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Neuropathic pain in individuals with cancer remains a challenging clinical problem that requires advanced pharmacologic skills and a clear understanding of the molecular mechanisms that drive it.
At the 32nd Annual Congress of the Italian Society of Palliative Care, 3 experts outlined an updated framework that begins with basic biology and leads to the most appropriate therapeutic choice.
Fibre Reprogramming
Diego Maria Michele Fornasari, professor of pharmacology and director of the Postgraduate School of Specialization in Pharmacology and Clinical Toxicology at the University of Milan, Milan, Italy, outlined how a healthy nerve fibre becomes chronically hyperexcitable.
“The pathogenic mechanisms of pain, even though we experience hundreds of different pains, can be counted on the fingers of one hand,” he said.
In oncology, nerve injury caused by tumour compression, chemotherapy, or radiotherapy initiates a molecular cascade that reshapes the nerve fibre.
“The injured area is reprogrammed because the neuron attempts to regenerate, and to regenerate it must express proteins seen during embryonic life,” Fornasari said.
This process leads to the appearance of embryonic sodium channels (particularly Nav1.3), which impart abnormally high electrical activity to neurones.
The second mechanism involves the loss of a protective physiologic feature, namely, intermittent failure of signal conduction. Under normal conditions, occasional conduction failures reduce pain intensity. In neuropathic pain, overexpression of hyperpolarisation–activated cyclic nucleotide-gated channels, the same channels that govern sinoatrial node automaticity, makes the neuron hyperexcitable and unable to modulate transmission. The result is that “all stimuli reach the spinal cord and the central nervous system.”
Fornasari illustrated the concerns regarding pain in bone metastases. “The tumour cell is an intelligent cell, capable of producing substances that can interfere with nociceptive mechanisms,” he said.
He also highlighted the mechanisms of pain in patients with bone metastases. Prostate cancer cells that metastasised to the bone that produce tumour cells produce large amounts of nerve growth factor, which does not promote growth in adult neurones but causes hypertrophy and sprouting of nerve fibres. “Each of these ‘spikes’ is actually a neuropathic lesion of the fibre,” Fornasari explained, clarifying how this mechanism contributes to the often-devastating intensity of pain from bone metastases.
Diagnostic Precision
Francesca Dina Ricchini, oncologist and palliative care specialist working in the Palliative Care Unit at the National Cancer Institute in Milan, Italy, addressed the translation of molecular knowledge into clinical diagnosis. “It is very important to be able to translate these concepts into diagnostic tools,” she said.
Neuropathic involvement affects approximately 40% of individuals with cancer, with 20% presenting with pure neuropathic pain and another 20% with mixed pain.
Approximately 75% of cases are related to the disease itself, and the remainder are related to oncologic treatments. Despite its prevalence, neuropathic pain remains underdiagnosed, contributing to suboptimal analgesia and an impaired quality of life.
Screening tools such as PainDETECT, DN4, and the LANSS scale can support assessment, but Ricchini cautioned that “they are tools that can be used as aids but do not make a diagnosis on their own and have not been validated in oncology patients.”
She noted that quantitative sensory testing (QST) complements clinical judgement by quantifying sensory thresholds for thermal, mechanical, and pain stimuli, aiding in the identification of neuropathic pain mechanisms, particularly in oncology settings. QST can complement clinical judgement and diagnostic algorithms developed by the International Association for the Study of Pain to help clinicians systematically identify neuropathic components.
“The key is to start from symptoms, what the patient tells us,” Ricchini added.
However, bedside assessments remain essential. Simple tool needles, cotton, and the clinician’s thumb allow the evaluation of hyperalgesia, allodynia, and other neuropathic features of the affected area. With careful history taking and physical examination, clinicians can often reach an accurate diagnosis without complex testing.
Opioid Use
Sebastiano Mercadante, director of the Anesthesia & Intensive Care and Pain Relief and Supportive Care Unit in La Maddalena Cancer Center Palermo at the University of Palermo in Palermo, Italy, discussed opioid therapy in neuropathic pain. “Responsiveness to opioid drugs varies from patient to patient,” he said.
Opioids develop tolerance and have a ceiling effect that is driven by adverse events. Mercadante emphasised the need to “optimise their use” by staying within the therapeutic window where the benefits outweigh the harm.
Responsiveness depends on genetic polymorphisms affecting receptors and metabolism, pain patterns, age, sex, and psychological distress. “Those with the worst response are patients with significant psychological distress,” he noted.
The opioid escalation index helps to stratify patients. Slow escalation predicts a better prognosis, whereas rapid escalation should prompt specialist involvement and evaluation of factors such as delirium, anxiety, and depression in patients.
Drug Strategies
Switching opioids can be helpful when they become less effective. Mercadante explained that switching opioids “can facilitate receptor internalisation, excluding from continuous stimulation,” allowing “receptor refreshing” and allowing an overstimulated system to be cleared and restoring analgesia. Switching to methadone, when conducted by experienced clinicians, often yields substantial benefits for patients.
Fornasari clarified the mechanisms of action of gabapentinoids, which act on the alpha-2-delta subunit of calcium channels by restoring normal channel numbers rather than by closing them. This distinction is important because it is a slow mechanism that requires approximately 2 weeks for full effect, which is crucial information for clinicians who often discontinue treatment prematurely after a few days of treatment.
Antidepressants, including amitriptyline and serotonin-norepinephrine reuptake inhibitors such as duloxetine, strengthen descending inhibitory pathways by increasing serotonin and noradrenaline levels.
Fornasari also mentioned desvenlafaxine, the active metabolite of venlafaxine, which “has greater activity on descending noradrenergic pathways” and could be particularly useful when the predominant component is noradrenergic.
Topical Options
Capsaicin is an option for chemotherapy-induced peripheral neuropathy.
Chemotherapy-induced neuropathy, the expert explained, is related to the overexpression of transient receptor potential cation channel subfamily V member 1, also known as the capsaicin receptor. Topical capsaicin abnormally stimulates these receptors, causing a massive influx of calcium that “defunctionalises the fibre” for periods ranging from a week to 2 months.
Clinical Takeaways
Therefore, neuropathic pain, particularly in patients with cancer, requires a multimodal approach that begins with an understanding of the molecular mechanisms to develop personalised treatment options. As Fornasari concluded, “Often, a lack of knowledge of a drug’s mechanism of action leads to its inappropriate, and ultimately ineffective, use.” The challenge for clinicians is to translate this knowledge into tangible improvements for patients, remembering that each patient is unique and requires personalised care that goes beyond standardised protocols.
Clinicians aim to translate these insights into meaningful relief, recognising that each patient requires tailored care.
Practical Guidance
- Accurate diagnosis: Screening tools should only be used as support, and decisions should be on the basis of a detailed history and physical examination. In individuals with cancer, the interview always began with the patient’s account.
- Recognising negative prognostic factors: Neuropathic pain, incident pain, psychological distress, delirium, and unrealistic expectations indicate a more difficult course and require a more intensive approach.
- Opioids should be used wisely: Dose escalation should be monitored, rotation should be considered when needed, and psychological factors should be assessed throughout care. As experts have noted, clinicians should try at least 2 or 3 opioids and at least 2 routes of administration before considering invasive procedures.
- Integrating adjuvant medicines early: Gabapentin and other antidepressants are not third-line treatments for individuals with cancer. Adequately dosed for at least 2 weeks to allow therapeutic benefit.
- Consider topical options: In localised peripheral neuropathies, capsaicin can be a valid addition to treatment.
- Use of non-opioid medicines: Some individuals respond exceptionally well to anti-inflammatory agents, with effects that can match those of high morphine doses.
This story was translated from Univadis Italy, part of the this news organization Professional Network.
A version of this article appeared on Medscape.com.
Neuropathic pain in individuals with cancer remains a challenging clinical problem that requires advanced pharmacologic skills and a clear understanding of the molecular mechanisms that drive it.
At the 32nd Annual Congress of the Italian Society of Palliative Care, 3 experts outlined an updated framework that begins with basic biology and leads to the most appropriate therapeutic choice.
Fibre Reprogramming
Diego Maria Michele Fornasari, professor of pharmacology and director of the Postgraduate School of Specialization in Pharmacology and Clinical Toxicology at the University of Milan, Milan, Italy, outlined how a healthy nerve fibre becomes chronically hyperexcitable.
“The pathogenic mechanisms of pain, even though we experience hundreds of different pains, can be counted on the fingers of one hand,” he said.
In oncology, nerve injury caused by tumour compression, chemotherapy, or radiotherapy initiates a molecular cascade that reshapes the nerve fibre.
“The injured area is reprogrammed because the neuron attempts to regenerate, and to regenerate it must express proteins seen during embryonic life,” Fornasari said.
This process leads to the appearance of embryonic sodium channels (particularly Nav1.3), which impart abnormally high electrical activity to neurones.
The second mechanism involves the loss of a protective physiologic feature, namely, intermittent failure of signal conduction. Under normal conditions, occasional conduction failures reduce pain intensity. In neuropathic pain, overexpression of hyperpolarisation–activated cyclic nucleotide-gated channels, the same channels that govern sinoatrial node automaticity, makes the neuron hyperexcitable and unable to modulate transmission. The result is that “all stimuli reach the spinal cord and the central nervous system.”
Fornasari illustrated the concerns regarding pain in bone metastases. “The tumour cell is an intelligent cell, capable of producing substances that can interfere with nociceptive mechanisms,” he said.
He also highlighted the mechanisms of pain in patients with bone metastases. Prostate cancer cells that metastasised to the bone that produce tumour cells produce large amounts of nerve growth factor, which does not promote growth in adult neurones but causes hypertrophy and sprouting of nerve fibres. “Each of these ‘spikes’ is actually a neuropathic lesion of the fibre,” Fornasari explained, clarifying how this mechanism contributes to the often-devastating intensity of pain from bone metastases.
Diagnostic Precision
Francesca Dina Ricchini, oncologist and palliative care specialist working in the Palliative Care Unit at the National Cancer Institute in Milan, Italy, addressed the translation of molecular knowledge into clinical diagnosis. “It is very important to be able to translate these concepts into diagnostic tools,” she said.
Neuropathic involvement affects approximately 40% of individuals with cancer, with 20% presenting with pure neuropathic pain and another 20% with mixed pain.
Approximately 75% of cases are related to the disease itself, and the remainder are related to oncologic treatments. Despite its prevalence, neuropathic pain remains underdiagnosed, contributing to suboptimal analgesia and an impaired quality of life.
Screening tools such as PainDETECT, DN4, and the LANSS scale can support assessment, but Ricchini cautioned that “they are tools that can be used as aids but do not make a diagnosis on their own and have not been validated in oncology patients.”
She noted that quantitative sensory testing (QST) complements clinical judgement by quantifying sensory thresholds for thermal, mechanical, and pain stimuli, aiding in the identification of neuropathic pain mechanisms, particularly in oncology settings. QST can complement clinical judgement and diagnostic algorithms developed by the International Association for the Study of Pain to help clinicians systematically identify neuropathic components.
“The key is to start from symptoms, what the patient tells us,” Ricchini added.
However, bedside assessments remain essential. Simple tool needles, cotton, and the clinician’s thumb allow the evaluation of hyperalgesia, allodynia, and other neuropathic features of the affected area. With careful history taking and physical examination, clinicians can often reach an accurate diagnosis without complex testing.
Opioid Use
Sebastiano Mercadante, director of the Anesthesia & Intensive Care and Pain Relief and Supportive Care Unit in La Maddalena Cancer Center Palermo at the University of Palermo in Palermo, Italy, discussed opioid therapy in neuropathic pain. “Responsiveness to opioid drugs varies from patient to patient,” he said.
Opioids develop tolerance and have a ceiling effect that is driven by adverse events. Mercadante emphasised the need to “optimise their use” by staying within the therapeutic window where the benefits outweigh the harm.
Responsiveness depends on genetic polymorphisms affecting receptors and metabolism, pain patterns, age, sex, and psychological distress. “Those with the worst response are patients with significant psychological distress,” he noted.
The opioid escalation index helps to stratify patients. Slow escalation predicts a better prognosis, whereas rapid escalation should prompt specialist involvement and evaluation of factors such as delirium, anxiety, and depression in patients.
Drug Strategies
Switching opioids can be helpful when they become less effective. Mercadante explained that switching opioids “can facilitate receptor internalisation, excluding from continuous stimulation,” allowing “receptor refreshing” and allowing an overstimulated system to be cleared and restoring analgesia. Switching to methadone, when conducted by experienced clinicians, often yields substantial benefits for patients.
Fornasari clarified the mechanisms of action of gabapentinoids, which act on the alpha-2-delta subunit of calcium channels by restoring normal channel numbers rather than by closing them. This distinction is important because it is a slow mechanism that requires approximately 2 weeks for full effect, which is crucial information for clinicians who often discontinue treatment prematurely after a few days of treatment.
Antidepressants, including amitriptyline and serotonin-norepinephrine reuptake inhibitors such as duloxetine, strengthen descending inhibitory pathways by increasing serotonin and noradrenaline levels.
Fornasari also mentioned desvenlafaxine, the active metabolite of venlafaxine, which “has greater activity on descending noradrenergic pathways” and could be particularly useful when the predominant component is noradrenergic.
Topical Options
Capsaicin is an option for chemotherapy-induced peripheral neuropathy.
Chemotherapy-induced neuropathy, the expert explained, is related to the overexpression of transient receptor potential cation channel subfamily V member 1, also known as the capsaicin receptor. Topical capsaicin abnormally stimulates these receptors, causing a massive influx of calcium that “defunctionalises the fibre” for periods ranging from a week to 2 months.
Clinical Takeaways
Therefore, neuropathic pain, particularly in patients with cancer, requires a multimodal approach that begins with an understanding of the molecular mechanisms to develop personalised treatment options. As Fornasari concluded, “Often, a lack of knowledge of a drug’s mechanism of action leads to its inappropriate, and ultimately ineffective, use.” The challenge for clinicians is to translate this knowledge into tangible improvements for patients, remembering that each patient is unique and requires personalised care that goes beyond standardised protocols.
Clinicians aim to translate these insights into meaningful relief, recognising that each patient requires tailored care.
Practical Guidance
- Accurate diagnosis: Screening tools should only be used as support, and decisions should be on the basis of a detailed history and physical examination. In individuals with cancer, the interview always began with the patient’s account.
- Recognising negative prognostic factors: Neuropathic pain, incident pain, psychological distress, delirium, and unrealistic expectations indicate a more difficult course and require a more intensive approach.
- Opioids should be used wisely: Dose escalation should be monitored, rotation should be considered when needed, and psychological factors should be assessed throughout care. As experts have noted, clinicians should try at least 2 or 3 opioids and at least 2 routes of administration before considering invasive procedures.
- Integrating adjuvant medicines early: Gabapentin and other antidepressants are not third-line treatments for individuals with cancer. Adequately dosed for at least 2 weeks to allow therapeutic benefit.
- Consider topical options: In localised peripheral neuropathies, capsaicin can be a valid addition to treatment.
- Use of non-opioid medicines: Some individuals respond exceptionally well to anti-inflammatory agents, with effects that can match those of high morphine doses.
This story was translated from Univadis Italy, part of the this news organization Professional Network.
A version of this article appeared on Medscape.com.
Neuropathic pain in individuals with cancer remains a challenging clinical problem that requires advanced pharmacologic skills and a clear understanding of the molecular mechanisms that drive it.
At the 32nd Annual Congress of the Italian Society of Palliative Care, 3 experts outlined an updated framework that begins with basic biology and leads to the most appropriate therapeutic choice.
Fibre Reprogramming
Diego Maria Michele Fornasari, professor of pharmacology and director of the Postgraduate School of Specialization in Pharmacology and Clinical Toxicology at the University of Milan, Milan, Italy, outlined how a healthy nerve fibre becomes chronically hyperexcitable.
“The pathogenic mechanisms of pain, even though we experience hundreds of different pains, can be counted on the fingers of one hand,” he said.
In oncology, nerve injury caused by tumour compression, chemotherapy, or radiotherapy initiates a molecular cascade that reshapes the nerve fibre.
“The injured area is reprogrammed because the neuron attempts to regenerate, and to regenerate it must express proteins seen during embryonic life,” Fornasari said.
This process leads to the appearance of embryonic sodium channels (particularly Nav1.3), which impart abnormally high electrical activity to neurones.
The second mechanism involves the loss of a protective physiologic feature, namely, intermittent failure of signal conduction. Under normal conditions, occasional conduction failures reduce pain intensity. In neuropathic pain, overexpression of hyperpolarisation–activated cyclic nucleotide-gated channels, the same channels that govern sinoatrial node automaticity, makes the neuron hyperexcitable and unable to modulate transmission. The result is that “all stimuli reach the spinal cord and the central nervous system.”
Fornasari illustrated the concerns regarding pain in bone metastases. “The tumour cell is an intelligent cell, capable of producing substances that can interfere with nociceptive mechanisms,” he said.
He also highlighted the mechanisms of pain in patients with bone metastases. Prostate cancer cells that metastasised to the bone that produce tumour cells produce large amounts of nerve growth factor, which does not promote growth in adult neurones but causes hypertrophy and sprouting of nerve fibres. “Each of these ‘spikes’ is actually a neuropathic lesion of the fibre,” Fornasari explained, clarifying how this mechanism contributes to the often-devastating intensity of pain from bone metastases.
Diagnostic Precision
Francesca Dina Ricchini, oncologist and palliative care specialist working in the Palliative Care Unit at the National Cancer Institute in Milan, Italy, addressed the translation of molecular knowledge into clinical diagnosis. “It is very important to be able to translate these concepts into diagnostic tools,” she said.
Neuropathic involvement affects approximately 40% of individuals with cancer, with 20% presenting with pure neuropathic pain and another 20% with mixed pain.
Approximately 75% of cases are related to the disease itself, and the remainder are related to oncologic treatments. Despite its prevalence, neuropathic pain remains underdiagnosed, contributing to suboptimal analgesia and an impaired quality of life.
Screening tools such as PainDETECT, DN4, and the LANSS scale can support assessment, but Ricchini cautioned that “they are tools that can be used as aids but do not make a diagnosis on their own and have not been validated in oncology patients.”
She noted that quantitative sensory testing (QST) complements clinical judgement by quantifying sensory thresholds for thermal, mechanical, and pain stimuli, aiding in the identification of neuropathic pain mechanisms, particularly in oncology settings. QST can complement clinical judgement and diagnostic algorithms developed by the International Association for the Study of Pain to help clinicians systematically identify neuropathic components.
“The key is to start from symptoms, what the patient tells us,” Ricchini added.
However, bedside assessments remain essential. Simple tool needles, cotton, and the clinician’s thumb allow the evaluation of hyperalgesia, allodynia, and other neuropathic features of the affected area. With careful history taking and physical examination, clinicians can often reach an accurate diagnosis without complex testing.
Opioid Use
Sebastiano Mercadante, director of the Anesthesia & Intensive Care and Pain Relief and Supportive Care Unit in La Maddalena Cancer Center Palermo at the University of Palermo in Palermo, Italy, discussed opioid therapy in neuropathic pain. “Responsiveness to opioid drugs varies from patient to patient,” he said.
Opioids develop tolerance and have a ceiling effect that is driven by adverse events. Mercadante emphasised the need to “optimise their use” by staying within the therapeutic window where the benefits outweigh the harm.
Responsiveness depends on genetic polymorphisms affecting receptors and metabolism, pain patterns, age, sex, and psychological distress. “Those with the worst response are patients with significant psychological distress,” he noted.
The opioid escalation index helps to stratify patients. Slow escalation predicts a better prognosis, whereas rapid escalation should prompt specialist involvement and evaluation of factors such as delirium, anxiety, and depression in patients.
Drug Strategies
Switching opioids can be helpful when they become less effective. Mercadante explained that switching opioids “can facilitate receptor internalisation, excluding from continuous stimulation,” allowing “receptor refreshing” and allowing an overstimulated system to be cleared and restoring analgesia. Switching to methadone, when conducted by experienced clinicians, often yields substantial benefits for patients.
Fornasari clarified the mechanisms of action of gabapentinoids, which act on the alpha-2-delta subunit of calcium channels by restoring normal channel numbers rather than by closing them. This distinction is important because it is a slow mechanism that requires approximately 2 weeks for full effect, which is crucial information for clinicians who often discontinue treatment prematurely after a few days of treatment.
Antidepressants, including amitriptyline and serotonin-norepinephrine reuptake inhibitors such as duloxetine, strengthen descending inhibitory pathways by increasing serotonin and noradrenaline levels.
Fornasari also mentioned desvenlafaxine, the active metabolite of venlafaxine, which “has greater activity on descending noradrenergic pathways” and could be particularly useful when the predominant component is noradrenergic.
Topical Options
Capsaicin is an option for chemotherapy-induced peripheral neuropathy.
Chemotherapy-induced neuropathy, the expert explained, is related to the overexpression of transient receptor potential cation channel subfamily V member 1, also known as the capsaicin receptor. Topical capsaicin abnormally stimulates these receptors, causing a massive influx of calcium that “defunctionalises the fibre” for periods ranging from a week to 2 months.
Clinical Takeaways
Therefore, neuropathic pain, particularly in patients with cancer, requires a multimodal approach that begins with an understanding of the molecular mechanisms to develop personalised treatment options. As Fornasari concluded, “Often, a lack of knowledge of a drug’s mechanism of action leads to its inappropriate, and ultimately ineffective, use.” The challenge for clinicians is to translate this knowledge into tangible improvements for patients, remembering that each patient is unique and requires personalised care that goes beyond standardised protocols.
Clinicians aim to translate these insights into meaningful relief, recognising that each patient requires tailored care.
Practical Guidance
- Accurate diagnosis: Screening tools should only be used as support, and decisions should be on the basis of a detailed history and physical examination. In individuals with cancer, the interview always began with the patient’s account.
- Recognising negative prognostic factors: Neuropathic pain, incident pain, psychological distress, delirium, and unrealistic expectations indicate a more difficult course and require a more intensive approach.
- Opioids should be used wisely: Dose escalation should be monitored, rotation should be considered when needed, and psychological factors should be assessed throughout care. As experts have noted, clinicians should try at least 2 or 3 opioids and at least 2 routes of administration before considering invasive procedures.
- Integrating adjuvant medicines early: Gabapentin and other antidepressants are not third-line treatments for individuals with cancer. Adequately dosed for at least 2 weeks to allow therapeutic benefit.
- Consider topical options: In localised peripheral neuropathies, capsaicin can be a valid addition to treatment.
- Use of non-opioid medicines: Some individuals respond exceptionally well to anti-inflammatory agents, with effects that can match those of high morphine doses.
This story was translated from Univadis Italy, part of the this news organization Professional Network.
A version of this article appeared on Medscape.com.