Pathophysiology of pain in cancer and other terminal illnesses

Cancer pain involves a myriad of peripheral changes in the function of tissues and nerves, at the site of the tumour growth, as well as a number of consequent changes in the processing of pain messages at the spinal cord level with implications for the pain experience at higher centres. This chapter reviews the changes in peripheral pain signalling, notes the likely prevalence of both inflammatory and neuropathic components, and describes the altered events at spinal levels and within the circuits of pain in higher brain areas that can help explain the ongoing pain, hyperalgesia, and allodynia that patients with cancer and other chronic illnesses, such as HIV/AIDs, experience. The mechanisms of action of therapies, both existing and potential novel approaches, are also described. The importance of these processes in the development and treatment of chronic pain is an emerging issue, particularly as the problem of persistent pain in cancer survivors increases in prevalence.

Prolonged Pain Reliably Slows Peak Alpha Frequency by Reducing Fast Alpha Power

The relationship between the 8-12 Hz alpha rhythm, the predominant oscillatory activity of the brain, and pain remains unclear. In healthy individuals, acute, noxious stimuli suppress alpha power while patients with chronic pain demonstrate both enhanced alpha power and slowing of the peak alpha frequency (PAF). To investigate these apparent differences, EEG was recorded from healthy individuals while they completed two models of prolonged pain, Phasic Heat Pain and Capsaicin Heat Pain, at two testing visits occurring roughly 8 weeks apart. We report that PAF is reliably slowed and that alpha power is reliably decreased in response to prolonged pain. Furthermore, we show that alpha power changes, but not PAF changes, are fully reversed with stimulus removal suggesting that PAF slowing reflects pain associated states such as sensitization rather than the presence of ongoing pain. Finally, we provide evidence that changes to alpha power and PAF are due to power decreases in the fast (10-12 Hz) range of the alpha rhythm. This frequency dependent pain response aligns with the hypothesis that the alpha rhythm is composed of multiple, independent oscillators, and suggest that modulation of a putative fast oscillator may represent a promising therapeutic target for treating ongoing pain. In sum, we provide strong evidence that PAF is reliably slowed during prolonged pain and additionally identify a mechanism, fast alpha Power, which is responsible for these PAF changes.

Prevalence of Chemotherapy-Induced Peripheral Neuropathy in Multiple Myeloma Patients and its Impact on Quality of Life: A Single Center Cross-Sectional Study

Bortezomib is a pivotal drug for the management of multiple myeloma. However, bortezomib is a neurotoxic anticancer drug responsible for chemotherapy-induced peripheral neuropathy (CIPN). CIPN is associated with psychological distress and a decrease of health-related quality of life (HRQoL), but little is known regarding bortezomib-related CIPN. This single center, cross-sectional study assessed the prevalence and severity of sensory/motor CIPN, neuropathic pain and ongoing pain medications, anxiety, depression, and HRQoL, in multiple myeloma patients after the end of bortezomib treatment. Paper questionnaires were sent to patients to record the scores of sensory and motor CIPNs (QLQ-CIPN20), neuropathic pain (visual analogue scale and DN4 interview), anxiety and depression (HADS), the scores of HRQoL (QLQ-C30 and QLQ-MY20) and ongoing pain medications. Oncological data were recorded using chemotherapy prescription software and patient medical records. The prevalence of sensory CIPN was 26.9% (95% CI 16.7; 39.1) among the 67 patients analyzed and for a mean time of 2.9 ± 2.8 years since the last bortezomib administration. The proportion of sensory CIPN was higher among patients treated by intravenous and subcutaneous routes than intravenous or subcutaneous routes (p = 0.003). QLQ-CIPN20 motor scores were higher for patients with a sensory CIPN than those without (p < 0.001) and were correlated with the duration of treatment and the cumulative dose of bortezomib (coefficient: 0.31 and 0.24, p = 0.01 and 0.0475, respectively), but not sensory scores. Neuropathic pain was screened in 44.4% of patients with sensory CIPN and 66.7% of them had ongoing pain medications, but none were treated with duloxetine (recommended drug). Multivariable analysis revealed that thalidomide treatment (odds-ratio: 6.7, 95% CI 1.3; 35.5, p = 0.03) and both routes of bortezomib administration (odds-ratio: 13.4, 95% CI 1.3; 139.1, p = 0.03) were associated with sensory CIPN. Sensory and motor CIPNs were associated with anxiety, depression, and deterioration of HRQoL. Sensory CIPN was identified in a quarter of patients after bortezomib treatment and associated with psychological distress that was far from being treated optimally. There is a need to improve the management of patients with CIPN, which may include better training of oncologists regarding its diagnosis and pharmacological treatment.

Virtual Reality Based Passive and Active Distraction Methods for the Treatment of Chronic Pain

<p>Chronic pain is ongoing pain lasting for long periods after the initial injury or disease has healed. Chronic pain is difficult to treat and can affect the daily lives of patients. Distraction therapy is a proven way of relieving pain for patients by taking their attention away from the pain. Virtual reality is a platform for distraction therapy by immersing the user visually, aurally, and even somewhat physically in a virtual world detached from reality. There is little research done regarding the effects virtual reality's physical interactions have on pain management. This project aims to evaluate different types of virtual reality interactions for chronic pain patients to determine which is most effective for pain relief. The results found that physical and mental activities in virtual reality are equally effective as each other at reducing pain while the patients are engaged in the content, while the effects of observing relaxing content persists outside of virtual reality. These results inform the design of future virtual reality games targeted at pain management.</p>

Virtual Reality Based Passive and Active Distraction Methods for the Treatment of Chronic Pain

<p>Chronic pain is ongoing pain lasting for long periods after the initial injury or disease has healed. Chronic pain is difficult to treat and can affect the daily lives of patients. Distraction therapy is a proven way of relieving pain for patients by taking their attention away from the pain. Virtual reality is a platform for distraction therapy by immersing the user visually, aurally, and even somewhat physically in a virtual world detached from reality. There is little research done regarding the effects virtual reality's physical interactions have on pain management. This project aims to evaluate different types of virtual reality interactions for chronic pain patients to determine which is most effective for pain relief. The results found that physical and mental activities in virtual reality are equally effective as each other at reducing pain while the patients are engaged in the content, while the effects of observing relaxing content persists outside of virtual reality. These results inform the design of future virtual reality games targeted at pain management.</p>

A spinoparabrachial circuit defined by Tacr1 expression drives pain

Painful stimuli evoke a mixture of sensations, negative emotions and behaviors. These myriad effects are thought to be produced by parallel ascending circuits working in combination. Here we describe a pathway from spinal cord to brain for ongoing pain. Activation of a subset of spinal neurons expressing Tacr1 evokes a full repertoire of somatotopically-directed pain-related behaviors in the absence of noxious input. Tacr1 projection neurons (expressing NKR1) target a tiny cluster of neurons in the superior lateral parabrachial nucleus (PBN-SL). We showed that these neurons, which also express Tacr1 (PBN-SLTacr1), are responsive to sustained but not acute noxious stimuli. Activation of PBN-SLTacr1 neurons alone did not trigger pain responses but instead served to dramatically heighten nocifensive behaviors and suppress itch. Remarkably, mice with silenced PBN-SLTacr1 neurons ignored long-lasting noxious stimuli. Together, these data reveal new details about this spinoparabrachial pathway and its key role in the sensation of ongoing pain.

Efficacy of cholecystectomy in patients with positive HIDA Scans with typical or atypical biliary pain: A retrospective study

Introduction: Our investigation aimed to discover the benefits of performing cholecystectomy in patients who had a positive or negative HIDA scan result, presented with either typical or atypical biliary pain. Methods: We performed a retrospective analysis of medical records of patients who had a HIDA scan at Peninsula Health between 2012 and 2017, those who had a HIDA scan and cholecystectomy for biliary pain were selected for this study, and prospective analysis of patient reported outcome post cholecystectomy included. Results: In the past five years, 190 patients had had a HIDA scan to investigate biliary pain without a structural cause. Of those 190, 65 had a positive HIDA result and 20 of these patients went on to have a cholecystectomy. Of the latter, 17 who reported typical biliary pain had their pain resolved post-surgery but 2 out of 3 patients with atypical biliary pain had ongoing pain despite surgery (1 did not respond). Of the 125 patients with a negative HIDA scan, 14 proceeded with a cholecystectomy. Twelve patients had pre-operative typical biliary pain and 5 of these continued to have pain post-operatively. Finally, 1 of the 2 patients with atypical pain continued to have ongoing pain post-surgery. Conclusion: In summary, in patients without a structural cause for biliary pain HIDA scans and patient’s symptoms greatly aid in the decision-making process whether to proceed with a cholecystectomy, as a negative scan should prompt further clinical investigation before proceeding with surgery.

Pain Management in Childhood Leukemia: Diagnosis and Available Analgesic Treatments

Pain is one of the most common symptoms in children suffering from leukemia, who are often misdiagnosed with other childhood painful diseases such as juvenile idiopathic arthritis. Corticosteroid-induced osteonecrosis (ON) and vincristine-induced peripheral neuropathy (VIPN) are the most common painful manifestations. Additionally, ongoing pain may continue to impact quality of life in survivorship. This narrative review focuses on the pathophysiological mechanisms of pain in childhood leukemia and current available indications for analgesic treatments. Pain management in children is often inadequate because of difficulties in pain assessment, different indications across countries, and the lack of specific pediatric trials. Analgesic drugs are often prescribed off-label to children by extrapolating information from adult guidelines, with possible increased risk of adverse events. Optimal pain management should involve a multidisciplinary team to ensure assessment and interventions tailored to the individual patient.