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Mechanisms of chemotherapy-induced behavioral toxicities.

While chemotherapeutic agents have yielded relative success in the treatment of cancer, patients are often plagued with unwanted and even debilitating side-effects from the treatment which can lead to dose reduction or even cessation of treatment. Common side effects (symptoms) of chemotherapy include (i) cognitive deficiencies such as problems with attention, memory and executive functioning; (ii) fatigue and motivational deficit; and (iii) neuropathy. These symptoms often develop during treatment but can remain even after cessation of chemotherapy, severely impacting long-term quality of lif

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… The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain . J. Neuroinflammation 9 , 180 . 10.1186/1742-2094-9-180 22824385 PMC3488576 Flanary B. E. Streit W. J. ( 2004 ). … Spinal CCL2 and microglial activation are involved in paclitaxel-evoked cold hyperalgesia . Brain Res. Bull . 95 , 21 – 27 . 10.1016/j.brainresbull.2013.03.005 23562605 Podratz J. L. Knight A. M. Ta L. E. Staff N. P. Gass J. M. Genelin K. . ( 2011 ). …

Acupuncture for post-chemoradiotherapy complications in lung cancer with bone metastasis: a case report and literature review.

Despite significant advances in oncologic therapeutics, chemoradiotherapy-induced complications, including chemotherapy-induced peripheral neuropathy (CIPN) and hip dysfunction, remain clinically challenging to manage with pharmacological interventions alone. This report presents the case of a 52-year-old male with a history of right-sided lung cancer resection performed more than three years previously and confirmed bone metastasis for over two years. Following metastasis to the right ilium and acetabulum, the patient developed pain, numbness, gait disturbance, and impaired mobility in the ri

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… Paclitaxel can induce mainly sensory axonal neuropathy and painful distal sensory neuropathy, including mechanical hyperalgesia, cold hyperalgesia, continuous burning pain, tingling, and numbness ( 38 ). … Acupuncture stimulates nociceptive Aδ and C fibers, modulates neuronal activity in the spinal dorsal horn after chemotherapy, and improves symptoms of peripheral neuropathy, including pain, burning sensation, numbness, hyperesthesia, hyperalgesia, impaired temperature discrimination, and gait disturbances …

Cancer Pain Is Not One-Size-Fits-All: Evolving from Tradition to Precision.

Cancer pain remains a significant challenge in oncology, profoundly affecting patients' quality of life, function, and prognosis. Historically under-recognized and managed with a uniform, opioid-centric approach, cancer pain was often inadequately treated. Advances in pain assessment, multimodal analgesia, and supportive care have improved outcomes, yet traditional algorithms frequently fail to address the complex, heterogeneous nature of cancer pain. Contemporary management is shifting toward precision and personalized medicine, integrating genetic, molecular, and biomarker data with individu

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… Opioid-Induced Hyperalgesia Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon wherein patients utilizing opioids for analgesia exhibit heightened pain sensitivity, indicating that these drugs may exacerbate pain rather than alleviate it. … N-methyl-D-aspartate SREs | skeletal-related events PEA | Palmitoylethanolamide MORs | mu opioid receptors IV | intravenous SC | subcutaneous ASCO | American Society of Clinical Oncology IR | Immediate-Release ER | Extended-Release PRN | Pro re nata “as needed” MME | morphine oral equivalent OIH | Opioid-induced hyperalgesia …

Differential Pain-Related Behaviors and Bone Disease in Immunocompetent Mouse Models of Myeloma.

Bone pain is a serious and debilitating symptom of multiple myeloma (MM) that impairs the quality of life of patients. The underlying mechanisms of the pain are unknown and understudied, and there is a need for immunocompetent preclinical models of myeloma-induced bone pain. The aim of this study was to provide the first in-depth behavioral characterization of an immunocompetent mouse model of MM presenting the clinical disease features: osteolytic bone disease and bone pain. We hypothesized that a widely used syngeneic model of MM, established by systemic inoculation of green fluorescent prot

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… Hot plate test Thermal hyperalgesia was evaluated on a Hot Plate Analgesia Meter (Harvard Apparatus, Holliston, MA, USA) set at 52.5 ± 0.1°C, by quantifying the time lapse between animal exposure to the apparatus and a positive response. … Similar to the systemic model, mechanical allodynia and thermal hyperalgesia were unchanged in myeloma‐bearing mice (Fig. 4 A , B ). …

Chemotherapy-induced peripheral neuropathy in children and adolescent cancer patients.

Brain cancer and leukemia are the most common cancers diagnosed in the pediatric population and are often treated with lifesaving chemotherapy. However, chemotherapy causes severe adverse effects and chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting and debilitating side effect. CIPN can greatly impair quality of life and increases morbidity of pediatric patients with cancer, with the accompanying symptoms frequently remaining underdiagnosed. Little is known about the incidence of CIPN, its impact on the pediatric population, and the underlying pathophysiological mecha

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… Sensory symptoms include paresthesia, dysesthesia, hyperalgesia, allodynia, numbness, pain and loss of proprioception. … However, cisplatin causes paresthesia, tingling in the extremities, numbness, mechanical and thermal hyperalgesia, loss of vibration sense and taste, weakness, tremor, constipation, and diarrhea ( Kandula et al., 2016 ). …

Effects of short-term combined treatment with alendronate and elcatonin on bone mineral density and bone turnover in postmenopausal women with osteoporosis.

The antiresorptive drug elcatonin (ECT) is known to relieve pain in postmenopausal women with osteoporosis. A prospective open-labeled trial was conducted to compare the effects of short-term combined treatment with alendronate (ALN) and ECT on bone mineral density (BMD) and bone turnover with those of single treatment with ALN in postmenopausal women with osteoporosis. Two hundred and five postmenopausal osteoporotic women (mean age: 70 years) were recruited in our outpatient clinic. Forty-six women with back pain were treated with ALN and ECT (intramuscular, 20 units a week), and 159 women w

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… There are no significant differences in the analgesic effect of eel and salmon calcitonins and their influence on the morphine-analgesia. 29 Estrogen deficiency not only causes bone loss, but also affects the spinal serotonergic system (serotonergic receptor expression), resulting in hyperalgesia. … Ovariectomy-induced hyperalgesia and antinociceptive effect of elcatonin, a synthetic eel calcitonin. Pharmacol Biochem Behav. 1998;60:371–376. doi: 10.1016/s0091-3057(98)00015-x. 29. Martin MI, Goicoechea C, Ormazabal MJ, et al. …

[Effects and mechanisms of Yuxuebi Tablets combined with ibuprofen in treating chronic musculoskeletal pain through "integrated regulation of inflammation and pain-related oxylipins"].

This study adopted a three-dimensional "effect-dose-mechanism" evaluation system to screen the optimal regimen of Yuxuebi Tablets( … D1 to D18. During this period, mechanical pain threshold was measured by the Von Frey test; thermal hyperalgesia was detected by the hot plate test, and depression-like behavior was observed by the tail suspension test. After treatment, peripheral blood was collected from all groups for complete blood biochemical analysis, and the injected feet of the sham, CF …

Effect of Epidural Block in the Incidence of Postherpetic Neuralgia: A Population-Based Matched-Cohort Study.

BACKGROUND: Incidence of postherpetic neuralgia (PHN) increases with age. Epidural block in patients with herpes zoster (HZ) is expected to decrease the risk of PHN. The purpose of this study was to evaluate the effectiveness of epidural block on PHN incidence in a population-based study. METHODS: This was a retrospective matched cohort study and data were sourced from the Korean National Health Insurance Service. The study cohort comprised 427 patients diagnosed with HZ who received epidural block within 30 days after a diagnosis of HZ. The matched control cohort included 427 patients withou

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… In each study, based on pain scales (numerical rating scale or visual analog scale), PHN was defined differently: higher than 10/100, 2 , 13 , 16 - 18 , 27 ) 25/100, 28 ) and 30/100. 2 ) Furthermore, PHN has a wide spectrum of symptoms including spontaneous pain, paroxysmal pain, allodynia, hyperalgesia … The pathophysiology of PHN remains unclear. 21 ) In patients with PHN, damage to the sensory nerve, dorsal root ganglion, and dorsal horn of the spinal cord has been reported. 29 ) These injuries can result in pain, allodynia, and hyperalgesia. …

TrkA abundance is increased in cutaneous nerves in bortezomib-induced neuropathy.

Tropomyosin receptor kinase A (TrkA), a high-affinity receptor for nerve growth factor (NGF), is implicated in nociception and local angiogenesis. We investigated TrkA localization and abundance in skin biopsies from multiple myeloma patients who developed peripheral neuropathy during bortezomib treatment. We recruited 50 multiple myeloma patients with bortezomib-induced peripheral neuropathy (BIPN), including 31 without pain and 19 with pain, and 27 matched healthy controls at University Hospital Würzburg (2021-2024). Skin biopsies from the distal leg were analyzed to determine intraepidermal

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… Biochem Biophys Res Commun . 2014 ; 444 ( 3 ): 415 – 419 . 24480438 10.1016/j.bbrc.2014.01.082 9 Ji RR , Samad TA , Jin SX , Schmoll R , Woolf CJ . p38 MAPK activation by NGF in primary sensory neurons after inflammation increases TRPV1 levels and maintains heat hyperalgesia . … The TrkA receptor mediates experimental thermal hyperalgesia produced by nerve growth factor: modulation by the p75 neurotrophin receptor . …

Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.

Many common cancers such as breast, prostate, and lung cancer metastasize to bones at advanced stages, producing severe pain and functional impairment. At present, the current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. In this narrative review, we discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain. In particular, we highlight the reciprocal interactions between tumor cells, bone-resorbing osteoclasts, and pain-sensing sensory neurons (nociceptors), which drive bon

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… Superficial dorsal horn neuronal responses and the emergence of behavioural hyperalgesia in a rat model of cancer-induced bone pain. Neurosci Lett 2004;360:29–32. [28] Donovan-Rodriguez T, Dickenson AH, Urch CE. … Tumor-evoked hyperalgesia and sensitization of nociceptive dorsal horn neurons in a murine model of cancer pain. Brain Res 2007;1180:7–19. [47] Khodorova A, Navarro B, Jouaville LS, Murphy JE, Rice FL, Mazurkiewicz JE, Long-Woodward D, Stoffel M, Strichartz GR, Yukhananov R, Davar G. …

Периоперативные соображения для пациентов с множественной миеломой.

Множественная миелома — неизлечимый рак, характеризующийся распространением клональных плазменных клеток, в основном в костном мозге, но вызывающий широкомасштабные системные осложнения. Кроме того, этот рак обычно встречается у пожилых пациентов, которые часто являются слабыми и страдают от многочисленных коморбидов. Общемировая распространенность множественной миеломы неуклонно возрастает, а терапевтические достижения способствуют повышению уровня выживания. Существует несколько осложнений миеломы, о которых анестезиолог должен знать в связи с самим заболеванием, конкретными и подкрепляющими

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… remains a particular challenge, compounded by factors such as preexisting bone pain, NSAIDs contraindications, renal dysfunction affecting drug metabolism, and limitations to neuraxial techniques. 102 Prolonged opioid exposure from chronic pain may result in opioid tolerance or opioid-induced hyperalgesia … recommended, with adjuvant agents including ketamine, lignocaine infusion, dexmedetomidine, paracetamol, and magnesium, alongside regional nerve blocks where appropriate, offering valuable opioid-sparing options. 44 , 102 , 103 Low-dose ketamine has demonstrated particular benefit in opioid tolerance and hyperalgesia …

Tapentadol prolonged release for patients with multiple myeloma suffering from moderate-to-severe cancer pain due to bone disease.

CONTEXT: Myeloma bone disease (MBD) is a devastating complication of multiple myeloma that leads to severe pain. OBJECTIVES: The aim of this study was to evaluate the efficacy and tolerability of tapentadol prolonged release (PR) in the management of patients with MBD suffering from moderate-to-severe cancer pain. METHODS: A 12-week prospective study was carried out in 25 opioid-naïve MBD patients. Patients initially received twice-daily doses of tapentadol PR 50 mg. Doses were then managed to maintain adequate relief or dose-limiting toxicity. The following parameters were recorded at weekl

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… Negative signs, such as the loss of light touch, vibration, pinprick, or thermal sensation, may be accompanied by positive signs, such as allodynia, hyperalgesia, and hyperpathia. … Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain Eur J Pain 2010 14 814 821 20541444 10.1016/j.ejpain.2010.05.005 9 Christoph T De Vry J Tzschentke TM Tapentadol, but not morphine, selectively inhibits disease-related thermal hyperalgesia …

Spinal glia and proinflammatory cytokines mediate mirror-image neuropathic pain in rats.

Mirror-image allodynia is a mysterious phenomenon that occurs in association with many clinical pain syndromes. Allodynia refers to pain in response to light touch/pressure stimuli, which normally are perceived as innocuous. Mirror-image allodynia arises from the healthy body region contralateral to the actual site of trauma/inflammation. Virtually nothing is known about the mechanisms underlying such pain. A recently developed animal model of inflammatory neuropathy reliably produces mirror-image allodynia, thus allowing this pain phenomenon to be analyzed. In this sciatic inflammatory neurop

The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.

The bidirectional crosstalk between the nervous system and tumors has emerged as a transformative new frontier in both precision oncotherapy and mechanism-driven cancer pain management. Marine natural products with inherent neuroactive properties exhibit unparalleled intervention advantages for targeting this complex pathophysiological axis. Herein, we systematically and prospectively dissect the multi-layered bidirectional communication between the nervous system and malignancies, comprehensively summarize the pivotal contributions of marine-derived bioactive molecules to advances in neurosci

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… In aggressive models, such as breast cancer bone metastasis and oral squamous cell carcinoma, TRPV1 is further sensitized via crosstalk with protease-activated receptor 2 (PAR2), markedly enhancing metastatic colonization and hyperalgesia [ 32 , 33 ]. … Specifically, the overexpression of Na V 1.7 leads to increased excitability and ectopic discharges, culminating in hyperalgesia [ 135 ]. …

Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies.

BackgroundPeripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy.MethodThe current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of

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… All these mechanisms culminate in damage to the sensory neurons such as Aδ and C fibers, leading to neuropathic pain characterized by hyperalgesia and allodynia. However, oxidative stress and mitochondrial dysfunction have been suggested to be major contributors in the pathophysiology of CIPN. … Spinal glial glutamate transporters downregulate in rats with taxol-induced hyperalgesia. Neurosci. Lett. 2005;386(1):18–22. doi: 10.1016/j.neulet.2005.05.049. [http://dx.doi.org/10.1016/j.neulet.2005.05.049]. [PMID: 15975716]. 55. Flatters S.J., Bennett G.J. …

Melittin, a honeybee venom derived peptide for the treatment of chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most prevalent neurological complication of cancer treatment which involves sensory and motor nerve dysfunction. Severe CIPN has been reported in around 5% of patients treated with single and up to 38% of patients treated with multiple chemotherapeutic agents. Present medications available for CIPN are the use of opioids, nonsteroidal anti-inflammatory agents, and tricyclic antidepressants, which are only marginally effective in treating neuropathic symptoms. In reality, symptom reappears after these drugs are discontinued. The pathogene

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… Particularly, in case of chemotherapy-induced neuropathy, melittin ameliorated the condition by improving mechanical hyperalgesia, cold allodynia and spinal wide dynamic range. Despite that, their usage has often been limited due to its side effects, mainly haemolysis. … Roh DH Kwon YB Kim HW Ham TW Yoon SY Kang SY Han HJ Lee HJ Beitz AJ Lee JH Acupoint stimulation with diluted bee venom (apipuncture) alleviates thermal hyperalgesia in a rodent neuropathic pain model: involvement of spinal alpha2-adrenoceptors J Pain 2004 5 6 297 303 15336634 10.1016/j.jpain.2004.05.003 …

Chemotherapy-Induced Peripheral Neuropathy: Epidemiology, Pathomechanisms and Treatment.

PurposeThis review provides an update on the current clinical, epidemiological and pathophysiological evidence alongside the diagnostic, prevention and treatment approach to chemotherapy-induced peripheral neuropathy (CIPN).FindingsThe incidence of cancer and long-term survival after treatment is increasing. CIPN affects sensory, motor and autonomic nerves and is one of the most common adverse events caused by chemotherapeutic agents, which in severe cases leads to dose reduction or treatment cessation, with increased mortality. The primary classes of chemotherapeutic agents associated with CI

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… Reduction of oxidative stress with phenyl N -tert-butylnitrone has been shown to decrease oxaliplatin-induced mechanical hyperalgesia and cold allodynia [ 62 , 63 ]. … Both ROS and neuroinflammation are implicated in nociceptor sensitisation, mechanical hyperalgesia and cold allodynia in preclinical models. …

Neuropathic-like symptoms and central sensitization related signs and symptoms negatively affect the functional performance of patients with knee osteoarthritis - a cross-sectional study.

OBJECTIVE: This study aimed to compare the functional performance among participants with a neuropathic-like symptoms (NS) and central sensitization related signs and symptoms (CS), and their knee osteoarthritis (OA) counterparts. METHODS: A cross-sectional observational study was conducted with 125 participants with knee OA (94 females, mean age 63.1 ​± ​7.4 years). Participants completed a self-reported questionnaire with personal and clinical features and musculoskeletal pain characteristics, including NS (PainDETECT), CS (Central Sensitization Inventory, CSI), and conditioned pain modulat

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… Furthermore, patients with neuropathic pain have a more significant functional impairment, multimodal hyperalgesia, and greater pain sensitivity [ 14 ]. Therefore, measuring the impact of NS on the functionality of patients with knee OA can assist therapeutic management of this population. … Patients with knee osteoarthritis who score highly on the PainDETECT questionnaire present with multimodality hyperalgesia, increased pain, and impaired physical function. Clin. J. Pain. 2018;34:15–21. doi: 10.1097/AJP.0000000000000504. 15. Fingleton C., Smart K., Moloney N., Fullen B.M., Doody C. …

The role of complementary and alternative methods in the treatment of pain in patients with cancer - current evidence and clinical practice: a narrative review.

IntroductionPain related to cancer, despite the numerous treatment options available, is still a challenge in contemporary pain medicine. The unsatisfactory treatment of cancer pain is one of the main reasons why patients seek complementary and alternative methods (CAM) and a more integrative/holistic approach to pain management. The popularity of CAM forces healthcare professionals to provide patients with current and evidence-based information on the effectiveness and safety of CAM. The aim of the paper is to present current evidence and limitations regarding CAM commonly used in the pain ma

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… The analgesic mechanism of exercises is not yet fully understood, but the beneficial effect of exercises may be associated with centrally mediated enhanced conditioned pain modulation, normalization of the neuroimmune signalling in the CNS, and subsequent reduction of hyperalgesia, as well as body mass … Effectiveness of transcutaneous electrical nerve stimulation for treatment of hyperalgesia and pain. Curr Rheumatol Rep 2008; 6: 492-499. 43. Ma YT, Sluka KA. Reduction in inflammation induced sensitization of dorsal horn neurons by transcutaneous electrical nerve stimulation in anesthetized rats. …

Cancer treatment-related neuropathic pain: proof of concept study with menthol--a TRPM8 agonist.

PurposeEffective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol.Patients and methodsPatients with problematic treatment-related neuropathic pa

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… Symptoms are commonly in a glove and stocking distribution and include spontaneous pain, paraesthesia, allodynia (nonpainful stimuli causing pain), hyperalgesia (increased sensitivity to painful stimuli), hypoaesthesia (numbness) and impaired proprioception, causing difficulty with day-to-day functioning … Mechanical pain sensitivity (hyperalgesia) was tested using noxious pin prick stimulus (Neurotips TM Owen Mumford) and rated using an NRS from 0 to 10. v. Temporal summation was assessed using five rapidly repeated pin prick stimuli and a NRS rating. …