Oprd1-KO Mouse

Oprd1 encodes the delta-opioid receptor. This receptor has multiple functions, notably regulating reward pathways [1]. The gene is of biological importance as it contains over 2,000 verified genetic variants, with some having significant associations with human diseases, thus highlighting the value of genetic models for its study.

Nerve injury in male and female mice upregulates the transcription repressor REST in the dorsal root ganglion (DRG), which in turn downregulates the mRNA levels of Oprd1 [2,3]. Conditional knockout of full-length Rest in primary sensory neurons reduces nerve injury-induced pain hypersensitivity and rescues the reduction in Oprd1 expression, suggesting that REST-mediated repression of Oprd1 transcription in primary sensory neurons may contribute to neuropathic pain [2,3].

In conclusion, Oprd1, through its encoded delta-opioid receptor, plays a role in regulating reward pathways. Findings from the nerve injury-related mouse models indicate that Oprd1 may be involved in the development of neuropathic pain, providing insights into potential therapeutic targets for this condition.

References:

1. Crist, Richard C, Clarke, Toni-Kim. . OPRD1 Genetic Variation and Human Disease. In Handbook of experimental pharmacology, 247, 131-145. doi:10.1007/164_2016_112. https://pubmed.ncbi.nlm.nih.gov/28035534/

2. Subedi, Ashok, Tiwari, Aadhya, Etemad, Asieh Fashkache, Pan, Hui-Lin, Majumder, Sadhan. 2024. Nerve injury inhibits Oprd1 and Cnr1 transcription through REST in primary sensory neurons. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.02.17.579842. https://pubmed.ncbi.nlm.nih.gov/38585789/

3. Subedi, Ashok, Etemad, Asieh, Tiwari, Aadhya, Pan, Hui-Lin, Majumder, Sadhan. 2024. Nerve injury inhibits Oprd1 and Cnr1 transcription through REST in primary sensory neurons. In Scientific reports, 14, 26612. doi:10.1038/s41598-024-74487-1. https://pubmed.ncbi.nlm.nih.gov/39496614/