Differential Effects of Estradiol on Encoding Properties of TMJ Units in Laminae I and V at the Spinomedullary Junction in Female Rats

Abstract

Tashiro A, Okamoto K, Milam SB, Bereiter DA. Differential effects of estradiol on encoding properties of TMJ units in laminae I and V at the spinomedullary junction in female rats. J Neurophysiol 98: 3242-3253, 2007. First published October 10, 2007 doi:10.1152/jn.00677.2007. To determine whether estrogen status modulated dorsal horn neural activity relevant to temporomandibular joint (TMJ) processing single units were recorded in superficial and deep laminae at the trigeminal subnucleus caudalis/upper cervical cord (Vc/C1-2) junction of ovariectomized (OvX) female rats under barbiturate anesthesia after 17␤-estradiol (E2) treatment for 2 days. E2 dose-dependently enhanced the response to intra-TMJ stimulation by adenosine triphosphate (ATP) of neurons classified as nociceptive specific (NS), but not wide dynamic range (WDR), in superficial laminae. ATP caused similar responses among NS and WDR neurons from deep laminae in all groups. By contrast, the cutaneous receptive field areas of WDR, but not NS, units in superficial and deep laminae were enlarged in high E2-treated (HE2) compared with low E2-treated (LE2) females. Units from untreated or vehicle-treated male rats displayed responses similar to those of LE2 females. TMJ units in superficial laminae from females were more likely to receive convergent cutaneous input and respond to jaw movement than males, independent of E2 treatment. Western blot analysis revealed similar levels of P2X2 and P2X3 receptor protein in Vc/C1-2 or trigeminal ganglion samples in all groups. Immunohistochemistry revealed dense terminal labeling for P2X3 receptors in superficial laminae and moderate labeling in deep laminae at the Vc/C1-2 junction. These data indicated a significant linkage between estrogen status and the magnitude of articular input evoked by ATP from TMJ neurons in the superficial laminae at the Vc/C1-2 junction, whereas estrogenic modulation of TMJ neurons in deep laminae affected only the convergent input from overlying facial skin.

Emerging Peripheral Receptor Targets for Deep-tissue Craniofacial Pain Therapies

“…While this finding is consistent with the observation that greater pain is present when estrogen is low, more prolonged exposure of DRG neurons to estradiol apparently does not affect P2X currents (Xu et al, 2008). Trigeminal ganglion neurons, however, do possess estrogen receptors (Bereiter et al, 2005), and estradiol modulates the responses of brainstem neurons evoked by injection of ATP into the jaw joint (Tashiro et al, 2007).…”

Local group I mGluR antagonists reduce TMJ-evoked activity of trigeminal subnucleus caudalis neurons in female rats

“…1B). The total response to ATP (i.e., total Rmag) prior to drug application was significantly greater in units from HE than LE rats (632 ± 99 vs. 261 ± 31 vs. spikes/stimulus, respectively, F 1,30 = 13.1, p < 0.005) and was consistent with our previous results (Tashiro et al, 2007).…”

“…Previously, we determined that the response properties of TMJ neurons in the superficial laminae at the Vc/C 1-2 region varied over different stages of the estrous cycle in intact female rats (Okamoto et al, 2003). Furthermore, systemic administration of estradiol (E2) for 2 days (Tashiro et al, 2007;Okamoto et al, 2013) or acute local application (Tashiro et al, 2012) significantly altered TMJ-evoked activity of Vc/C 1-2 neurons in ovariectomized (OvX) female rats in a dose-related manner.…”

Estrogenic influences in pain processing

“…The results clearly suggest that a total lack of estrogens enhances pro-nociceptive mechanisms in the trigeminal system. This is further supported by studies showing enhanced sensitization of neurons in the trigeminal subnucleus caudalis during late proestrus and estrus when estrogen levels decline abruptly (Martin et al, 2007), and a significant dose-dependent influence of estradiol (daily subcutaneous injections of 2 g or 20 g estradiol for three days) on the encoding properties of the nociceptivespecific neurons in lamina I-II in the medullary dorsal horn of ovariectomized female rats (Tashiro et al, 2007). The neurons in laminae I-II at the subnucleus caudalis/C2-junction have been shown to play a critical role in mediating sex differences related to temporomandibular pain (Bereiter, 2001;Bereiter and Okamoto, 2011).…”