Intrathecal interleukin-10 gene therapy attenuates paclitaxel-induced mechanical allodynia and proinflammatory cytokine expression in dorsal root ganglia in rats

• Published in: Brain, behavior, and immunity Vol. 21; no. 5; pp. 686 - 698
• Main Authors: Ledeboer, Annemarie, Jekich, Brian M, Sloane, Evan M, Mahoney, John H, Langer, Stephen J, Milligan, Erin D, Martin, David, Maier, Steven F, Johnson, Kirk W, Leinwand, Leslie A, Chavez, Raymond A, Watkins, Linda R
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.07.2007
• Subjects: Allergy and Immunology; Animals; Antineoplastic Agents, Phytogenic - adverse effects; CD11b Antigen - drug effects; CD11b Antigen - metabolism; Cytokines - drug effects; Cytokines - immunology; Disease Models, Animal; Ganglia, Spinal - cytology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Genetic Therapy - methods; Glia; Hyperalgesia - chemically induced; Hyperalgesia - etiology; Hyperalgesia - prevention & control; Injections, Spinal; Interleukin-1; Interleukin-10 - administration & dosage; Interleukin-10 - genetics; Interleukin-10 - physiology; Interleukin-1beta - drug effects; Interleukin-1beta - metabolism; Macrophages; Male; Meninges; Meninges - drug effects; Meninges - metabolism; Neuroglia - drug effects; Neuroglia - metabolism; Neuropathic pain; Paclitaxel - adverse effects; Pain Threshold - drug effects; Pain Threshold - physiology; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - complications; Peripheral Nervous System Diseases - prevention & control; Plasmids - administration & dosage; Plasmids - genetics; Psychiatry; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1 - antagonists & inhibitors; Receptors, Interleukin-1 - physiology; RNA, Messenger - analysis; Spinal Cord - cytology; Spinal Cord - drug effects; Spinal Cord - metabolism; Tumor necrosis factor; Tumor Necrosis Factor-alpha - drug effects; Tumor Necrosis Factor-alpha - metabolism; Interleukin-1; Meninges; Glia; Macrophages; Tumor necrosis factor; Neuropathic pain

Abstract Paclitaxel is a commonly used cancer chemotherapy drug that frequently causes painful peripheral neuropathies. The mechanisms underlying this dose-limiting side effect are poorly understood. Growing evidence supports that proinflammatory cytokines, such as interleukin-1 (IL-1) and tumor nec...