Textbook of Personalized Medicine - Second Edition [2015]

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The molecular mechanisms that underlie pain vary among individuals over time and
among different types of pain to produce wide inter-individual variations in pain
perception and response. Pharmacogenetics has the potential to improve patient
therapy and care, and it is hoped that it will individualize drug treatment to a greater
extent in the near future (Stamer and Stuber 2007 ).
To address these issues, basic science research is beginning to identify the allelic
variants that underlie such antinociceptive variability using a multiplicity of animal
models, and powerful genetic approaches are being exploited to accelerate this pro-
cess. Although the vast majority of these studies have focused on the pharmacoge-
netics of opioids, owing to their prominent status as analgesics, the number of
pharmacotherapies refl ecting genetically-based variability is rapidly expanding. In
addition, analogous studies have been undertaken in humans, as a small but grow-
ing number of clinical trials have begun to evaluate prospectively the existence,
often not the origin, of interindividual differences in analgesic drug response.
Presentation of the spectrum of individual responses and associated prediction
intervals in clinical trials can convey clinically meaningful information regarding
the impact of a pain treatment on health-related quality of life. Individual responder
analyses are proposed for use in clinical trials to better detect analgesic activity
across patient groups and within sub-groups, and to identify molecular-genetic
mechanisms that contribute to individual variation.
Studies have shown that people with red hair need 20 % more general anesthesia
than blonds and brunettes. Redheads are also more sensitive to thermal pain and are
more resistant to the effects of local anesthesia. Variants of the melanocortin-1
receptor (MC1R) gene, which produces melanin, play a role. While blond, brown
and black-haired people produce melanin, those with red hair have a mutation of
this receptor that produces a different coloring called pheomelanin, which results in
freckles, fair skin and red hair. Approximately 5 % of whites are estimated to have
these characteristics. Although the relationship between MC1R and pain sensitivity
is not proven, MC1R receptors have been found in the brain and some of them are
known to infl uence pain sensitivity.

Personalized

Pain

Management

Pharmacogenetics

of analgesics

Pharmacogenomics

of pain syndromes

Pharmaco-

diagnostics of pain

Mechanism-based

drug discovery

Selection of best

treatment (s) for patient

Targeted delivery of

therapy for pain

Clinical diagnosis of

type of pain & cause

Conditioned pain

modulation status

of patient

© Jain PharmaBiotech

Fig. 12.5 Essential components of personalized management of pain

Personalized Management of Pain