Specifically, chronic pain, broadly categorized as non-cancer and cancer pain, is notoriously challenging to treat, and its poor management resulting from a “one-size-fits-all” strategy, remains a significant cause of misery with huge socioeconomic costs.
The need for new molecular targets to design more effective pain treatments options is evident
Over the past decade, improved understanding of the genetic underpinning of many diseases have resulted in the explosion of targeted therapies that have paved the way to personalized, and precision medicine.
pain stimulus from the same origin can produce wide differences in different individuals with respect to
- how much pain is felt,
- how long it lasts, and
- the quality of response to treatment
Indeed, evidence is accumulating for “pain-enhancing” and “pain-reducing” genes, as well as genes that may confer effectiveness of a pain drug to one person but intolerance or toxicity to another person.
Furthermore, cytochrome P450 2D6 (CYP2D6) genotype has been identified as having important clinical relevance for response to opioid analgesics that depend on CYP2D6 metabolism for bio-activation
Variation in the CYP2D6 genotype may determine how well individuals respond to opioids analgesic
For example, poor metabolizers (PMs) have lower concentrations of active metabolites of codeine (morphine), tramadol (O-desmethyltramadol), oxycodone (oxymorphone) and hydrocodone (hydromorphone), compared to extensive metabolizers (EMs).
Consequently, PMs may fail to derive pain relief from these opioids compared to EMs. Intermediate metabolizers (IMs) are also expected to have reduced analgesic response based on their significant reduction in enzyme activity, while individuals with ultrarapid metabolizer (UM) phenotype may have toxic concentrations of active opioid metabolites, with reports of life-threatening toxicity and death.
Recent efforts focused on improved understanding of the genotype–phenotype associations of migraine pain has important implications for precision pain management, by determining the clinical utility of gene targeting, identifying clinically relevant biomarkers, and paves a path for safer personalized pain management.
In fact, dysregulated expression of circulating microRNAs (miRNAs) in bodily fluids is being explored as a non-invasive clinical biomarker for a variety of disorders including chronic pain.
Given that the current approach to chronic pain management is largely by trial and error,
the need for precision chronic pain medicine is immense.
“The exciting thing about our study is that it provides proof-of-principle that, using genomics and atomic-level modeling, we could match a specific pain medicine to a particular person’s DNA, and thus, successfully predict that [a specific] medication would reduce pain in [a specific] person.
There is evidence to support an association of the TWIK-related spinal cord potassium (K+) channel (TRESK) gene, and the methylene tetrahydrofolate reductase (MTHFR) gene in migraine pain.
Clinical application of gene-targeted precision pain medicine is still a long way ahead.
While the concept of precision medicine for chronic pain is supported by the Federal Government, few clinical studies have been conducted. Much of the necessary methodology remains to be developed.
Funding, time and commitment for complex genetic research, pain biomarker studies and analysis of clinically relevant findings are all required