Opioid genetics: the key to personalized pain control?

Abstract

There are now several strong opioids available to choose from for the relief of moderate to severe pain. On a population level, there is no difference in terms of analgesic efficacy or adverse reactions between these drugs; however, on an individual level there is marked variation in response to a given opioid. The genetic influences to this variation are complex, and although current research has shown some promising results, these have not been replicated across larger studies and as such the ultimate aim of personalized prescribing remains elusive. If personalized prescribing could be achieved this would have a major impact at an individual level to facilitate safe, effective and rapid symptom control. This review presents some of the recent positive advances in opioid pharmacogenetic studies, focusing on associations between candidate genes and the three main elements of opioid response: analgesic, upper gastrointestinal and central adverse reactions.

Genetic Polymorphism of Cytokines as a Predictor of Phenotypic Development of Chronic Pain Syndrome in Cancer Patients

“…(21)(22)(23) These SNPs increase the risk of cancer development due to a higher level of TNF-α. (24) Currently, SNP 308G>A (rs1800629) of the TNF-α gene is known to predetermine a higher pain syndrome intensity and a lower response to opioids in lung cancer patients, (9,25) being associated with the syndrome of cancer cachexia and fatigue. The CC genotype (837 T>C, rs5275) of the TNF-α gene carriers with lung cancer have a lower risk of severe pain development as compared to carriers of SNP 308G>A (rs1800629) and 50 C>T (rs8904) of the NFKBIA-EX6 gene.…”

“…(7,8) Proinflammatory cytokines (TNF-α, IL-1, IFN-γ, and IL-6) and anti-inflammatory cytokines (IL-10, IL-4, and TNF-β) are known as markers of tissue damage. (9) IFN-γ is a key modulator of CB2 receptors. (7) Activation of CB2 receptors located in glial cells contributes to neuropathic pain.…”

“…Cytokines might participate in the proliferation and angiogenesis of cancer cells. (9) IL-1β, TNF-α and IL-6 are early cytokines synthesized in response to neuron damage and are potent COX-2 activators.…”

“…(7,11) In cases of cancer pain, cytokines promote pain sensitivity through direct cellular interaction or nociceptor activity modulation. (1,9) A total of 50 known cytokine ligands ensure their interaction with different cells of the organism. Ligands are conditionally subdivided into ССL, CXC, CX3С, and XC.…”

Splice variation of the mu-opioid receptor and its effect on the action of opioids

“…[1][2][3][4][5] In this review, we focus on the impact of splice variation of the mu-opioid receptor (MOR) on the clinical effect of opioids.…”