Abstract
Chronic pain is a major symptom in patients with endometriosis, a common gynecologic
condition affecting women in their reproductive years. Although many proalgesic substances
are produced by endometriosis lesions, experimental evidence supporting their relative
roles is still lacking. Furthermore, it is unclear whether these proalgesic agents
directly activate nociceptors to induce endometriosis pain. To determine their relative
contribution to pain associated with endometriosis, we evaluated the intrathecal administration
of oligodeoxynucleotides (ODNs) antisense to messenger RNA for receptors for 3 pronociceptive
mediators known to be produced by the ectopic endometrium. Two weeks after the implant
of autologous uterine tissue onto the gastrocnemius muscle, local mechanical hyperalgesia
was observed in operated rats. Intrathecal antisense ODN targeting messenger RNA for
the interleukin 6 receptor–signaling complex subunit glycoprotein 130 and the nerve
growth factor tyrosine kinase receptor A, but not their mismatch ODNs, reversibly
attenuated mechanical hyperalgesia at the implant site. In contrast, intrathecal antisense
ODN targeting the tumor necrosis factor receptor 1, at a dose that markedly inhibited
intramuscularly injected tumor necrosis factor alpha, had only a small antihyperalgesic
effect in this model. These results indicate the relative contribution of pronociceptive
mediators produced by ectopic endometrial tissue to endometriosis pain. The experimental
approach presented here provides a novel method to evaluate for the differential contribution
of mediators produced by other painful lesions as well as endometriosis lesions as
targets for novel treatment of pain syndromes.
Perspective
This article presents evidence for the relative contribution of proalgesic mediators
to primary hyperalgesia displayed by rats submitted to a model of endometriosis pain.
This approach can be used to identify potential targets for the treatment of endometriosis
pain.
Key words
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Article info
Publication history
Published online: April 21, 2014
Accepted:
April 8,
2014
Received in revised form:
April 1,
2014
Received:
January 23,
2014
Footnotes
Funded by the National Institutes of Health.
The authors report no biomedical financial interests or potential conflicts of interest.
Identification
Copyright
© 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.
