Prospective Study About Clinical and Pharmacogenetic Safety of Opioid Use for Chronic Pain

Pain continues to be a major problem in patients with cancer, affecting 25% to 30% of patients with recently diagnosed cancers. The incidence of pain in advanced stages of cancer approaches 70% to 80%. There are a number of reasons that patients with cancer experience chronic pain either related to the disease itself or to its treatment. Cancer can spread by metastasis or direct invasion, and 90% of patients with metastasis to osseous structures report pain. Patients with cancer can have neuropathic pain due to direct compression of nerves or plexus or spinal cord involvement. Inadequate treatment and undertreatment are associated with increased pain scores, decreased functional ability, and increased depression and anxiety. Opioid administration though proven to be effective still meets with resistance from both healthcare operators, who are seldom willing to prescribe these drugs, and patients, who tend to not take them because of many false beliefs still related to opioids. It is well demonstrated by the literature that opioids are effective in controlling both acute and chronic pain of nociceptive and/or neuropathic origin. Switching type of opioid and/or administration routes (e.g., from oral to neuraxial) is also known to be an important factor in long-term treatment: appropriate conversion tables elucidating drug equipotence and different potency in base of administration route for the different opioids currently available have therefore been devised and validated in the clinical setting. There have been several attempts to define guidelines for treatment protocols and even recent meta-analyses indicate that morphine should remain the gold standard. However, a general consensus is still lacking, as opioid management depends not only on the type and cause of pain, but also on the patient's history, the pain characteristics and genetic patterns. Which, if any, is the best opioid, in relation with previous characters, to start systemic treatment remains therefore debated. The different effects that different opioids have on spinal cord sensitization as a result of continuous peripheral nociceptive stimulus in long term administration have also been partially investigated. Current pharmacogenetic publications analyze the pharmacokinetic behavior of opioids in short-term administration, but studies are still lacking on how the pharmacokinetics and analgesic effect vary after repeated administrations of opioids, especially through direct comparison with clinical response. Genetic studies showed differences in the results of opioid treatment related to the variability of the genes that have a role in the pharmacodynamic and pharmacokinetics of opioids. Regardless these studies, the literature has not yet investigated how quantitative and qualitative variability of gene products can influence the efficacy or the toxicity of a specific opioid treatment.