title: The effects of minocycline or riluzole treatment on spinal root avulsion-induced pain in adult rats.
abstract: Spinal root avulsion produces tactile and thermal hypersensitivity, neurodegeneration, and microglial and astrocyte activation in both the deafferented and the adjacent intact spinal cord segments. Following avulsion of the fifth lumbar spinal root, immediate and prolonged treatment with riluzole or minocycline for 2 weeks altered the development of behavioral hypersensitivity. Riluzole delayed the onset of thermal and tactile hypersensitivity and partially reversed established pain behavior. Minocycline effectively prevented and reversed both types of behavioral change. Histologic analysis revealed that both drugs reduced microglial staining in the spinal cord, with minocycline being more effective than riluzole. Astrocyte activation was ameliorated to a lesser extent. Surprisingly, neither drug provided a neuroprotective effect on avulsed motoneurons.
  
  
  CONCLUSIONS
  Immediate treatment of spinal root avulsion injuries with minocycline or riluzole prevents the onset of evoked pain hypersensitivity by reducing microglial cell activation. When treatment is delayed, minocycline, but not riluzole, reverses pre-established hypersensitivity. Thus, these drugs may provide a new translational treatment option for chronic avulsion injury pain.
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom. Electronic address: dc501@cam.ac.uk.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Chew
authors.affiliation: Peripheral Nerve Injury Unit, Royal National Orthopaedic Hospital, London, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Carlstedt
authors.affiliation: Centre for Neuroscience and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Shortland
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007839:Functional Laterality; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology; D008297:Male; D008911:Minocycline / Q000494:pharmacology / Q000627:therapeutic use; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000209:etiology*; D017288:Pain Threshold / Q000187:drug effects; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019782:Riluzole / Q000494:pharmacology / Q000627:therapeutic use*; D013119:Spinal Cord Injuries / Q000150:complications*; D013126:Spinal Nerve Roots / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D019782:Riluzole; D010751:Phosphopyruvate Hydratase; D008911:Minocycline
keywords: Avulsion; minocycline; pain; riluzole; spinal cord