Chasing the Holy Grail of Pain: Pharmacogenomics and Personalized Pain Management

The influence of genetic variation on a drug response may one day allow for optimized management of pain. Personalized medicine strategies will potentially allow healthcare providers to uniquely address cytochrome P450 genes regarding basic metabolism‑‑as well as other genes encoding receptors for cytokines, growth factors, hormones, and neurotransmitters‑‑and proteins involved with carriers, enzymes, ion channels, transcription factors, and transporters. Pharmaceutical researchers will take us beyond large population treatments with a “large brush,” and deliver more precisely tailored individualized therapies addressing the causative molecular biology of pain. Already, according to a recent edition of the pharmaceutical information newsletter the Pink Sheet, attempts have been made to create focused anti-NGF (nerve growth factor) therapies, blockers of sodium channel NAV1.7, P2X3 selective sodium and calcium channel modulators, with a long view toward preventing chronic pain, rather than just trying to manage it.

Clifford Woolf, MD, PhD, director of the F. M. Kirby Neurobiology Center at Children’s Hospital Boston and a professor of neurobiology at Harvard Medical School, describes a series of different types of pain. His research has shown that different forms of pain represent heterogeneous neurological syndromes with differing neural pathways likely to require different treatment methods. Woolf predicts that we will need to phenotype pain and then select medications accordingly within the next decade.

At the IASP meeting in Milan in August 2012, there was active and lively discussion regarding the use of anti-multiple sclerosis therapies to reverse and/or prevent the development of opioid tolerance and opioid-induced hyperalgesia. The underlying theory advanced was to view opioids, plant-derived alkaloids, as sensitizing and inflaming the central nervous system. Rather than rotate from molecule to molecule as we do now, the best future treatment might be the alteration of the nervous system’s immune response.

Our current challenge involves translating from promising animal models to human pain. For humans, pain is so much more than just a raw, adverse sensation. Humans have placebo responses, experience pain within the context of complicated lives, and have their lives influenced by many external factors.

Personalized medicine is the future

Nevertheless, managing pain is big business. According to IMS Health, as quoted in The Pink Sheet for February 25, 2013, analgesics sales for 2009 were $20 billion in the US, and $34 billion worldwide. Opioids and statins are the most prescribed medications in the US. Five million Americans seek treatment for their chronic pain in the US annually.

What would all this mean one day for the field of pain medicine? Would this take us in radically new treatment directions? Would we move from our current reliance upon oral medications, anesthetic and other interventions, rehabilitative models, and all of the other things now done to an entirely different approach for managing pain? How would we integrate newer methods within existing payment systems, with their reluctance to pay for “experimental” therapies until they are well established and proven?

It is currently not clear how to respond to the idea of personalized medicine for pain control beyond watching the direction of research, continuing to learn more about the molecular biology of pain, and viewing the field of pain management as continuously evolving. The future of pain management may one day come down to the results of a buccal swab or a blood test.

Precisely knowing what is causing one person’s pain may change our treatment from population-based to highly patient-centric. This will potentially lead to highly effective treatment that may be more expensive due to the need for individualization. As we await the full implementation of the Affordable Care Act we barely have answers about questions of access and basic coverage. Exactly where personalized pain medicine will fit into our future healthcare system still awaits us.