Pain is frequently reported during cancer disease, and it still remains poorly controlled in 40% of patients. Recent developments in oncology have helped to better control pain. Targeted treatments may cure cancer disease and significantly increase survival. Therefore, a novel population of patients (cancer survivors) has emerged, also enduring chronic pain (27.6% moderate to severe pain). The present review discusses the different options currently available to manage pain in (former) cancer patients in light of progress made in the last decade. Major progress in the field includes the recent development of a chronic cancer pain taxonomy now included in the International Classification of Diseases (ICD-11) and the update of the WHO analgesic ladder. Until recently, cancer pain management has mostly relied on pharmacotherapy, with opioids being considered as the mainstay. The opioids crisis has prompted the reassessment of opioids use in cancer patients and survivors. This review focuses on the current utilization of opioids, the neuropathic pain component often neglected, and the techniques and non-pharmacological strategies available which help to personalize patient treatment. Cancer pain management is now closer to the management of chronic non-cancer pain, i.e., “an integrative and supportive pain care” aiming to improve patient’s quality of life.

Cancer Pain Management: A Narrative Review of Current Concepts, Strategies, and Techniques

Is depression the missing link between inflammatory mediators and cancer?

Ketamine is a well-characterized anesthetic agent, and subanesthetic ketamine possesses analgesic effects in both acute and chronic pain.A systematic review was performed to ascertain the efficacy and safety of ketamine in treating pain for cancer patients.Eight databases were searched from the inception to March 20th, 2023 to obtain randomized controlled trials (RCTs) on ketamine for treating pain in cancer patients. Two reviewers independently screened studies, extracted the data and assessed the risk of bias of included studies; then, meta-analysis was performed by using Revman 5.3 software and Stata 14.0 software.Thirty-five studies were included, involving 2279 patients with cancer pain. The results of meta-analysis showed that ketamine could significantly reduce pain intensity. Subgroup analysis revealed that, when compared with control group, ketamine decreased markedly visual analogue scale (VAS) scores in two days after the end of treatment with ketamine, and ketamine administrated by patient controlled epidural analgesia (PCEA) was effective. Meanwhile, ketamine could significantly reduce the number of patient-controlled analgesia (PCA) compressions within 24 hours and morphine dosage. Ketamine could not decrease Ramsay sedation score. Additionally, the adverse events significantly decreased in the ketamine group, including nausea and vomiting, constipation, pruritus, lethargy, uroschesis, hallucination, and respiratory depression. In addition, compared with the control group, ketamine could reduce Hamilton depression scale (HAMD) score and relieve depressive symptoms.Ketamine may be used as an effective therapy to relieve cancer pain. However, more rigorously designed RCTs with larger sample sizes are required to verify the above conclusions. 

Efficacy and safety of ketamine to treat cancer pain in adult patients: A systematic review.

Acetylcholine is the primary excitatory neurotransmitter in visceral smooth muscles, wherein it binds to and activates two muscarinic receptors subtypes, M2 and M3, thus causing smooth muscle excitation and contraction. The first part of this review focuses on the types of cells involved in cholinergic neurotransmission and on the molecular mechanisms underlying acetylcholine-induced membrane depolarisation, which is the central event of excitation-contraction coupling causing Ca2+ entry via L-type Ca2+ channels and smooth muscle contraction. Studies of the muscarinic cation current in intestinal myocytes (mICAT) revealed its main molecular counterpart, receptor-operated TRPC4 channel, which is activated in synergy by both M2 and M3 receptors. M3 receptors activation is of permissive nature, while activation of M2 receptors via Gi/o proteins that are coupled to them plays a direct role in TRPC4 opening. Our understanding of signalling pathways underlying mICAT generation has vastly expanded in recent years through studies of TRPC4 gating in native cells and its regulation in heterologous cells. Recent studies using muscarinic receptor knockout have established that at low agonist concentration activation of both M2 receptor and the M2/M3 receptor complex elicits smooth muscle contraction, while at high agonist concentration M3 receptor function becomes dominant. Based on this knowledge, in the second part of this review we discuss the cellular and molecular mechanisms underlying the numerous anticholinergic effects on neuroactive drugs, in particular general anaesthetics and anxiolytics, which can significantly impair gastrointestinal motility. This article is part of the Special Issue on “Ukrainian Neuroscience”. 

Molecular mechanisms of cholinergic neurotransmission in visceral smooth muscles with a focus on receptor-operated TRPC4 channel and impairment of gastrointestinal motility by general anaesthetics and anxiolytics

The Impact of Chronic Diseases on Mental Health: An Overview and Recommendations for Care Programs.

Preventing depression in cancer patients on long-term opioid therapy should begin with depression screening before opioid initiation and repeated screening during treatment. In weighing the high morbidity of depression and opioid use disorder in patients with chronic cancer pain against a dearth of evidence-based therapies studied in this population, patients and clinicians are left to choose among imperfect but necessary treatment options. When possible, we advise engaging psychiatric and pain/palliative specialists through collaborative care models and recommending mindfulness and psychotherapy to all patients with significant depression alongside cancer pain. Medications for depression should be reserved for moderate to severe symptoms. We recommend escitalopram/citalopram or sertraline among selective serotonin reuptake inhibitors (SSRIs), or the serotonin and norepinephrine reuptake inhibitors (SNRIs) duloxetine, venlafaxine, or desvenlafaxine if patients have a significant component of neuropathic pain or fibromyalgia. Tricyclic antidepressants (TCAs) (consider nortriptyline or desipramine, which have better anticholinergic profiles) should be considered for patients who do not respond to or tolerate SSRI/SNRIs. Existing evidence is inadequate to definitively recommend methylphenidate or novel agents, such as ketamine or psilocybin, as adjunctive treatments for cancer-related depression and pain. Physicians who treat patients with cancer pain should utilize universal precautions to limit the risk of non-medical opioid use (non-medical opioid use). Patients should be screened for non-medical opioid use behaviors at initial consultation and at regular intervals during treatment using a non-judgmental approach that reduces stigma. Co-management with an addiction specialist may be indicated for patients at high risk of non-medical opioid use and opioid use disorder. Buprenorphine and methadone are indicated for the treatment of opioid use disorder, and while they have not been systematically studied for treatment of opioid use disorder in patients with cancer pain, they do provide analgesia for cancer pain. While an interdisciplinary team approach to manage psychological stress may be beneficial, this may not be possible for patients treated outside of comprehensive cancer centers. 

/pdf/depression-and-long-term-prescription-opioid-use-and-opioid-2z6wh1o3.pdf

Depression and Long-Term Prescription Opioid Use and Opioid Use Disorder: Implications for Pain Management in Cancer

SCOPE: Examining Technology-Enhanced Collaborative Care Management of Depression in the Cancer Setting

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Depression and Long-Term Prescription Opioid Use and Opioid Use Disorder: Implications for Pain Management in Cancer

SCOPE: Examining Technology-Enhanced Collaborative Care Management of Depression in the Cancer Setting