Fibromyalgia (FM) is a syndrome characterized by
chronic pain with depression as a frequent comorbidity. However, efficient management of the
pain and depressive symptoms of FM is lacking. Given that endogenous
oxytocin (OXT) contributes to the regulation of
pain and
depressive disorders, herein, we investigated the role of OXT in an experimental
reserpine-induced FM model. In FM model, OXT-monomeric
red fluorescent protein 1 (OXT-mRFP1) transgenic rats exhibited increased depressive behavior and sensitivity in a mechanical nociceptive test, suggesting reduced
pain tolerance. Additionally, the development of the FM-like phenotype in OXT-mRFP1 FM model rats was accompanied by a significant reduction in OXT
mRNA expression in the magnocellular neurons of the paraventricular nucleus. OXT-mRFP1 FM model rats also had significantly fewer
tryptophan hydroxylase (TPH)- and
tyrosine hydroxylase (TH)-immunoreactive (ir) neurons as well as reduced
serotonin and
norepinephrine levels in the dorsal raphe and locus coeruleus. To investigate the effects of stimulating the endogenous OXT pathway, rats expressing OXT-human
muscarinic acetylcholine receptor (hM3Dq)-mCherry designer receptors exclusively activated by
designer drugs (DREADDs) were also assessed in the FM model. Treatment of these rats with
clozapine-N-oxide (CNO), an hM3Dq-activating
drug, significantly improved characteristic FM model-induced pathophysiological
pain, but did not alter depressive-like behavior. The chemogenetically induced effects were reversed by pre-treatment with an OXT receptor antagonist, confirming the specificity of action via the OXT pathway. These results indicate that endogenous OXT may have
analgesic effects in FM, and could be a potential target for effective
pain management strategies for this disorder.