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Since 1995, patients who suffer from severe acute and chronic pain have been prescribed opioid drugs to relieve their pain. Nevertheless, patients soon find they need to up their dose as they build a tolerance to the drugs. This, coupled with aversive withdrawal symptoms such as nausea and heightened pain sensitivity when not on their medication, contribute to the addictive nature and dangerous of overdose with these drugs. In addition, opioids can also elicit unexpected development of hyperalgesia, or an increase in sensitivity to normally noxious and also to nonnoxious stimuli, resulting in enhancement of pain. Therefore, it needs ongoing strategies for non-opioid pain drug discovery and development.
GPCRs are the largest class of sensory proteins and are crucial therapeutic targets in the pathways to pain. Pseudounipolar primary sensory neurons of dorsal root, vagal ganglia and trigeminal, also known as pruritoceptors and nociceptors, are the first cells in these pathways. The peripheral endings of these neurons are equipped with GPCRs which sense structurally diverse stimulants and inhibitors of neuronal activity. Second-order spinal neurons also express GPCRs for transmitters released from the central endings of primary sensory neurons and from other spinal neurons. Second-order neurons integrate signals and transmit pain to the brain. During disease, there are remarkable changes in the levels and types of GPCRs that are expressed by primary sensory neurons and their targets, which further indicate the dynamic nature of this system.
Although it is well established that some GPCRs can robustly internalize in sensory neurons, the importance of this process to pain transmission is unknown, and whether targeting GPCRs in endosomes is an effective therapeutic approach remains to be investigated. Creative Biogene can offer the largest commercial portfolio of GPCR assay solutions for pain and addiction research areas. Select targets are shown - view more GPCR targets.
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