Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain

Brandolini, Laura; d’Angelo, Michele; Antonosante, Andrea; Allegretti, Marcello; Cimini, Annamaria

doi:10.3390/ijms20122904

Cited by 77 publications

(67 citation statements)

References 115 publications

(162 reference statements)

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“…Methotrexate activated microglia, but no changes in CNS cytokine levels were observed (Seigers et al , ). In contrast, several chemotherapeutic drugs, including methotrexate, cisplatin, oxaliplatin, paclitaxel, and vincristine, elevated peripheral inflammatory cytokines to induce chronic pain (Brandolini et al , ). Elevation of peripheral cytokines may also penetrate the blood–brain barrier to directly act on the CNS, and to activate microglia and astrocytes to secrete further cytokines.…”

Section: Introductionmentioning

confidence: 99%

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

2020

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Chemotherapy is a life-saving treatment for cancer patients, but also causes long-term cognitive impairment, or "chemobrain", in survivors. However, several challenges, including imprecise diagnosis criteria, multiple confounding factors, and unclear and heterogeneous molecular mechanisms, impede effective investigation of preventions and treatments for chemobrain. With the rapid increase in the number of cancer survivors, chemobrain is an urgent but unmet clinical need. Here, we leverage the extensive knowledge in various fields of neuroscience to gain insights into the mechanisms for chemobrain. We start by outlining why the post-mitotic adult brain is particularly vulnerable to chemotherapy. Next, through drawing comparisons with normal aging, Alzheimer's disease, and traumatic brain injury, we identify universal cellular mechanisms that may underlie the cognitive deficits in chemobrain. We further identify existing neurological drugs targeting these cellular mechanisms that can be repurposed as treatments for chemobrain, some of which were already shown to be effective in animal models. Finally, we briefly describe future steps to further advance our understanding of chemobrain and facilitate the development of effective preventions and treatments.Cognitive complaints are common among cancer patients during and after chemotherapy. Cross-sectional and longitudinal studies suggest that short-term memory, working memory, and verbal ability are most frequently affected, followed by visuospatial memory, executive functions, and attention span (for meta-analyses, see

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Section: Introductionmentioning

confidence: 99%

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

2020

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“…interleukin‐1 β (IL‐1 β ), IL‐18, IL‐6 and nitric oxide synthase 2 (NOS2)] and antinociceptive factors [e.g. IL‐1 receptor antagonist (IL‐1RA), IL‐18 binding protein (IL‐18BP) and IL‐10] contributes to the development of neuropathic pain . Moreover, research on chemokines has suggested that their systems (ligands/receptors) are involved in pathological nociceptive processes .…”

Section: Introductionmentioning

confidence: 99%

“…IL-1 receptor antagonist (IL-1RA), IL-18 binding protein (IL-18BP) and IL-10] contributes to the development of neuropathic pain. [6][7][8][9] Moreover, research on chemokines has suggested that their systems (ligands/receptors) are involved in pathological nociceptive processes. [10][11][12] Our recent results indicated that the blockade of some chemokine receptors (e.g.…”

Section: Introductionmentioning

confidence: 99%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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Summary A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up‐regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA‐1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin‐1β (IL‐1β), IL‐6 and IL‐18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid‐induced analgesia through the modulation of neuroimmune interactions.

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“…An increase in the peripheral levels of proinflammatory cytokines, changes in immune signaling pathways and a strong correlation between inflammation and peripheral neuropathy caused by chemotherapy have been observed in numerous studies [102,105,106].…”

Section: Activation Of the Immune System And Neuroinflammationmentioning

confidence: 89%

“…These mediators are able to augment proinflammatory processes and act as sensitizers for nociceptors, thus playing a crucial role in the progression of CIPN. Increased concentrations of cytokines and chemokines in the dorsal root ganglia and spinal cord induce alterations in the Schwann cells of peripheral axons, satellite cells in the dorsal root ganglia, and astrocytes in the spinal cord, which all contribute to CIPN development [102,[106][107][108][109][110][111].…”

Section: Activation Of the Immune System And Neuroinflammationmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

Sałat

2020

Pharmacol. Rep

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Background Despite the increasing knowledge of the etiology of neuropathic pain, this type of chronic pain is resistant to available analgesics in approximately 50% of patients and therefore is continuously a subject of considerable interest for physiologists, neurologists, medicinal chemists, pharmacologists and others searching for more effective treatment options for this debilitating condition. Materials and methods The present review article is the first of the two articles focused on chemotherapy-induced peripheral neuropathy (CIPN). Results CIPN is regarded as one of the most common drug-induced neuropathies and is highly pharmacoresistant. The lack of efficacious pharmacological methods for treating CIPN and preventing its development makes CIPN-related neuropathic pain a serious therapeutic gap in current medicine and pharmacotherapy. In this paper, the most recent advances in the field of studies on CIPN caused by platinum compounds (namely oxaliplatin and cisplatin), taxanes, vinca alkaloids and bortezomib are summarized. Conclusions The prevalence of CIPN, potential causes, risk factors, symptoms and molecular mechanisms underlying this pharmacoresistant condition are discussed.

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Chemokine Signaling in Chemotherapy-Induced Neuropathic Pain

Cited by 77 publications

References 115 publications

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

Cellular mechanisms and treatments for chemobrain: insight from aging and neurodegenerative diseases

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy

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