We are pleased to introduce the collection Frontiers in Pain Research – Highlights in Cancer Pain 2021/22. This collection will welcome and showcase a selection of high impact articles authored by leaders in the field. The work presented here highlights the broad diversity of research performed across the Cancer Pain section, and aims to put a spotlight on the main areas of interest. This collection aims to further support Frontiers’ strong community by shining a spotlight on our authors' highly impactful research.

Central Michigan University

University of Milano-Bicocca

Frontiers in Pain Research

Cancer Pain

Highlights in Cancer Pain 2021/22

Oxaliplatin, which is widely used in treating cancers such as colorectal cancer, frequently causes peripheral neuropathy. It not only significantly reduces the patient's quality of life due to physical distress but may also result in a change or discontinuation of cancer treatment. Oxaliplatin-induced peripheral neuropathy (OIPN) is classified as acute or chronic depending on the onset time of side effects; however, the prevention and treatment of OIPN has not been established. As these peripheral neuropathies are side effects that occur due to treatment, the administration of effective prophylaxis can effectively prevent their onset. Although transient relief of symptoms such as pain and numbness enable the continuation of cancer treatment, it may result in the worsening of peripheral neuropathy. Thus, understanding the pathological mechanisms of OIPN and finding better preventative measures are important. This review focuses on animal models to address these issues, clarifies the pathological mechanisms of OIPN, and summarizes various approaches to solving OIPN, including targets for preventing OIPN.

Oxaliplatin, which is widely used in treating cancers such as colorectal cancer, frequently causes peripheral neuropathy. It not only significantly reduces the patient&apos;s quality of life due to physical distress but may also result in a change or discontinuation of cancer treatment. Oxaliplatin-induced peripheral neuropathy (OIPN) is classified as acute or chronic depending on the onset time of side effects; however, the prevention and treatment of OIPN has not been established. As these peripheral neuropathies are side effects that occur due to treatment, the administration of effective prophylaxis can effectively prevent their onset. Although transient relief of symptoms such as pain and numbness enable the continuation of cancer treatment, it may result in the worsening of peripheral neuropathy. Thus, understanding the pathological mechanisms of OIPN and finding better preventative measures are important. This review focuses on animal models to address these issues, clarifies the pathological mechanisms of OIPN, and summarizes various approaches to solving OIPN, including targets for preventing OIPN.

Pathological Mechanisms and Preventive Strategies of Oxaliplatin-Induced Peripheral Neuropathy

A clinical conundrum can occur when a patient with active opioid use disorder (OUD) or at elevated risk for the condition presents with cancer and related painful symptoms. Despite earlier beliefs that cancer patients were relatively unaffected by opioid misuse, it appears that cancer patients have similar risks as the general population for OUD but are more likely to need and take opioids. Treating such patients requires an individualized approach, informed consent, and a shared decision-making model. Tools exist to help stratify patients for risk of OUD. While improved clinician education in pain control is needed, patients too need to be better informed about the risks and benefits of opioids. Patients may fear pain more than OUD, but opioids are not always the most effective pain reliever for a given patient and some patients do not tolerate or want to take opioids. The association of OUD with mental health disorders (dual diagnosis) can also complicate delivery of care as patients with mental health issues may be less adherent to treatment and may use opioids for “chemical coping” as much as for pain control.

A clinical conundrum can occur when a patient with active opioid use disorder (OUD) or at elevated risk for the condition presents with cancer and related painful symptoms. Despite earlier beliefs that cancer patients were relatively unaffected by opioid misuse, it appears that cancer patients have similar risks as the general population for OUD but are more likely to need and take opioids. Treating such patients requires an individualized approach, informed consent, and a shared decision-making model. Tools exist to help stratify patients for risk of OUD. While improved clinician education in pain control is needed, patients too need to be better informed about the risks and benefits of opioids. Patients may fear pain more than OUD, but opioids are not always the most effective pain reliever for a given patient and some patients do not tolerate or want to take opioids. The association of OUD with mental health disorders (dual diagnosis) can also complicate delivery of care as patients with mental health issues may be less adherent to treatment and may use opioids for &#x201c;chemical coping&#x201d; as much as for pain control.

Opioid Therapy in Cancer Patients and Survivors at Risk of Addiction, Misuse or Complex Dependency

Pain is a common symptom in cancer patients, restricts daily life activities and reduces survival time. Identification of sociodemographic, medical and psychological correlates of pain among cancer patients in Germany could help identify subgroups most in need of pain management. In this multicenter, epidemiologic cross-sectional study, we assessed pain prevalence and severity, quality of life (QoL) and psychological distress in a sample of 3,745 cancer patients across all tumor entities. In total, 37.9% patients suffered from cancer-related pain and 56.1% suffered from non-specific pain. Younger, female, less educated and unemployed patients reported pain more frequently and more severe pain (p < 0.001). Pain was associated with distress, depression, anxiety, QoL, tumor stage (p < 0.001), and time since diagnosis (p = 0.012). Pain assessment and pain management should be a routine part of cancer treatment and cancer survivorship care plans.

Pain is a common symptom in cancer patients, restricts daily life activities and reduces survival time. Identification of sociodemographic, medical and psychological correlates of pain among cancer patients in Germany could help identify subgroups most in need of pain management. In this multicenter, epidemiologic cross-sectional study, we assessed pain prevalence and severity, quality of life (QoL) and psychological distress in a sample of 3,745 cancer patients across all tumor entities. In total, 37.9% patients suffered from cancer-related pain and 56.1% suffered from non-specific pain. Younger, female, less educated and unemployed patients reported pain more frequently and more severe pain (p &lt; 0.001). Pain was associated with distress, depression, anxiety, QoL, tumor stage (p &lt; 0.001), and time since diagnosis (p = 0.012). Pain assessment and pain management should be a routine part of cancer treatment and cancer survivorship care plans.

Prevalence and Severity of Pain in Cancer Patients in Germany

Background: Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain.Methods: EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists.Results: A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors.Conclusions: This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 may play a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.

Background: Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain.Methods: EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists.Results: A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors.Conclusions: This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 may play a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.