Activation of spinal microglia in a murine model of peripheral inflammation-induced, long-lasting contralateral allodynia.
Increased sensitivity contralateral to an injury has been described in humans and in various models of neuropathic pain in rats. The mechanism underlying contralateral hypersensitivity is as yet unclear, although previous studies have implicated involvement of both spinal neurons and glia. We describe the development of a temporally delayed, robust and long-lasting contralateral allodynia in mice after hindpaw injection with 4% carrageenan. Both ipsilateral and contralateral allodynia could be inhibited temporarily by intrathecally administered morphine, clonidine, or neostigmine. The delayed development of contralateral allodynia correlated with an increase in OX-42, but not GFAP immunoreactivity in the contralateral dorsal horn. Furthermore, intrathecal treatment with minocycline inhibited the development of contralateral allodynia, suggesting that microglial activation plays a key role in contralateralization, and may be a potential target for clinical intervention after injury or inflammation has occurred, to eliminate the subsequent development of extraterritorial pain.
Department of Anesthesiology, University of Minnesota, 321 Church Street, Minneapolis, MN 55455, United States. schr0332@umn.edu
Kristin L
KL
Schreiber
Alvin J
AJ
Beitz
George L
GL
Wilcox
D000700:Analgesics / Q000627:therapeutic use; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D002351:Carrageenan; D004195:Disease Models, Animal; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D017288:Pain Threshold / Q000187:drug effects; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology*; D013997:Time Factors
D000700:Analgesics; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D002351:Carrageenan