02391nas a2200385   4500000000100000008004100001260001300042653001200055653002100067653001900088653000900107653002400116653004500140653002700185653002100212653002200233653000900255653002900264653001500293100001100308700001500319700001100334700001300345700001300358700001300371700001500384700001200399700001500411700001200426245010600438300001100544490000800555520142800563022001401991       2006                            d  c2006 Mar10aAnimals10aBehavior, Animal10aDNA, Bacterial10aMice10aMice, Inbred BALB C10aMycobacterium Infections, Nontuberculous10aMycobacterium ulcerans10aPain Measurement10aPeripheral nerves10aSkin10aSkin Diseases, Bacterial10aSkin Ulcer1 aGoto M1 aNakanaga K1 aAung T1 aHamada T1 aYamada N1 aNomoto M1 aKitajima S1 aIshii N1 aYonezawa S1 aSaito H00aNerve damage in Mycobacterium ulcerans-infected mice: probable cause of painlessness in buruli ulcer.  a805-110 v1683 a<p>Buruli ulcer is an emerging chronic painless skin disease found in the tropics and caused by Mycobacterium ulcerans; however, it remains unknown why the large and deep ulcers associated with this disease remain painless. To answer this question, we examined the pathology of BALB/c mice inoculated in the footpads with M. ulcerans African strain 97-107. On days 54 to 70 after inoculation, extensive dermal ulcers, subcutaneous edema, and numerous acid-fast bacilli were noted at the inoculate region. Nerve invasion occurred in the perineurium and extended to the endoneurium, and some nerve bundles were swollen and massively invaded by acid-fast bacilli. However, Schwann cell invasion, a characteristic of leprosy, was not observed. Vacuolar degeneration of myelin-forming Schwann cells was noted in some nerves which may be induced by mycolactone, a toxic lipid produced by M. ulcerans. Polymerase chain reaction analysis of microdissected nerve tissue sections showed positive amplification of M. ulcerans-specific genomic sequences but not of Mycobacterium leprae-specific sequences. Behavioral tests showed decrease of pain until edematous stage, but markedly ulcerated animals showed ordinary response against stimulation. Our study suggests that the painlessness of the disease may be partly due to intraneural invasion of bacilli. Further studies of nerve invasion in clinical samples are urgently needed.</p>  a0002-9440