title: Chronic morphine increases Fos-positive neurons after concurrent cornea and tail stimulation.
abstract: OBJECTIVE
  The aim of the present study was to examine the effect of chronic morphine exposure on diffuse noxious inhibitory controls in a large population of neurons throughout the medullary dorsal horn, as assessed using immunocytochemistry for c-Fos protein.
  
  
  BACKGROUND
  Overuse of medications, including the opioids, to treat migraine headache can lead to progressively more frequent headaches. In addition, chronic daily headache sufferers and chronic opioid users both lack the inhibition of pain produced by noxious stimulation of a distal body region, often referred to as diffuse noxious inhibitory controls.
  
  
  METHODS
  In urethane anesthetized rats, Fos-positive neurons were quantified in chronic morphine and vehicle-treated animals following 52°C noxious thermal stimulation of the cornea with and without the application of a spatially remote noxious stimulus (placement of the tail in 55°C water).
  
  
  RESULTS
  When compared to chronic morphine-treated animals that did not receive the spatially remote noxious stimulus, chronic morphine-treated animals given corneal stimulation along with the spatially remote noxious stimulus demonstrated a 163% increase (P < .05) in the number of Fos-positive neurons in the superficial laminae of the medullary dorsal horn and a 682% increase (P < .01) in deep laminae that was restricted to the side ipsilateral to the applied stimulus. In contrast, no significant difference was found in Fos-like immunoreactivity in vehicle-treated animals given concurrent cornea and tail stimulation or only cornea stimulation in either superficial or deep laminae.
  
  
  CONCLUSIONS
  It is proposed that an increase in descending facilitation and subsequent loss of diffuse noxious inhibitory controls contributes to the development of medication overuse headache.
authors.affiliation: Department of Biomedical Sciences, College of Osteopathic Medicine, University of New England, Biddeford, ME, USA.
authors.forename: Ashlee
authors.initials: A
authors.lastname: Robbins
authors.forename: David
authors.initials: D
authors.lastname: Schmitt
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Winterson
authors.forename: Ian D
authors.initials: ID
authors.lastname: Meng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003315:Cornea / Q000294:innervation; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008526:Medulla Oblongata / Q000473:pathology; D009020:Morphine / Q000008:administration & dosage*; D009294:Narcotics / Q000008:administration & dosage*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D016761:Oncogene Proteins v-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013623:Tail / Q000294:innervation
chemical_list: D009294:Narcotics; D016761:Oncogene Proteins v-fos; D009020:Morphine