Sexual Dimorphism on Cytokines Expression in the Temporomandibular Joint: The Role of Gonadal Steroid Hormones

Abstract

Temporomandibular joint pain-related conditions are generally characterized by local inflammation; however, little studies have focused on the role of gonadal hormones in the expression of inflammatory mediators, such as cytokines. Therefore, we asked whether gonadal steroid hormones affect formalin-induced cytokines expression in the rat temporomcandibular joint. The expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and cytokine-induced neutrophil chemoattractant (CINC)-1 was significantly higher in males than in diestrus and proestrus females and was decreased by orchiectomy and restored by testosterone replacement. The expression of IL-6 was significantly higher in diestrus and proestrus females than in males, and was decreased by ovariectomy and restored by estradiol or progesterone administration. We conclude that testosterone increases the expression of TNF-α, IL-1β and CINC-1, and estradiol and progesterone increase the expression of IL-6. New clinical approaches based on inhibition of pro-inflammatory mediators are starting to supplant traditional immunosuppressive therapies and gonadal hormones may influence their effectiveness or clinical dosage.

Estrogen in cycling rats alters gene expression in the temporomandibular joint, trigeminal ganglia and trigeminal subnucleus caudalis/upper cervical cord junction

“…In our study, we found that with increased 17β‐estradiol, IL‐8Rβ expression was upregulated and other have demonstrated that upregulation of IL‐8Rβ causes Ca 2+ ‐regulated opioid release from polymorphonuclear cells and thereby inhibits inflammatory pain (Rittner et al, 2006). In addition, studies have also shown other cytokines such as IL‐6 (Yun et al, 2008; Torres‐Chavez et al, 2010), IL‐1β and IL‐8 (Yun et al, 2008) are modulated in the TMJ tissues after estrogen administration. Our study did not observe any affect on these cytokines.…”

The role of transient receptor potential A 1 (TRPA1) in the development and maintenance of carrageenan-induced hyperalgesia

“…Cytokines measurement was performed as previously described (Torres-Chavez et al, 2011). Prior to the assay, hind paw tissue was homogenized in phosphate buffered saline (PBS, pH ¼ 7.4) containing 0.4 M NaCl, 0.05% Tween-20, 0.5% bovine serum albumin, 0.1 mM phenylmethylsulfonyl fluoride, 0.1 M benzethonium chloride, 10 mM EDTA and 20 kl/mL aprotinin.…”

Pain Perception during Menstrual Cycle

“…In ovariectomized rats, amygdala implant of both progesterone and estradiol heightened the responsiveness to colorectal distension, suggesting a central modulation of visceral pain induced by female hormones [13]. Moreover, both female hormones modulate mediators such as cytokines in the rat temporomandibular joint (TMJ) [14]. In analogy with estrogens, progesterone showed both pronociceptive and antinociceptive effect, given that it was able to reduce allodynia in neuropathic pain after spinal cord injury [15], but increased hyperalgesia in male and ovariectomized female rats [16].…”