PAG of studies have been shown that ghrelin and

PAG has an important role
in descending pain control pathway (21mr). The brain stem structures send
descending impulse to the spinal cord and inhibit the transmission of
nociception signals in the spinal cord (22mr). met-enkephalin and
beta-endorphin have an important role as endogenous opioids in antinociceptive

A number of studies have been shown that ghrelin and its receptor,
GHS-R1?, were expressed in diverse brain areas such as the hypothalamus (11,
42, 46 m1). The location of ghrelin and its receptors indicative their role in
modulation pain systems (16m1). Ghrelin has stimulating effects on neurons of
ventromedial ARC (33m1) where endogenous opioid containing neurons are found
(2m1). Ghrelin has a positive effect on release or synthesis of opioid peptides
and activate pro- opiomelanocortin (POMC) neurons which have anti-nociceptive
effects (9m17). Recent studies have indicated, ghrelin have a role in control
of pain and centrally or peripherally ghrelin administration, prevent from
progress of hyperalgesia induced by intraplantar carrageenan injection in the
rat (35m1), the ghrelin receptor in this process is not GHS-R1? (36m1). Some
research demonstrated ghrelin modulate inhibitory transmission in spinal cord
dorsal horn and stop cisplatin persuade mechanical hyperalgesia and cachexia
(11,13,42 m1). Ghrelin increases inhibitory neurotransmission in spinal cord
dorsal horn in mouse via reaction with GHS-R1? (42 m1). Ghrelin decrease the
inflammatory pain in rat via reaction with central opioid system (46m1).

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There is some case, have been shown the ?-endorphin neurons
expedition from ARH to nucleus accumbens and lateral septum then projectcting
to the PAG, nucleus raphe dorsalis and the locus coreleus (5m1). The beta-endorphinergic
nerve terminals in PAG, probably indicated the involvement of the ARC/PAG endorphinergic
pathway (m15) and ?-endorphin was neurotransmitter involve in accombens to PAG
(m15).Previous study indicated that PAG and raphe nucleus are rich in
opiocortin –ir (3 m21) and also opioid receptors (3’m21). ACTH fiber of ARC
projects to PAG and raphe nucleus (m21). There are neurons immunoreactive to
substance p, neurotensin and encephalin in ARC that end up at the PAG (m21). Microinjection
of morphine into the nucleus accumbens blocked by met- encephalin antibodies or
naloxone injection, this indicated, there is a descending pain modulatory
pathway from nucleus accombens to PAG and endogenous opioids specially met-
encephalin were as neurotransmitter (6 m1).