The use of opioids for the treatment of chronic pain has increased dramatically over the past decade [32,33]. However, as indicated above, the responsiveness to opioids in chronic pain patients may vary depending on individual differences but also on the type of pain [34,35]. For instance, a number of studies have evidenced that neuropathic pain patients are insensitive to opioids. The pharmacodynamic response to a given opioid depends on the nature of the receptor to which the opioid binds and its affinity for the receptor. During recent years, a wide range of candidate genes relevant to pain has been highlighted [8] and these genes are associated with a variety of molecules involved in pain processing, including neurotransmitters and their receptors and transporters, metabolic enzymes, ion channels, intracellular enzymes and second messengers. Minor changes in allelic variability, like SNPs, may affect the functionality of the encoded protein, resulting in an alteration of the protein activity or in the transcription rate leading to lower or higher amounts of the relevant protein [36]. An example of this is the decreased μ-opioid receptor mRNA and protein expression in human brain tissue in the presence of the OPRM1 118 G variant [37].
