Scientific REPORts | (2018) 8:707 | DOI:10.1038/s41598-018-19145-z
Novel analgesic eects of
on persistent neuropathic and
inammatory pain in mice
, Ji-Yeun Park
, Ju-Young Oh
, Sun-Jeong Bae
, Hyunchul Jang
, Jongpil Kim
& Hi-Joon Park
The melanin-concentrating hormone (MCH) is a peptidergic neuromodulator synthesized by neurons
in the lateral hypothalamus and zona incerta. MCHergic neurons project throughout the central
nervous system, indicating the involvements of many physiological functions, but the role in pain
has yet to be determined. In this study, we found that pMCH
mice showed lower baseline pain
thresholds to mechanical and thermal stimuli than did pMCH
mice, and the time to reach the
maximum hyperalgesic response was also signicantly earlier in both inammatory and neuropathic
pain. To examine its pharmacological properties, MCH was administered intranasally into mice, and
results indicated that MCH treatment signicantly increased mechanical and thermal pain thresholds
in both pain models. Antagonist challenges with naltrexone (opioid receptor antagonist) and AM251
(cannabinoid 1 receptor antagonist) reversed the analgesic eects of MCH in both pain models,
suggesting the involvement of opioid and cannabinoid systems. MCH treatment also increased the
expression and activation of CB1R in the medial prefrontal cortex and dorsolateral- and ventrolateral
periaqueductal grey. The MCH1R antagonist abolished the eects induced by MCH. This is the rst study
to suggest novel analgesic actions of MCH, which holds great promise for the application of MCH in the
therapy of pain-related diseases.
Pain is a universal experience from birth until the end of life. More than 80% of individuals seeking medical care
cite pain as the reason for doing so, citing the signicant impact that pain has had on their quality of life. Various
pharmacological treatments, such as opiates, are used to relieve chronic pain
. However, these treatments oen
cannot meet patients’ needs due to unsatisfactory ecacy and adverse side eects
. erefore, new analgesic
agents without adverse eects are required.
Melanin-concentrating hormone (MCH) is a cyclic 19-amino acid neuropeptide synthesized by neurons in the
lateral hypothalamus and zona incerta
. e MCH system was originally implicated in energy homeostasis, such
as feeding and metabolic activity, but is also involved in the regulation of sleep
, and reward
biological functions of MCH are mediated by two G-protein coupled receptors, the MCH 1 receptor (MCH1R)
and the MCH 2 receptor (MCH2R)
. MCH1R is widely distributed throughout the rodent
, whereas MCH2Rs are present in humans but not rodents
. MCHergic neurons project throughout the
rodent central nervous system (CNS) to areas such as the somatosensory cortex, isocortex, caudate putamen,
Acupuncture and Meridian Science Research Center, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemun-gu,
Seoul, 02447, Republic of Korea.
Department of Korean Medical Science, Graduate School of Korean Medicine,
Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu, Seoul, 02447, Republic of Korea.
BK21 PLUS Korean
Medicine Science Center, College of Korean Medicine, Kyung Hee University, 26 Kyungheedae-ro, Dongdaemoon-gu,
Seoul, 02447, Republic of Korea.
College of Korean Medicine, Daejeon University, 62 Daehak-ro, Dong-gu,
Daejeon, 34520, Republic of Korea.
Mibyeong Research Center, Korean Institute of Oriental Medicine, 1672
Yuseong-daero, Yuseong-gu, Daejeon, 34054, Republic of Korea.
Department of Biomedical Sciences, Center for
Creative Biomedical Scientists at Chonnam National University, Gwangju, 61469, Republic of Korea.
Biomedical Engineering, Dongguk University, Dongguk-Ro 32, Goyang, 10326, Republic of Korea. Correspondence
and requests for materials should be addressed to S.J. (email: email@example.com) or J.K. (email: jpkim153@
dongguk.edu) or H.-J.P. (email: firstname.lastname@example.org)
Received: 21 March 2017
Accepted: 22 December 2017
Published: xx xx xxxx