Spinal NMDA NR1 subunit expression following transient TNBS colitis

Area of Science:

• Neuroscience
• Pain Research
• Gastroenterology

Background:

• N-methyl-D-aspartic acid (NMDA) receptors are implicated in visceral and somatic hypersensitivity following inflammation or injury.
• Transient trinitrobenzene sulfonic acid (TNBS)-induced colitis can lead to persistent hypersensitivity in a subset of rats.
• Understanding the role of NMDA NR1 receptor subunits in the spinal cord is crucial for explaining chronic pain states.

Purpose of the Study:

• To investigate the role of NMDA NR1 receptor expression in the spinal cord of rats exhibiting persistent hypersensitivity after TNBS-induced colitis.
• To compare spinal cord NMDA NR1 receptor expression in hypersensitive rats with that of recovered and control rats.
• To test the hypothesis that NMDA NR1 subunit expression mediates hypersensitivity following transient TNBS colitis.

Main Methods:

• Male Sprague-Dawley rats were administered intracolonic TNBS or saline.
• Nociceptive visceral and somatic pain testing was performed 16 weeks post-colitis resolution.
• Spinal cords (T10-L1; L4-S1) were analyzed using 2D polyacrylamide gel electrophoresis and immunohistocytochemistry for NMDA receptor expression.

Main Results:

• Hypersensitive rats uniquely expressed NMDA NR1 splice variants NR1(011) and NR1(111), in addition to NR1(001).
• Recovered and control rats only expressed the NR1(001) subunit.
• Immunohistochemistry revealed increased expression of NMDA NR1-N1, C1, and C2-plus subunits in spinal cord laminae I and II of hypersensitive rats.

Conclusions:

• Selective increases in NMDA NR1 splice variants are observed in rats with persistent hypersensitivity following TNBS colitis.
• These findings suggest NMDA NR1 receptor variants are critical for neuronal plasticity and central sensitization, maintaining hypersensitivity.
• Recombination of NR1 splice variants may be a key mechanism sustaining hypersensitivity after colitis resolution.