19 Harley St, London, W1G 9QJ, UK

Peripheral antinociceptive effects of MC4 receptor antagonists in a rat model of neuropathic pain – a biochemical and behavioral study

Recent studies have suggested that melanocortins contribute to the generation and/or maintenance of pathological pain. Experimental evidence indicates a primary role for melanocortin 4 (MC4) receptors in pathological pain. In a previous study, we described the presence of MC4 receptor transcripts in the dorsal root ganglia (DRG). This finding prompted us to investigate the peripheral antinociceptive effects of MC4 receptor antagonists. In addition, we assess the expression of MC4 receptors in the spinal cord and the DRG of rats subjected to neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Injection of the MC4 receptor antagonists Asp3-Lys8- Ac-Nle-Asp-His-D-Nal(2′)-Arg-Trp-Lys-NH(2) (SHU9119) and Mpr1-Cys8-Mpr-Glu-His-(D-Nal)-Arg-Trp-Gly-Cys-Pro-Pro-Lys-Asp-NH(2) (JKC-363) into the ipsilateral paw resulted in a significant and dose-dependent alleviation of mechanical allodynia (assayed by the von Frey test) and thermal hyperalgesia (assayed by the Hargreaves test). Compared to naive control animals, immunohistochemistry revealed a 40% and 22% increase in MC4 receptor-immunoreactivity (IR) in the dorsal horn of the spinal cord ipsilateral to the injury at 3 and 14 days after CCI, respectively. Similarly, in the ipsilateral L4-L5 DRG, a 21.1% enhancement in MC4 receptor-IR was seen 3 days after CCI, as well as a 40.5% increase 14 days after CCI. Together, painful neuropathy resulted in the up-regulation of MC4 receptors in the spinal and peripheral nociceptive pathways. This up-regulation of MC4 receptors promotes the pronociceptive action of their endogenous ligands. Therefore, a block of the MC4 receptors results in the antagonism of neuropathic pain and such treatment could be beneficial therapeutically for individuals with chronic neuropathic pain

Keywords : administration & dosage,Analgesics,Animals,antagonists & inhibitors,beta-MSH,Disease Models,Animal,Dose-Response Relationship,Drug,drug therapy,Ganglia,Spinal,genetics,Hyperalgesia,Immunohistochemistry,injuries,Ligands,Male,Melanocyte-Stimulating Hormones,metabolism,Neuralgia,Pain,Peptides,Peptides,Cyclic,pharmacology,physiopathology,Rats,Rats,Wistar,Receptor,Melanocortin,Type 4,Sciatic Nerve,Spinal Cord,Time Factors,Up-Regulation,, Antinociceptive,Effects,Mc4,Receptor, botox london cost

Date of Publication : 2009 Nov

Authors : Starowicz K;Mousa SA;Obara I;Chocyk A;Przewlocki R;Wedzony K;Machelska H;Przewlocka B;

Organisation : Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Krakow, Poland

Journal of Publication : Pharmacol Rep

Pubmed Link : https://www.ncbi.nlm.nih.gov/pubmed/20081244

The London Spine Unit : Harley Street UK. Specialists in Cutting Edge Technologies for Spinal Surgery

Make an Appointment 

Trustpilot Reviews
Doctify Reviews
Top Doctor Reviews

Peripheral antinociceptive effects of MC4 receptor antagonists in a rat model of neuropathic pain - a biochemical and behavioral study | Bac neck brace

What our patients say ...

Consultant Spine Surgeon
Consultant Spine Surgeon
Consultant Spine Surgeon

This surgical technique consists of a percutaneous approach for the treatment of small to medium size hernias of the intervertebral disc by laser energy. The main objective is to reduce the intradiscal pressure in the nucleus pulposus

Laser Disc Surgery can be performed under local anaesthetic as a day case at our centre on the prestigious Harley Street.
What is London spine unit and How it Works

The London Spine Unit was established in 2005 and has successfully treated over 5000 patients. All conditions are treated.

treatment of all spinal disorders

The London Spine Unit specialises in Minimally Invasive Treatments allowing rapid recovery and return to normal function

Trusted by patients worldwide

The London Spine Unit provides the highest quality care to all patients and has VIP services for those seeking exceptional services

If you have any emergency Doctor’s need, simply call our 24 hour emergency

Your personal case manager will ensure that you receive the best possible care.

Call Now 

+44 844 589 2020
+44 203 973 8810