Opioid Use in Cancer Pain Management: Navigating the Line Between Relief and Addiction

Abstract

The use of opioids for cancer-related pain is essential but poses significant challenges due to the risk of misuse and the development of opioid use disorder (OUD). This review takes a multidisciplinary perspective based on the current scientific literature to analyze the pharmacological mechanisms, classification, and therapeutic roles of opioids in oncology. Key risk factors for opioid misuse-including psychiatric comorbidities, prior substance use, and insufficient clinical monitoring-are discussed in conjunction with validated tools for pain assessment and international guidelines. The review emphasizes the importance of integrating toxicological, pharmacological, physiological, and public health perspectives to promote rational opioid use. Pharmacogenetic variability is explored as a determinant of treatment response and addiction risk, underscoring the value of personalized medicine. Evidence-based strategies such as early screening, psychosocial interventions, and the use of buprenorphine-naloxone are presented as effective measures for managing OUD in cancer patients. Ultimately, this work advocates for safe, patient-centered opioid prescribing practices that ensure effective pain relief without compromising safety or quality of life.

Keywords: addiction prevention; cancer-related pain; opioid use disorder; opioids; pain management; personalized medicine; pharmacogenetics.

Figure 1

Key factors of cancer-related pain. The figure summarizes the main aspects involved in the assessment and understanding of cancer-related pain (CRP), including etiology, anatomical location, evaluation through the Numeric Rating Scale (NRS), prevalence across different stages of treatment, and patient-specific factors. This multidimensional approach supports a comprehensive and personalized pain management strategy in oncology. Created in BioRender. Ruiz de Porras, V. (2025). https://BioRender.com/1aov67t.

Figure 2

Cellular mechanism of action of opioid receptors. Binding of an opioid agonist to the µ-opioid receptor activates Gi/o protein signaling, leading to inhibition of adenylyl cyclase and a subsequent decrease in intracellular cyclic adenosine monophosphate (cAMP) levels and protein kinase A (PKA) activity. This results in reduced phosphorylation of intracellular proteins. Concurrently, opioid receptor activation inhibits voltage-gated calcium channels (reducing excitatory neurotransmitter release) and opens potassium channels, causing membrane hyperpolarization. These combined effects lead to reduced neuronal excitability and diminished synaptic transmission. +: activation; −: inhibition. Created in BioRender. Ruiz de Porras, V. (2025). https://BioRender.com/bx6zmb5.

Figure 3

Neurobiological mechanisms of opioid addiction. Opioids bind to µ-opioid receptors in the mesocorticolimbic system (MCLS), leading to inhibition (Ͱ) of GABAergic neurons in the ventral tegmental area (VTA). This disinhibits dopaminergic neurons, causing increased (↑) dopamine release in the nucleus accumbens, which promotes euphoria and positive reinforcement. With chronic opioid use (--->), neuroadaptations occur via activation of the amygdala and the hypothalamic–pituitary–adrenal (HPA) axis, resulting in the release of corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. This stress response, along with the release of dynorphin, contributes to negative emotional states such as dysphoria, anxiety, and irritability, reinforcing drug-seeking behavior through negative reinforcement. Created in BioRender. Ruiz de Porras, V. (2025). https://BioRender.com/9vft0z4.