More than half of patients affected by cancer experience pain of moderate-to-severe intensity, often in multiple sites, and of different etiologies and underlying mechanisms. The heterogeneity of pain mechanisms is expressed with the fluctuating nature of cancer pain intensity and clinical characteristics. Traditional ways of classifying pain in the cancer population include distinguishing pain etiology, clinical characteristics related to pain and the patient, pathophysiology, and the use of already validated classification systems. Concepts like breakthrough, nociceptive, neuropathic, and mixed pain are very important in the assessment of pain in this population of patients. When dealing with patients affected by cancer pain it is also very important to be familiar to the characteristics of specific pain syndromes that are usually encountered. In this article we review methods presently applied for classifying cancer pain highlighting the importance of an accurate clinical evaluation in providing adequate analgesia to patients.

Neuropathic pain can be defined as pain related to abnormal somatosensory processing in either the peripheral or central nervous system. In this review article, with neuropathic cancer pain (NCP), we refer to pain due to nervous tissue lesions caused by the tumor or its metastases. Nervous tissue damage is the cause of cancer pain in approximately 40% of those experiencing cancer pain. Recognizing a neuropathic pathophysiology in these cases may be difficult and requires specific criteria that are not homogenously applied in clinical practice. The management of this type of pain can be challenging, requiring the use of specific non-opioid adjuvant drugs. The majority of the criteria for NCP diagnosis and management have been based mainly on results from the noncancer population, risking the failure of addressing the specific needs of this population of patients. In this review, we summarize current management options available for NCP and provide some insights on new promising treatments.

Neuropathic cancer pain (NcP) is associated with worse treatment responses and specific therapy indications, but a standardized clinical diagnosis of NcP is still lacking. This is a prospective observational study on outpatients with cancer, comparing different clinical approaches with NcP evaluation. A three-step assessment of NcP was performed using DN4 (cutoff of 4), palliative care physician Clinical Impression, including etiology and pain syndrome identification, and Retrospective Clinical Classification by a board of specialists with the IASP Neuropathic Pain Special Interest Group criteria. Neuropathic cancer pain classification was specifically referred to pain directly due to cancer. Three hundred fifty patients were assessed, and NcP prevalence was 20% (95% confidence interval [CI] 15.9%-24.6%), 36.9%, (95% CI 31.6%-42.1%), and 28.6% (95% CI 23.8%-33.9%) according to DN4, Clinical Impression, and Retrospective Clinical Classification, respectively. Cohen's kappa concordance coefficient between DN4 and Retrospective Clinical Classification was 0.57 (95% CI 0.47-0.67), indicating moderate concordance. Higher percentages of discordance were found for specific pain syndromes such as pain due to deep soft tissue infiltration and pain associated with tenesmus. Disagreement among clinicians accounted also for different NcP diagnoses and highlighted lack of homogeneous clinical criteria. Rigorous application of etiological and syndrome diagnosis to explain pain cause, associated with standardized diagnostic criteria and assessment of pain characteristics, that is also specific for the cancer pain condition could improve clinical classification of NcP.

Objectives During the COVID-19 pandemic, telemedicine (TM) emerged as an important mean to reduce risks of transmission, yet delivering the necessary care to patients. Our aim was to evaluate feasibility, characteristics and satisfaction for a TM service based on phone/video consultations for patients with cancer attending an outpatient palliative care clinic during COVID-19 pandemics. Methods A longitudinal observational study was conducted from April to December 2020. Consecutive patients were screened for video consultations feasibility. Either patients or their caregivers received video/phone consultations registering reason and intervention performed. Those contacted at least twice were eligible for experience of care assessment. Results Video consultations were feasible in 282 of 572 screened patients (49%, 95% CI 45% to 52%); 112 patients among the 572 had at least two phone/video consultations and 12 of them had one or more video consultations. Consultations were carried out with patients (56%), caregivers (30%) or both (14%). 63% of the consultations were requested by the patients/caregivers. Reasons for consultation included uncontrolled (66%) or new symptom onset (20%), therapy clarifications (37%) and updates on diagnostic tests (28%). Most interventions were therapy modifications (70%) and appointments’ rescheduling (51%). 49 patients and 19 caregivers were interviewed, reporting good care experience (average of 1–5 satisfaction score of 3.9 and 4.2, respectively). The majority (83% and 84%) declared they would use TM after the pandemics. Conclusions Although feasibility is still limited for some patients, TM can be a satisfactory alternative to in-person visits for palliative care patients in need of limiting access to the hospital.

Background: Pain is a prevalent symptom in patients with advanced cancer. Recognition of prognostic factors associated with pain intensity, could help provide better assessment, leading to better pain management. Aim: identifying prognostic factors which could guide improvements on cancer pain classification. Design: a prospective observational study on chronic cancer pain, exploring the association between average mean pain intensity during a 28 days study follow-up and patients’ clinical and pain-related characteristics, including pain syndromes. To evaluate these associations, a mixed model was built. Setting/participants: Patients attending a Palliative Care and Pain Outpatient Clinic from May 2015 to June 2019 were screened. Patients with moderate to severe cancer pain who were already receiving or needed treatment with third step WHO ladder opioids were enrolled in the study. Data from 342 patients with at least one follow-up visit were analyzed. Results: Pain intensity decreased significantly for all patients during time ( p < 0.001). Age, sex, emotional distress, pain duration and neuropathic pain presence evaluated by the Douleur Neuropathique 4 Questions (DN4) questionnaire were not significantly associated to pain intensity. Breakthrough/episodic pain was associated with higher pain intensity during follow-up ( p < 0.001). The diagnosis of pain syndrome was overall significantly associated with mean pain intensity during follow-up ( p = 0.016). Particularly, the concurrent presence of visceral and soft ( p = 0.026) or soft and nervous tissue pain ( p = 0.043) were significantly related to worse outcome, whereas pain due to only soft tissue damage with better outcome ( p = 0.032). Conclusions: The recognition of specific pain syndromes may help to better classify cancer pain.

Background: Opioids in step III of the WHO analgesic ladder are the standard of care for treating cancer pain. However, a significant minority of patients do not benefit from therapy. Genetics might play a role in predisposing patients to a good or poor response to opioids. Here, we investigated this issue by conducting a genome‐wide association study (GWAS).Methods: We genotyped 2057 European advanced cancer patients treated with morphine, buprenorphine, fentanyl and oxycodone. We carried out a whole‐genome regression model (using REGENIE software) between genotypes and the opioid response phenotype, defined as a numerical score measuring patient pain intensity.Results: The GWAS identified five non‐coding variants on chromosome 20 with a p‐value <5.0 × 10⁻⁸. For all of them, the minor allele was associated with lower pain intensity. These variants were intronic to the PCMTD2 gene and were 200 kbp downstream of OPRL1, the opioid related nociceptin receptor 1. Notably according to the eQTLGen database, these variants act as expression quantitative trait loci, modulating the expression mainly of PCMTD2 but also of OPRL1. Variants in the same chromosomal region were recently reported to be significantly associated with pain intensity in a GWAS conducted in subjects with different chronic pain conditions.Conclusions: Our results support the role of genetics in the opioid response in advanced cancer patients. Further functional analyses are needed to understand the biological mechanism underlying the observed association and lead to the development of individualized pain treatment plans, ultimately improving the quality of life for cancer patients.Significance Statement: This genome‐wide association study on European advanced cancer patients treated with opioids identifies novel regulatory variants on chromosome 20 (near PCMTD2 and OPRL1 genes) associated with pain intensity. These findings enhance our understanding of the genetic basis of opioid response, suggesting new potential markers for opioid efficacy. The study is a significant advancement in pharmacogenomics, providing a robust dataset and new insights into the genetic factors influencing pain intensity, which could lead to personalized cancer pain management.