title: Role of meningeal mast cells in intrathecal morphine-evoked granuloma formation.
abstract: BACKGROUND
  Intrathecal morphine forms granulomas that arise from the adjacent arachnoid membrane. The authors propose that these inflammatory cells exit the meningeal vasculature secondary to meningeal mast cell degranulation.
  
  
  METHODS
  Three sets of experiments were accomplished in dogs: (1) ex vivo meningeal mast cell degranulation (histamine release was measured ex vivo from canine dura incubated with opiates); (2) in vivo cutaneous mast cell degranulation (flare areas on the dog abdomen were measured after subcutaneous opiates); and (3) in vivo granuloma pharmacology. Dogs with lumbar intrathecal catheters received infusion of intrathecal saline or intrathecal morphine. Intrathecal morphine dogs received (1) no other treatment (control); (2) twice-daily subcutaneous naltrexone; (3) intrathecal co-infusion of cromolyn; or (4) twice-daily subcutaneous cromolyn for the 24- to 28-day study course.
  
  
  RESULTS
  Morphine but not fentanyl evoked dural histamine release, which was blocked by cromolyn but not naloxone. Wheal/flare was produced by subcutaneous morphine, methadone, hydromorphone, but not fentanyl, and was unaffected by naltrexone but prevented by cromolyn. Granulomas occurred in all dogs receiving intrathecal morphine (15 of 15); subcutaneous naltrexone had no effect on granulomas (six of six) but was reduced by concurrent intrathecal cromolyn (zero of five) or twice-daily subcutaneous cromolyn (one of five).
  
  
  CONCLUSIONS
  The pharmacology of cutaneous/dural mast cell degranulation and intrathecal granulomas are comparable, not mediated by opioid receptors, and reduced by agents preventing mast cell degranulation. If an agent produces cutaneous mast cell degranulation at concentrations produced by intrathecal delivery, the agent may initiate granulomas.
authors: Anesthesiology Research, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0818, USA. tyaksh@ucsd.edu
authors: Tony L
authors: TL
authors: Yaksh
authors: Jeffery W
authors: JW
authors: Allen
authors: Samantha L
authors: SL
authors: Veesart
authors: Kjersti A
authors: KA
authors: Horais
authors: Shelle A
authors: SA
authors: Malkmus
authors: Miriam
authors: M
authors: Scadeng
authors: Joanne J
authors: JJ
authors: Steinauer
authors: Steve S
authors: SS
authors: Rossi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D004285:Dogs; D005260:Female; D006099:Granuloma / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006636:Histamine Release / Q000187:drug effects / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000473:pathology*; D008578:Meninges / Q000187:drug effects* / Q000473:pathology; D009020:Morphine / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D009020:Morphine