Pain is an unsightly sensory and impenetrableexperience that it caused by intense or damaging stimuli and regulates by the consolidation of complexactions modulated by central factors (10m1). Many parts of brain such as the nucleus ofperiaqueductal grey (PAG) have important role in pain modulation (1mR).Ghrelin, a 28-amino acid gastric acylated peptide, is as anendogenous ligand for the orphan growth hormone secretagogue receptor 1?(GHS-R1?). There is two type of ghrelin receptors, 1? and 1?, but only GHS-R1ahas the ability to activating signal transduction downstream of the receptor(). Ghrelin is originally secreted of the stomach but also it secreted ofseveral peripheral and central nervous systems such as hypothalamus andhypophysis 9. Ghrelin receptors have been seen in different areas of centralnervous system, especially in hypothalamus, pons, and medulla, as well as inareas that are responsible for controlling the pain transmission10, Thereforelocalization of ghrelin and its receptors demonstrate that ghrelin has a keyrole in antinociceptive system (16 ? 1).
(D-lys)-GHRP-6 is the selective antagonist forGHS-R1? (20 ? 17) and it seemsantagonizes the antinociceptive effect of ghrelin. Ghrelin has also inhibitory effect on inflammatory pain throughinterfering with the central opioid system (11, 12). Preceding researchers havedemonstrated that ghrelin has excitatory effects on neurons of the ventromedialarcuate nucleus (33 ?1), where neurons are containing endogenousopioids (2 ?1), and the involvement of these opioids in inflammatory pain alignment has beenwell demonstrated (1–4). Insome research it has been observed neurons containing ghrelin, innervate otherpeptidergic systems such as neurons containing pro-opiomelanocortin (POMC) (6 ?1). POMC-derived ?-endorphin has a key role in theantinociveptive system (38 ?1). And in other research It has been shownthat, ACTH-ir drived from POMC (4m21) and enkeohalin neurons (m21) wereidentified in ARC terminal fields in the PAG.
The focus of some previous studies was on the antinociceptive effect of ghrelin. Accordingto previous research, it has been reported that ghrelin inhibits theinflammatory pain induced by carrageenan in rats via interaction with thecentral opioid system (29 ? 17). Other researcheshave demonstrated that ghrelin palliates chronic neuropatic pain (8 ? 13 ?17) and prohibits cisaplatin-inducedmechanical hyperalgesia and cachexia (6 ?17).However in this study, the effects of ghrelin injection in the arcuate nucleus ofhypothalamus or cerebroventricular in inflammatory pain have been investigatedin the formalin test. In addition, levels of ?-endorphine, and met-enkephalinare measured in rat periaqueductal gray area with HPLC method.