title: Astrocytes, but not microglia, are activated in oxaliplatin and bortezomib-induced peripheral neuropathy in the rat.
abstract: Spinal microglia are widely recognized as activated by and contributing to the generation and maintenance of inflammatory and nerve injury related chronic pain; whereas the role of spinal astrocytes has received much less attention, despite being the first glial cells identified as activated following peripheral nerve injury. Recently it was suggested that microglia do not appear to play a significant role in chemotherapy-induced peripheral neuropathy (CIPN), but in contrast astrocytes appear to have a key role. In spite of the generalizability of astrocyte recruitment across chemotherapy drugs, its correlation to the onset of the behavioral CIPN phenotype has not been determined. The astroglial and microglial markers glial fibrillary acidic protein (GFAP) and OX-42 were imaged here to examine glial reactivity in multiple models of CIPN over time and to contrast this response to that produced in the spinal nerve ligation (SNL) model. Microglia were strongly activated following SNL, but not activated at any of the time points observed following chemotherapy treatments. Astrocytes were activated following both oxaliplatin and bortezomib treatment in a manner that paralleled chemotherapy-evoked behavioral changes. Both the behavioral phenotype and activation of astrocytes were prevented by co-administration of minocycline hydrochloride in both CIPN models, suggesting a common mechanism.
authors.affiliation: The Department of Anesthesiology and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe, Unit 409, Houston, TX 77030, United States.
authors.forename: C R
authors.initials: CR
authors.lastname: Robinson
authors.affiliation: The Department of Anesthesiology and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe, Unit 409, Houston, TX 77030, United States.
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.affiliation: The Department of Anesthesiology and Pain Medicine Research, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe, Unit 409, Houston, TX 77030, United States. Electronic address: pdougherty@mdanderson.org.
authors.forename: P M
authors.initials: PM
authors.lastname: Dougherty
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D001897:Boronic Acids / Q000633:toxicity*; D000069286:Bortezomib; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000633:toxicity*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D011719:Pyrazines / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013127:Spinal Nerves / Q000293:injuries
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D009944:Organoplatinum Compounds; D011719:Pyrazines; D000077150:Oxaliplatin; D000069286:Bortezomib; D008911:Minocycline
keywords: astrocytes; bortezomib; microglia; minocycline; oxaliplatin