Spatiotemporal profiles of dental pulp nociception in rat cerebral cortex: An optical imaging study

Abstract

Somatosensation is topographically organized in the primary (S1) and secondary somatosensory cortex (S2), which contributes to identify the region receiving sensory inputs. However, it is still unknown how somatosensory inputs from the oral region, especially nociceptive inputs from the teeth, are processed in the somatosensory cortex. We performed in vivo optical imaging and identified the precise cortical regions responding to electrical stimulation of the maxillary and mandibular dental pulp in rats. Electrical stimulation of the mandibular incisor pulp evoked neural excitation in two areas: the most rostroventral part of S1, and the ventral part of S2 caudal to the middle cerebral artery. Maxillary incisor pulp stimulation initially evoked responses only in the ventral part of S2, although later maximum responses were also observed in S1 similar to mandibular incisor stimulation responses. The maxillary and mandibular molar pulp-responding regions were located in the most ventral S2, a part of which was histologically classified as the insular oral region (IOR). In terms of the initial responses, maxillary incisor and molar stimulation induced excitation in the S2/IOR rostral to the mandibular dental pulp-responding region. Contrary to the spatially segregated initial responses, the maximum excitatory areas responding to both incisors and molars in the mandible and maxilla overlapped in S1 and the S2/IOR. Multielectrode extracellular recording supported the characteristic localization of S2/IOR neurons responding to mandibular and maxillary molar pulp stimulation. The discrete and overlapped spatial profiles of initial and maximum responses, respectively, may characterize nociceptive information processing of dental pain in the cortex.

Neural mechanisms of nociception during orthodontic treatment

“…Horinuki et al (17) reported that, in addition to S1, the cortical area caudally adjacent to the middle cerebral artery responds to electrical stimulation of maxillary and mandibular incisor and molar PDL. These anatomical findings indicate that the area corresponds to the secondary somatosensory cortex (S2) and oral region of the IC (IOR), as reported by Nakamura et al (49). S2/IOR receives varied somatosensory information from oral regions, including PDL sensation, gustation (50)(51)(52), and nociception (49,53,54).…”

“…These anatomical findings indicate that the area corresponds to the secondary somatosensory cortex (S2) and oral region of the IC (IOR), as reported by Nakamura et al (49). S2/IOR receives varied somatosensory information from oral regions, including PDL sensation, gustation (50)(51)(52), and nociception (49,53,54). Interestingly, electrical stimulation of S2/IOR induces rhythmic jaw movement (55,56).…”

Opposite effects of mu and delta opioid receptor agonists on excitatory propagation induced in rat somatosensory and insular cortices by dental pulp stimulation

“…We consider that this application method allows the drugs to penetrate at least into the superficial layers (layers I-III), where application of voltage-sensitive dyes via the same method shows a sufficient penetration, as described in our previous study [8,25]. In addition, the same method for application of 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) effectively suppresses excitatory propagation in the cortex [25], indicating a sufficient blockade of AMPA receptors.…”

“…Next, we examined the effects of MOR, DOR, or KOR activation on excitatory propagation in S2/IOR in response to the maxillary molar pulp stimulation [7,8].…”

“…Stimulation of the agranular IC, the ventral part of the IC, suppresses nociceptive responses via modulating neural activities of the dorsal raphe nucleus, periaqueductal gray, and parabrachial nucleus [5]. In terms of orofacial nociception, the insular oral region (IOR) and the dorsally adjacent secondary somatosensory cortex (S2), which are located caudal to the middle cerebral artery (MCA) in the rat, respond to electrical stimulation of dental pulps [6,7,8] or periodontal ligaments [9,10]. S2/IOR is likely to encode the strength of nociception because the amplitude of excitation in S2/IOR is dependent on the intensity of molar pulp stimulation [7].…”