Trichostatin A, a histone deacetylase inhibitor, reduces lesion growth and hyperalgesia in experimentally induced endometriosis in mice.

BACKGROUND The aim of this study was to evaluate the effect of trichostatin A (TSA) in a mouse model of endometriosis on serum tumour necrosis factor alpha (TNFalpha) levels, hotplate latency, lesion size and immunoreactivity to Trpv1, Pkcepsilon and Pgp9.5. METHODS We used 30 adult female mice, and endometriosis was induced by auto-transplanting pieces of uterus (ENDO) or fat (SHAM) to peritoneum in lower parts of the abdominal and pelvic cavity. Two weeks later, the ENDO group was further divided into two groups randomly: one received TSA treatments and the other received injections of dimethyl sulfoxide, as did the SHAM mice. Four weeks later, all mice were sacrificed. Response latency in hotplate test and serum TNFalpha levels were measured before the surgery, and before and after the treatment, along with the average lesion size and the immunoreactivity to Trpv1, Pkcepsilon and Pgp9.5, in both eutopic and ectopic endometrium and vaginal tissue. RESULTS We found that mice receiving TSA had a significantly reduced average lesion size as compared with untreated mice, as well as a significant improvement in response to a noxious thermal stimulus. They also had a significantly lower immunoreactivity to Trpv1 in eutopic endometrium, to Pkcepsilon in ectopic endometrium and to Pgp9.5 in vagina. CONCLUSIONS Endometriosis causes increased central sensitivity to noxious stimuli. Treatment with TSA significantly reduces lesion growth and may relieve pain symptoms in women with endometriosis, indicating that histone deacetylase inhibitors may be a promising therapeutic agent.