Novel analgesic effects of melanin-concentrating hormone on persistent neuropathic and inflammatory pain in mice

Abstract

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 significantly earlier in both inflammatory and neuropathic pain. To examine its pharmacological properties, MCH was administered intranasally into mice, and results indicated that MCH treatment significantly 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 effects 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 effects induced by MCH. This is the first study to suggest novel analgesic actions of MCH, which holds great promise for the application of MCH in the therapy of pain-related diseases.

VGAT and VGLUT2 expression in MCH and orexin neurons in double transgenic reporter mice

“…Overall, our approach utilizing transgenic mice facilitates future studies that hope to identify and target potential GABA or glutamate neurons in the brain. Results from this study help us to better understand the role of these neurotransmitters and the role of neuropeptides on sleep/wake regulation, as well as other physiological processes including feeding, motor regulation, motivation regulation and pain modulation ( Zhang et al, 2013 ; Diniz and Bittencourt, 2017 ; Razavi and Hosseinzadeh, 2017 ; Jang et al, 2018 )…”

Identification of the Hub Genes Related to Nerve Injury-Induced Neuropathic Pain

“…After identification of the NP-associated genes, we performed enrichment analysis and found that these genes were predominantly enriched in some biological functions like hormone secretion and transport, potassium ion transport, humoral immune response, negative regulation of immune system process, while these functions have been proven to be involved in NP occurrence and development (Jaggi et al, 2015;Jang et al, 2018;Wang et al, 2018). Additionally, cAMP signaling pathway and ECM-receptor interaction are two signaling pathways that have been confirmed to be implicated with multiple functions in regulation of NP (Zhou et al, 2017;Yan et al, 2018;Yan et al, 2019), and our study observed that the genes we identified were activated in these two pathways as well.…”

Acupuncture Improves Comorbid Cognitive Impairments Induced by Neuropathic Pain in Mice

“…The electronic von Frey test (IITC, Woodland Hills, CA, United States) was conducted (Jang et al, 2018) to evaluate the mechanical allodynia. This test was performed before surgery and treatment (Base and 0 day), respectively, and was also conducted at 3, 7, 14, 21, and 28 days after 2 h of acupuncture and amitriptyline treatment (AM 11:00–PM 06:00).…”

“…Immunofluorescence was conducted (Jang et al, 2018) to measure the expression of NR2B and GluR1 in neuron cells in the PFC. Primary antibodies raised against NeuN (mouse, 1:500, MAB377; Chemicon International, Inc., Temecula, CA, United States), GFAP (mouse, 1:500, 14-9892-82; Thermo Fisher Scientific, San Diego, CA, United States), Iba-1 (mouse, 1:500, MABN92; Merck Millipore), NR2B (rabbit, 1:500, 06-600; Merck Millipore), and GluR1 (rabbit, 1:1000, #8084; Cell Signaling Technology) were diluted in 1 × PBST supplemented with 0.1% BSA.…”