Dorsal horn NMDA receptor function is changed after peripheral inflammation.

Area of Science:

• Neuroscience
• Pain Research
• Pharmacology

Background:

• N-methyl-D-aspartic acid (NMDA) receptors play a role in pain sensitization.
• The phenomenon of 'wind-up' in neurons is a key aspect of pain processing.
• Carrageenan-induced inflammation is a common model for studying inflammatory pain.

Purpose of the Study:

• To investigate the effect of NMDA receptor antagonism on neuronal wind-up following acute inflammation.
• To compare the efficacy of NMDA receptor antagonists in sensitized versus non-sensitized neurons.
• To explore underlying mechanisms of wind-up in dorsal horn neurons.

Main Methods:

• Electrophysiological recordings from single wide dynamic range (WDR) neurons in rats.
• Administration of D, L-2-amino-5-phosphonopentanoic acid (AP5), an NMDA receptor antagonist.
• Induction of carrageenan inflammation to model sensitization.
• Application of wind-up inducing stimulus trains and nociceptive input.

Main Results:

• AP5 caused stronger inhibition of wind-up in inflamed WDR neurons compared to control neurons.
• Inflammation (2.5 h) induced functional changes in NMDA receptor activity.
• In non-sensitized neurons, AP5 reduced evoked responses but significantly increased wind-up.
• NMDA receptor antagonists showed increased effects in sensitized states, similar to long-term potentiation.

Conclusions:

• Acute inflammation sensitizes neurons, leading to altered NMDA receptor function and increased wind-up.
• NMDA receptor-dependent mechanisms may be less critical for wind-up in non-sensitized dorsal horn neurons.
• Sensitized and non-sensitized neurons exhibit differential responses to NMDA receptor-active drugs, highlighting the complexity of pain modulation.