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Prolonged noxious stimulation increases periaqueductal gray NMDA mRNA expression: a hybridization study using two
1Department of Anatomy, King Saud University, College of Medicine, Abha, Saudi Arabia.
Abstract:
The density and distribution of N-methyl-D-aspartate receptor (NMDAR1) mRNA expression in the rat midbrain periaqueductal gray (PAG) following exposure to unilateral peripheral inflammation or chronic constrictive injury (CCI) as models for chronic peripheral nociception were examined using in situ hybridization technique. The NMDAR1 hybridization signal intensities increased significantly in the ventrolateral areas of the caudal and middle thirds of the PAG after 3 days of Complete Freund's Adjuvant (CFA) injection. Likewise, rats subjected to CCI showed significant increase in hybridization signal intensities in comparison to sham-operated animals in both the ipsi- and contra-lateral ventrolateral quadrants of the caudal and middle thirds of the PAG. In the caudal dorsal raphe, the CFA and the CCI treated animals showed a significant increase in signal hybridization compared to control and sham-operated groups while the rostral dorsal raphe showed no significant changes in either CCI or CFA treated groups. In contrast, there was no significant change in signal intensity of NMDAR1 mRNA in the dorsal subdivisions of the PAG following either CCI or CFA treatment. These results demonstrate significant bilateral increase in NMDAR1 mRNA expression in the ventrolateral areas of the caudal and middle thirds of the PAG and the caudal one half of the dorsal raphe following chronic nociception. The up-regulation phenomenon may constitute a reactive mechanism against chronic neuropathic pain in the PAG.
Insights
Chronic pain models show increased N-methyl-D-aspartate receptor (NMDAR1) mRNA in the periaqueductal gray (PAG). This upregulation in specific PAG regions may be a response to chronic neuropathic pain.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Chronic pain, including neuropathic pain, involves complex changes in the central nervous system.
- The N-methyl-D-aspartate receptor (NMDAR1) is crucial for synaptic plasticity and pain signaling.
- The periaqueductal gray (PAG) plays a significant role in pain modulation.
Purpose of the Study:
- To investigate the expression patterns of NMDAR1 mRNA in the rat PAG under conditions of chronic peripheral nociception.
- To determine if peripheral inflammation or chronic constrictive injury (CCI) alters NMDAR1 mRNA levels in specific PAG subregions.
Main Methods:
- In situ hybridization technique was employed to quantify NMDAR1 mRNA expression.
- Rats were subjected to Complete Freund's Adjuvant (CFA) injection or CCI as models of chronic pain.
- NMDAR1 signal intensities were analyzed in different PAG subdivisions, including ventrolateral and dorsal areas, and the dorsal raphe nucleus.
Main Results:
- Significant increases in NMDAR1 mRNA hybridization signal were observed in the ventrolateral PAG (caudal and middle thirds) following both CFA and CCI.
- Both ipsilateral and contralateral ventrolateral quadrants of the caudal and middle PAG showed increased NMDAR1 expression after CCI.
- The caudal dorsal raphe nucleus exhibited increased NMDAR1 mRNA expression in CFA and CCI groups, while the rostral dorsal raphe and dorsal PAG subdivisions showed no significant changes.
Conclusions:
- Chronic nociception induces a significant bilateral upregulation of NMDAR1 mRNA in the ventrolateral PAG and caudal dorsal raphe.
- This observed NMDAR1 mRNA upregulation in the PAG may represent a compensatory mechanism involved in managing chronic neuropathic pain.
- Findings highlight the involvement of specific PAG circuits in the central processing of chronic pain states.
