Estradiol replacement modifies c-fos expression at the spinomedullary junction evoked by temporomandibular joint stimulation in ovariectomized female rats

Abstract

The influence of estradiol (E2) treatment on temporomandibular joint (TMJ) nociceptive processing in the caudal trigeminal sensory brain stem complex was assessed in ovariectomized female rats by quantitative Fos-immunoreactivity (Fos-LI). After 2 days of daily injections of high (HE2) or low (LE2) dose E2 rats were anesthetized and the small fiber excitant, mustard oil (MO, 0-20%), was injected into the TMJ and after two hours later brains were processed for Fos-LI. TMJ-evoked Fos-LI in laminae I-II at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C 1-2 ) junction and the dorsal paratrigeminal region (dPa5) was significantly greater in HE2 than LE2 rats, while Fos-LI produced at the ventral trigeminal interpolaris/caudalis transition region (Vi/Vc vl ) was similar. E2 treatment also modified the influence of N-methyl-D-aspartate (NMDA) and amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor antagonists on TMJ-evoked Fos-LI. The NMDA antagonist, MK-801, dose-dependently reduced the Fos-LI response at the Vc/C 1-2 junction in HE2 rats, while only high dose MK-801 was effective in LE2 rats. MK801 reduced equally the Fos-LI response at the Vi/Vc transition in both groups, while only minor effects were seen at the dPa5 region. The AMPA receptor antagonist, NBQX, reduced Fos-LI at the Vc/C 1-2 and Vi/Vc vl regions in HE2 rats, while only high dose NBQX was effective in LE2 rats. NBQX did not reduce Fos-LI at the dPa5 region in either group. These results suggest that estrogen status plays a significant role in TMJ nociceptive processing at the Vc/C 1-2 junction mediated, in part, through ionotropic glutamate receptor-dependent mechanisms. Keywordspain; trigeminal subnucleus caudalis; NMDA receptor; AMPA receptor; mustard oil Temporomandibular muscle/joint disorders (TMJD) include a heterogeneous group of conditions that present with pain in the temporomandibular joint (TMJ) and muscles of mastication. TMJD is more prevalent in women than men (Bush, 1993;Lipton, 1993;LeResche, 1997;Huang et al., 2002) and although the basis for this sex difference is not certain, systematic variation in pain severity over the menstrual cycle suggests a role for ovarian Correspondence: Keiichiro Okamoto, D.D.S, Ph.D., Dept. of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, MN, 55455, Phone: (612) Fax: (612) 626-2651, Email: okamo007@umn.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Suenaga et al., 2001;Isselee et al., 2002;LeResche et al., 2003;Landi et al., 2005). NIH Public AccessSeveral aspects of ...

Differential ascending projections of temporomandibular joint-responsive brainstem neurons to periaqueductal gray and posterior thalamus of male and female rats

“…This pattern of Fos expression was consistent with earlier results (Bereiter 2001; Okamoto et al 2008) and confirmed that the low dose E2 regimen used here was not sufficient to enhance TMJ-evoked Fos-LI in the TBNC. Analyses of TMJ-evoked Fos-LI within individual brainstem regions found only minor sex differences (Tables 1, 2 and 3).…”

“…Sensory afferent nerves that supply the TMJ and muscles of mastication terminate at multiple rostrocaudal levels of the trigeminal brainstem nuclear complex (TBNC) and upper cervical dorsal horn (Shigenaga et al 1988; Dessem et al 2007). C-fos immunohistochemical studies have confirmed that select regions of the TBNC that receive direct input from the TMJ, e.g., dorsal paratrigeminal region (dPa5) and superficial laminae of Vc and upper cervical dorsal horn (C 1–2 ), encode the intensity of an intra-TMJ stimulus in an estrogen-dependent manner (Bereiter 2001; Okamoto et al 2008). Anatomical tract-tracing combined with c-fos methods have been used to report that TBNC neurons responsive to jaw muscle (Ikeda et al 2003; Sugiyo et al 2005) or TMJ injury (Yamazaki et al 2008) projected to higher brain centers associated with nociceptive processing; however, only male animals were included in these studies.…”

Hippocampal Nerve Growth Factor Potentiated by 17β-Estradiol and Involved in Allodynia of Inflamed TMJ in Rat

“…Evidence shows that estrogen can sensitize TMJ nociception through central trigeminal ganglion. 5,48,64 Consistently, both our Figure 3. Attenuation of mechanical allodynia of inflamed TMJ by blocking NGF in the hippocampus.…”

“…49 Many studies have been done to understand how estrogen affects peripheral and central nociceptive processes related to TMJ inflammatory pain. 5,15,24,25,47,48,64,70 However, whether estrogen enhances or decreases TMJ nociception remains controversial among these studies. Evidence shows that estrogen can sensitize TMJ nociception through central trigeminal ganglion.…”

Investigation of Characteristic Indeices Related to Temporomandibular Joint Osteoarthrosis

“…The main features of the disease are the damage and loss of the articular cartilage tissue 1) . There are two kinds of treatment methods for TMJOA.…”