Pain Fiber Anesthetic Reduces Brainstem Fos after Tooth Extraction

Abstract

We recently demonstrated that pain-sensing neurons in the trigeminal system can be selectively anesthetized by co-application of QX-314 with the TRPV1 receptor agonist, capsaicin (QX cocktail). Here we examined whether this new anesthetic strategy can block the neuronal changes in the brainstem following molar tooth extraction in the rat. Adult male Sprague-Dawley rats received infiltration injection of anesthetic 10 min prior to lower molar tooth extraction. Neuronal activation was determined by immunohistochemistry for the proto-oncogene protein c-Fos in transverse sections of the trigeminal subnucleus caudalis (Sp5C). After tooth extraction, c-Fos-like immunoreactivity (Fos-LI) detected in the dorsomedial region of bilateral Sp5C was highest at 2 hrs (p < .01 vs. naïve ipsilateral) and declined to pre-injury levels by 8 hrs. Pre-administration of the QX cocktail significantly reduced to sham levels Fos-LI examined 2 hrs after tooth extraction; reduced Fos-LI was also observed with the conventional local anesthetic lidocaine. Pulpal anesthesia by infiltration injection was confirmed by inhibition of the jaw-opening reflex in response to electrical tooth pulp stimulation. Our results suggest that the QX cocktail anesthetic is effective in reducing neuronal activation following tooth extraction. Thus, a selective pain fiber 'nociceptive anesthetic' strategy may provide an effective local anesthetic option for dental patients in the clinic.

The Role of Transient Receptor Potential (TRP) Channels in the Transduction of Dental Pain

“…TRP channels in the sensory neurons have been targeted to develop pain-specific local anesthesia in an animal study [270]. Capsaicin (a TRPV1 activator) has been combined with a permanently charged derivative of lidocaine, QX-314, and this combination appears to be effective as a local anesthetic [271,272,273]. An animal study demonstrated that local application of this drug combination in the gingiva near a tooth before extraction reduced extraction-induced neuronal activation, indicated by reduced expression of c-Fos in the brainstem trigeminal subnucleus caudalis [273].…”

“…Capsaicin (a TRPV1 activator) has been combined with a permanently charged derivative of lidocaine, QX-314, and this combination appears to be effective as a local anesthetic [271,272,273]. An animal study demonstrated that local application of this drug combination in the gingiva near a tooth before extraction reduced extraction-induced neuronal activation, indicated by reduced expression of c-Fos in the brainstem trigeminal subnucleus caudalis [273]. Eugenol was reported to sensitize and then desensitize TRPV1 channels, which may explain the pain suppressing action of zinc oxide eugenol cements used in temporary restorations of carious teeth [274].…”

Hedonic drinking engages a supraspinal inhibition of thermal nociception in adult rats

“…and were transcardially perfused sequentially with PBS (0.01 M) followed by paraformaldehyde (4% in PBS). c-fos immuno-labelling was performed according to previously published methods [8]. The lumbar spinal cord was removed for post-fixation overnight and cryopreserved in 30% sucrose for 3-4 weeks at 4°C.…”