors.The role of imidazoline receptor in nociception is fairly well established.Imidazoline binding sites have currently attracted attention in nociception as well as drug addiction. [14]oreover, the brain structures involved in the drug abuse and pain perception including hypothalamus, hippocampus, and amygdala are rich in imidazoline binding sites and its endogenous ligands.