Pharmacogenomics of neuropathic pain

Abstract

Variation in pain sensitivity and analgesic drug response is well recognized among individuals. Pharmacogenomics hypothesis dictates that a patient’s response to a drug or development of adverse drug effects may depend on variation in genetic profile, in particular, the different alleles for the same gene that an individual carries. A review of the role of genetic variations in determining the receptor sensitivity and modulation of pain, response to analgesics drugs and their interactions are presented in this article. It is already known that genomic variations affect the pharmacokinetic and pharmacodynamic properties of various analgesic drugs. Genes related to the expression of mu-opioid receptor, ATP- binding cassette B1 (ABCB1), catechol-O-Methyl Transferase (COMT), Cytochrome P450 enzymes have been widely studied and show some promise in determining the drug response in individuals. Some recent studies on sodium channel mutations (SCN9A, SCN11A) have been implicated in congenital insensitivity to pain. Voltage gated ion channels such as sodium, calcium and potassium channels are being targeted for development of novel analgesics. Based on the available research, the clinical implementation of pharmacogenomics for personalized pain medicine is still in its infancy, but is promising. These are opening further opportunities for development of newer analgesics targeting pain receptors and ion channels.

Pregabalin for neuropathic pain in primary care settings: recommendations for dosing and titration

“…The 'low and slow' approach recognizes that patients with NeP are heterogeneous in terms of their optimal therapeutic dose. Response to drugs is influenced by multiple individual differences (e.g., in pathophysiology, renal function, genetics, age, level of sensitivity to pain [62]), all of which can complicate identifying the optimal effective dose and tolerability profile. The 'low and slow' approach increases the therapeutic dose more slowly than recommended in the prescribing information [27] (up to the maximum recommended doses), because some patients need more careful titration to manage potential side effects.…”