Decreased face primary motor cortex (face-M1) excitability induced by noxious stimulation of the rat molar tooth pulp is dependent on the functional integrity of medullary astrocytes.

Abstract

We have recently shown that application of the small-fiber excitant and inflammatory irritant mustard oil (MO) to the rat molar tooth pulp can decrease face-M1 excitability, but increase the excitability of trigeminal medullary dorsal horn (MDH) nociceptive neurons and that application of the astrocytic inhibitor methionine sulfoximine (MSO) to the face-M1 or MDH can attenuate the MO-induced changes. The present study aimed to determine whether medullary MSO application could modulate the MO-induced decreased face-M1 excitability. Under ketamine general anesthesia, electromyographic (EMG) electrodes were implanted into the right anterior digastric (RAD, jaw-opening muscle) of adult male Sprague-Dawley rats. A microelectrode was positioned at a low-threshold (≤30 μA) site in the left face-M1. Then MO (n = 16) or control-solution (n = 16) was applied to the previously exposed molar tooth pulp, and intracortical microstimulation threshold intensities for evoking RAD EMG activities were monitored for 15 min. MSO (0.1 mM, n = 8) or phosphate-buffered saline (PBS, n = 8) was then applied to the MDH and RAD thresholds monitored every 15 min for 120 min. Statistics used ANOVA followed by post hoc Bonferroni as appropriate (p < 0.05). As compared to baseline, RAD thresholds significantly increased (i.e., decreased excitability) within 1 min (26.3 ± 7.9%, p = 0.007) and peaked at 15 min following pulpal MO application (49.9 ± 5.7%, p < 0.001) but not following control-solution. Following MSO (but not PBS) application to the medulla, RAD thresholds significantly decreased within 15 min (26.5 ± 3.0%, p = 0.05) and at 60 min approached 6.3 ± 2.4%, of baseline values (p = 0.1). These novel findings suggest that clinically related motor disturbances arising from dental pain may involve decreased face-M1 excitability that is modulated by medullary astrocytes.