Caenorhabditis elegans as a model to explore the genetic underpinnings of human pain-related processes: cannabinoid and opioid neuropharmacology as an example.

Caenorhabditis elegans has many traits that make it a valuable model for human neurobiology, including the study of pain-related processes. In particular, its genetic tractability can help uncover novel genetic factors involved in pain-related signal transduction. This can be beneficial for studying pain medications, such as cannabinoids and opioids. Here, we review how the pain-related impacts of cannabinoids/opioids have been assessed using behavioural assays (e.g., measuring feeding, locomotion, and nociception). Reviewed studies identified genetic factors responsible for both cannabinoid (e.g., endocannabinoid receptor npr-19) and opioid (e.g., opioid receptor npr-17) signalling, which were in turn used to characterize neurotransmission (e.g., monoaminergic, neuropeptidergic, and Hedgehog signalling) and complex modulators (e.g., TRP channels involved in cannabinoid signalling) contributing to cannabinoid/opioid signalling. Additionally, studies using these models were able to discover novel genetic components, including frpr-13 (orthologous to human GRP139), involved in opioid sensitivity, and ptr-25 (orthologous to human PTCHD1), involved in opioid tolerance. The pathways highlighted in this review represent clear paths for further investigation of the genetic mechanisms underlying individual differences in pain sensitivity, pain relief, and drug tolerance. Overall, this review demonstrates the value of C. elegans as a model for uncovering the genetic underpinnings of pain and its management.