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Updated: Apr 5, 2026
Electrophysiological Methods to Assess Peripheral Pain Block in an Anesthetized Rat
Published on: November 21, 2025
[Activation of spinal MrgC receptors inhibits hyperalgesia in rats]
Jian-Ping Jiang1, Yan Fu2,3, Fen-Juan Hu2
1College of Life Sciences, Fujian Normal University, Fujian Key Laboratory of Developmental and Neuro Biology, Fuzhou 350117, China. jjp@fjnu.edu.cn.
Abstract:
This study was aimed to investigate the mechanisms of the modulation effect of activation of spinal Mas-related gene C (MrgC) receptors on hyperalgesia induced by intraplantar (i.pl.) injection of (Tyr6)-γ2-MSH-6-12 (MSH) or complete Freund's adjuvant (CFA). Paw withdrawal latency test and immunohistochemistry were used to observe the effect of intrathecal (i.t.) administration of MSH or BAM8-22, two selective agonists of MrgC receptor, in hyperalgesia in rats. The results showed that i.t. administration of MSH inhibited acute hyperalgesic response induced by i.pl. application of MSH, while did not change thermal nociceptive threshold in naïve rats. The i.t. administration of MSH also attenuated CFA-induced inflammatory hyperalgesia. However, i.t. administration of the μ-opioid receptor (MOR) antagonist CTAP blocked the induction of delayed anti-hyperalgesia by MSH. The i.t. injection of BAM8-22 at a dose of 30 nmol evidently reduced the number of CFA-evoked nitric oxide synthase (NOS)-positive neurons and the expression of calcitonin gene-related peptide (CGRP)-immunoreactivity positive nerve fibers at L3-L5 segments of the spinal cord. These results suggest that the activation of MrgC receptor in CFA-induced inflammation reduces inflammatory hyperalgesia through inactivation of NOS neurons and down-regulation of CGRP expressions, and generates delayed but long-lasting anti-nociception through the endogenous activation of MOR via indirect mechanisms. Agonists for MrgC receptors may, therefore, represent a new class of antihyperalgesics for treating inflammatory pain because of the highly specific expression of their targets.
Insights
Activation of spinal Mas-related gene C (MrgC) receptors can reduce inflammatory pain. This involves inhibiting nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP) pathways, potentially offering new antihyperalgesic treatments.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Inflammatory pain is a significant clinical challenge.
- Mas-related gene C (MrgC) receptors are implicated in pain modulation.
- Understanding MrgC receptor mechanisms is crucial for developing novel analgesics.
Purpose of the Study:
- To investigate the role of spinal MrgC receptor activation in hyperalgesia.
- To elucidate the mechanisms underlying MrgC receptor-mediated antinociception.
- To assess the potential of MrgC receptor agonists as antihyperalgesic agents.
Main Methods:
- Intraplantar (i.pl.) injection of (Tyr6)-γ2-MSH-6-12 (MSH) or complete Freund's adjuvant (CFA) to induce hyperalgesia in rats.
- Intrathecal (i.t.) administration of MSH or BAM8-22 (selective MrgC receptor agonists).
- Paw withdrawal latency tests and immunohistochemistry to evaluate nociception and neuronal changes.
Main Results:
- Intrathecal MSH inhibited acute MSH-induced hyperalgesia and attenuated CFA-induced inflammatory hyperalgesia.
- The μ-opioid receptor (MOR) antagonist CTAP blocked MSH-induced delayed ant-hyperalgesia.
- BAM8-22 reduced nitric oxide synthase (NOS)-positive neurons and calcitonin gene-related peptide (CGRP) expression in the spinal cord.
Conclusions:
- Spinal MrgC receptor activation reduces inflammatory hyperalgesia via NOS and CGRP pathways.
- Delayed antinociception involves endogenous MOR activation through indirect mechanisms.
- MrgC receptor agonists show promise as a new class of antihyperalgesics for inflammatory pain.
