We hypothesized a role for the dysregulation of adenosine kinase (ADK) in spinal cord. The mechanisms initiated in astrocytes responsible for establishing CINP remain elusive. However the underlying mechanisms that drive these pathways and the molecular pathways engaged by A 3AR agonism remain to be defined.Īstrocytes in the spinal cord are emerging as the predominant cellular agent in establishing CINP unlike in other types of neuropathic pain where both astrocyte and microglial cell activation contribute to neuropathological processes. We have recently reported that highly selective A 3 adenosine receptor (AR) agonists block and reverse CINP, suggesting that chemotherapy causes the dysregulation of adenosine signaling at this receptor subtype. Peripheral neuropathological changes in response to chemotherapeutics are considered the provocative processes for the development of CINP however neuropathological changes within the CNS are critical for establishing the chronic pain state. Finding novel therapies for these patients are hampered by our poor understanding of the cellular and molecular mechanisms involved. CINP can linger for years and greatly impacts a patient’s quality of life due to inadequate pain management with currently available analgesics. CINP can occur in up to 60% of patients receiving oxaliplatin, which is used as a first-line chemotherapeutic for treatment of colorectal cancer. The development of chemotherapy-induced neuropathic pain (CINP) is a major dose limiting neurotoxicity created by widely used chemotherapeutic agents, including the platinum-based drug, oxaliplatin.
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