The aim of this study was to investigate whether astroglia in the medullary dorsal horn (trigeminal spinal subnucleus caudalis; Vc) may be involved in orofacial neuropathic pain following trigeminal nerve injury. The effects of intrathecal administration of the astroglial aconitase inhibitor sodium fluoroacetate (FA) were tested on Vc astroglial hyperactivity [as revealed by glial fibrillary acid protein (GFAP) labeling], nocifensive behavior, Vc extracellular signal-regulated kinase phosphorylation (pERK), and Vc neuronal activity in inferior alveolar nerve-transected (IANX) rats. Compared with sham-control rats, a significant increase occurred in GFAP-positive cells in ipsilateral Vc at postoperative day 7 in IANX rats, which was prevented following FA administration. FA significantly increased the reduced head withdrawal latency to high-intensity heat stimulation of the maxillary whisker pad skin in IANX rats, although it did not significantly affect the reduced escape threshold to low-intensity mechanical stimulation of the whisker skin in IANX rats. FA also significantly reduced the increased number of pERK-like immunoreactive cells in Vc and the enhanced Vc nociceptive neuronal responses following high-intensity skin stimulation that were documented in IANX rats, and glutamine administration restored the enhanced responses. These various findings provide the first documentation that astroglia is involved in the enhanced nociceptive responses of functionally identified Vc nociceptive neurons and in the associated orofacial hyperalgesia following trigeminal nerve injury.

To define the somatotopic arrangement of neurons in the trigeminal spinal subnucleus caudalis and upper cervical cord activated by acute noxious stimulation of various orofacial sites, pERK expression was analyzed in these neurons. After capsaicin injection into the tongue, lower gum, upper and lower lips, or mental region, pERK-like immunoreactive (pERK-LI) cells were distributed mainly in the dorsal half of the trigeminal spinal nucleus interporalis (Vi) and caudalis (Vc) transition zone (Vi/Vc zone), middle Vc, and Vc and upper cervical cord transition zone (Vc/C2 zone). pERK-LI cells were distributed throughout the dorsal to ventral portion of the Vi/Vc zone, middle Vc, and Vc/C2 zone following capsaicin injection into the anterior hard palate, upper gum, buccal mucosa, or vibrissal pad and in the ventral portion of the Vi/Vc zone, middle Vc, and Vc/C2 zone following snout, ophthalmic, or ocular injection of capsaicin. The rostrocaudal distribution area of pERK-LI cells was more extensive from the Vi/Vc zone to the Vc/C2 zone after intraoral injection than that after facial injection, and the rostrocaudal distribution of pERK-LI cells from the Vi/Vc zone to the Vc/C2 zone had a somatotopic arrangement, with the snout being represented most rostrally and ophthalmic, ocular, or mental regions represented most caudally. These findings suggest that the pERK-LI cells expressed from the Vi/Vc zone to the Vc/C2 zone following injection of capsaicin in facial and intraoral structures may be differentially involved in pain perception in facial and intraoral sites.

Burning mouth syndrome (BMS) is a chronic oro-facial pain disorder of unknown cause. It is more common in peri-and post-menopausal women, and sex hormone dysregulation is believed to be an important causative factor. Psychosocial events often trigger or exacerbate symptoms, and persons with BMS appear to be predisposed towards anxiety and depression. Atrophy of small nerve fibres in the tongue epithelium has been reported, and potential neuropathic mechanisms for BMS are now widely investigated. Historically, BMS was thought to comprise endocrinological, psychosocial and neuropathic components. Neuroprotective steroids and glial cell line-derived neurotrophic factor family ligands may have pivotal roles in the peripheral mechanisms associated with atrophy of small nerve fibres. Denervation of chorda tympani nerve fibres that innervate fungiform buds leads to alternative trigeminal innervation, which results in dysgeusia and burning pain when eating hot foods. With regard to the central mechanism of BMS, depletion of neuroprotective steroids alters the brain network-related mood and pain modulation. Peripheral mechanistic studies support the use of topical clonazepam and capsaicin for the management of BMS, and some evidence supports the use of cognitive behavioural therapy. Hormone replacement therapy may address the causes of BMS, although adverse effects prevent its use as a first-line treatment. Selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) may have important benefits, and well-designed controlled studies are expected. Other treatment options to be investigated include brain stimulation and TSPO (translocator protein 18 kDa) ligands. K E Y W O R D Sburning mouth syndrome, central pain modulation, menopause, neuroprotective steroids | 575 IMAMURA et Al. | INTRODUC TI ONBurning mouth symptoms that occurred as secondary phenomena attributable to local conditions 1-9 were previously referred to as "secondary" burning mouth syndrome (BMS), 10 but BMS now refers only to burning symptoms not attributable to local or systemic causes. 11 After excluding such conditions, some common characteristics of BMS are important. Burning sensations are usually bilateral, and intensity fluctuates. 2 The most common site is the tip of the tongue, but pain is often noted at the lateral border of the tongue, lips and hard palate. 12 Affected persons often complain of dysgeusia, 13 which may be accompanied by subjective xerostomia. 14 Peri-and post-menopausal women are predisposed to the condition.Some patients exhibit depressive symptoms and anxiety 15-18 and may express concern regarding the presence of a malignant condition. 10,16 Psychosocial stressors can trigger or worsen pain, 15,19 while eating and drinking usually alleviate pain. 10,20 These manifestations are characteristic features of BMS and should not be excluded as secondary signs or symptoms of primary disease. Agreement on these clinical features yields important clues in understanding the underlying pathoph...

It has been reported that the anterior cingulate cortex (ACC) has a variety of functions relating to pain as well as pain perception. However, the underlying mechanisms for those functions remain unclear. To elucidate the functional role of the ACC in pain perception and pain-related functions such as attention to pain and escape from pain, single neuronal activity was recorded from the ACC, and the behavioral correlates of this neuronal activity was studied. A total of 667 neurons were recorded from the ACC in awake behaving monkeys. Twenty-one had modulated activity during a heat-detection task. Eighteen of these increased their firing frequency following an increase in stimulus temperature, whereas three of them had decreased firing during heating of the face. Seventy-five percent of heat-evoked responses of heat-responsive ACC neurons were significantly depressed when monkeys detected the change in magnitude of illumination of a light presented on the front panel. The neuronal activity was significantly higher when monkeys escaped from a noxious heat stimulus than when the monkeys detected a small change in temperature (T2) above a larger initial shift (T1). No relationship between firing frequency and detection latency of the T2 stimulation was observed. These findings suggest that ACC nociceptive neurons are involved in attention to pain and escape from pain but not in the sensory discriminative aspect of pain.

This study was conducted to assess the psychological characteristics of, and determine the effectiveness of group cognitive-behavioral (CB) treatment for, patients with burning mouth syndrome (BMS). The baseline characteristics of 24 female patients (age 69.7 ± 5.9 years) and an identical number of healthy female control subjects (age 69.2 ± 5.5 years) were compared. The patient group had significantly higher anxiety scores (P < 0.05) at baseline. A brief group CB intervention was delivered in a small-group format. Two sessions were planned 6 months apart. A numeric rating scale (NRS) was used to assess pain intensity. Anxiety was evaluated using a state and trait anxiety inventories. Present pain intensity decreased after both the first and second sessions. The session effect was significant (P = 0.02), but no repeat effect was found (P = 0.19). The state anxiety inventory score also decreased after the second session. The session effect was significant (P < 0.01), as was the repeat effect (P < 0.01). The trait anxiety inventory score decreased after the second session, and the session effect was significant (P = 0.013), but the repeat effect was not (P = 0.93). The results suggest that a brief group CB intervention reduces pain intensity and anxiety in patients with BMS. (J Oral Sci 55, 17-22, 2013)