The Role of the Subnucleus Reticularis Dorsalis (SRD) in Pain Modulation: A Literature Review.

The subnucleus reticularis dorsalis (SRD), also known as the dorsal reticular nucleus (DRt) or dorsal medullary reticular nucleus (MdD), which resides at the caudal end of the medulla, plays a pivotal role in regulating pain perception. Despite extensive research efforts to unravel its mechanisms, the operational intricacies of SRD remain poorly understood. Advances in experimental methodologies such as brain imaging and chemogenetics have facilitated deeper investigations into the involvement of SRD in various pain disorders. This comprehensive review aims to analyze 36 years (1989-2024) of preclinical research highlighting the critical role of SRD in diffuse noxious inhibitory control (DNIC), also known as conditioned pain modulation (CPM) in humans, and its interconnected neural circuits. Moreover, this review explores the neural circuits related to SRD, including locus coeruleus (LC)-SRD, parabrachial nucleus (PBN)-SRD, rostroventromedial medulla (RVM)-ventrolateral medulla (VLM)-SRD, anterior cingulate cortex (ACC)-SRD, medial medullary reticular formation (mMRF)-SRD, and dorsal striatum (DS)-SRD. Their activation also plays a significant role in analgesia. The pivotal roles of neurotransmitters such as μ-opioid receptor (MOR), noradrenaline, and metabotropic glutamate receptor 7 (mGluR7) in modulating SRD responsiveness to pain stimuli are also discussed, as are the influences of SRD on different pain types. This review identified promising avenues for innovative analgesic treatments by shedding light on potential therapeutic strategies targeting SRD.