Estrogen status and psychophysical stress modify temporomandibular joint input to medullary dorsal horn neurons in a lamina-specific manner in female rats

Abstract

Estrogen status and psychological stress contribute to the expression of several chronic pain conditions including temporomandibular muscle and joint disorders (TMJD). Sensory neurons that supply the temporomandibular joint (TMJ) region terminate in laminae I and V of the spinal trigeminal nucleus (Vc/C1-2 region); however, little is known about lamina specificity and environmental influences on the encoding properties of TMJ brainstem neurons. To test the hypothesis that Vc/C1-2 neurons integrate both interoceptive and exteroceptive signals relevant for TMJ nociception, we recorded TMJ-evoked activity in superficial and deep laminae of ovariectomized rats under high and low estradiol (E2) and stress conditions. Rats received daily injections of low (LE) or high (HE) dose E2 and were subjected to forced swim (FS) or sham swim conditioning for 3 days. The results revealed marked lamina specificity in that HE rats displayed enhanced TMJ-evoked activity in superficial, but not deep, laminae independent of stress conditioning. By contrast, FS conditioned rats displayed increased background firing and TMJ-evoked activity of neurons in deep, but not superficial, laminae independent of E2 status. FS also enhanced TMJ-evoked masseter muscle activity and suggested the importance of deep dorsal horn neurons in mediating evoked jaw muscle activity. In conclusion, E2 status and psychophysical stress play a significant role in modifying the encoding properties of TMJ-responsive medullary dorsal horn neurons with a marked lamina specificity.

A Clinically Relevant Animal Model of Temporomandibular Disorder and Irritable Bowel Syndrome Comorbidity

“…This same subchronic stress paradigm induced somatic thermal and chemical hypersensitivity that lasted approximately 8 days and sensitized trigeminal nucleus caudalis neurons to noxious stimulation of the temporomandibular joint 47,50,51 . The unique aspect of our model is that requisite muscle injury prior to stress transitioned the stress-induced visceral hypersensitivity from acute or transient to chronic pain, persisting at least 6 weeks.…”

“…Likewise, currently available animal models of pain arising from the viscera or the temporomandibular joint fluctuate across the estrous cycle and are sensitive to hormonal manipulation 3,9,18,31,33,37,41,47,53 . Estrogen is pronociceptive in many visceral pain models in rodents.…”

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

“…Since chronic pain and learning and memory likely share common pathways (Ji et al, 2003) and that estrogen status influences TMJ nociceptive processing (Bereiter and Okamoto, 2011), we sought to determine if group I antagonists had a differential effect on TMJ nociceptive processing under high and low estrogen conditions. Previously, we reported that the encoding properties of TMJ-responsive neurons in superficial laminae at the Vc/C 1-2 region varied over the estrous cycle in intact female rats (Okamoto et al, 2003), and matched well the results seen following high-vs. low-dose exogenous E2 treatment (Tashiro et al, 2007;Okamoto et al, 2013). Thus, it was unexpected to find that E2 status did not have a greater influence on the effectiveness of group I antagonists to inhibit TMJ nociception, although lesser effects were noted.…”

“…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.…”

Inhibition of temporomandibular joint input to medullary dorsal horn neurons by 5HT3 receptor antagonist in female rats

“…The central projections of sensory nerves that supply the TMJ region terminate mainly in the trigeminal subnucleus caudalis (Vc)/upper cervical cord (Vc/C 1–2 ) region (Jacquin et al, 1983, Takemura et al, 1987, Shigenaga et al, 1988). Previously, we reported that estrogen status (Okamoto et al, 2003, Tashiro et al, 2007) and psychophysical stress influenced the encoding properties of TMJ-responsive neurons at Vc/C 1–2 region in a lamina-specific manner (Okamoto et al, 2012, Okamoto et al, 2013). Female gender and psychological distress are risk factors for persistent TMJ pain (LeResche, 1997, Bereiter and Okamoto, 2011, Maixner et al, 2011, Slade et al, 2014).…”