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 face-M1 astrocytes.

Acute inflammatory dental pain is a prevalent condition often associated with limited jaw movements. Mustard oil (MO, a small-fiber excitant/inflammatory irritant) application to the rat molar tooth pulp induces increased excitability (i.e., central sensitization) of trigeminal medullary dorsal horn (MDH) nociceptive neurons that can be modulated by MDH application of the astrocytic inhibitor methionine sulfoximine (MSO). The objectives of the study were to determine whether MO application to the rat right maxillary first molar tooth pulp affects left face-M1 excitability manifested as altered intracortical microstimulation thresholds for evoking electromyographic activity in the right anterior digastric (RAD, jaw-opening muscle), and whether MSO application to face-M1 can modulate this MO effect. Under Ketamine general anesthesia, Sprague-Dawley male rats had a microelectrode positioned at a low-threshold (≤30 µA) face-M1 site. Then MO (n = 16) or control solution (n = 16) was applied to the previously exposed tooth pulp, and RAD threshold was monitored for 15 min. MSO (0.1 mM, n = 8) or saline (n = 8) was then applied to the face-M1, and RAD thresholds were monitored every 15 min for 120 min. ANOVA followed by post hoc Bonferroni was used to analyze data (p < 0.05). Within 15 min of MO (but not control) pulp application, RAD thresholds increased significantly (p < 0.001) as compared to baseline. One hour following MSO (but not saline) application to the face-M1, RAD thresholds decreased significantly (p = 0.005) toward baseline. These novel findings suggest that acute inflammatory dental pain is associated with decreased face-M1 excitability that may be dependent on the functional integrity of face-M1 astrocytes and related to mechanisms underlying limited jaw movements in acute orofacial pain conditions.

Suppressive effects of D-glucosamine on the 5-HT sensitive nociceptive units in the rat tooth pulpal nerve.

It is well known that D-glucosamine hydrochloride (DGL) has a variety of biological activities and is regarded as a nutritional supplement effective in improving various disorders, including osteoarthritis and atherosclerosis. Although it has been reported that DGL has a significant pain relief effect in treating osteoarthritis, little is known about the characteristics of the effects of this compound on dental pain. The present study was undertaken to evaluate the applicability of DGL as a medicament to control pulpalgia. Using an in vitro rat mandible-inferior alveolar nerve preparation (jaw-nerve preparation), we evaluated the effects of DGL on 5-hydroxytryptamine (5-HT) sensitive nociceptive responses in the tooth pulpal nerve. 5-HT-induced nociceptive responses were fairly suppressed by direct application of DGL, suggesting that DGL have a pain relief effect on patients with dental pain.

Effect of massage on the efficacy of the mental and incisive nerve block.

The purpose of this trial was to assess the effect of soft tissue massage on the efficacy of the mental and incisive nerve block (MINB). Thirty-eight volunteers received MINB of 2.2 mL of 2% lidocaine with 1 : 80,000 epinephrine on 2 occasions. At one visit the soft tissue overlying the injection site was massaged for 60 seconds (active treatment). At the other visit the crowns of the mandibular premolar teeth were massaged (control treatment). Order of treatments was randomized. An electronic pulp tester was used to measure pulpal anesthesia in the ipsilateral mandibular first molar, a premolar, and lateral incisor teeth up to 45 minutes following the injection. The efficacy of pulp anesthesia was determined by 2 methods: (a) by quantifying the number of episodes with no response to maximal electronic pulp stimulation after each treatment, and (b) by quantifying the number of volunteers with no response to maximal pulp stimulation (80 reading) on 2 or more consecutive tests, termed anesthetic success. Data were analyzed by McNemar, Mann-Whitney, and paired-samples t tests. Anesthetic success was 52.6% for active and 42.1% for control treatment for lateral incisors, 89.5 and 86.8% respectively for premolars, and 50.0 and 42.1% respectively for first molars (P = .344, 1.0, and .508 respectively). There were no significant differences in the number of episodes of negative response to maximum pulp tester stimulation between active and control massage. A total of 131 episodes were recorded after both active and control massage in lateral incisors (McNemar test, P = 1.0), 329 (active) versus 316 (control) episodes in the premolars (McNemar test, P = .344), and 119 (active) versus 109 (control) episodes respectively for first molars (McNemar test, P = .444). Speed of anesthetic onset and discomfort did not differ between treatments. We concluded that soft tissue massage after MINB does not influence anesthetic efficacy.

Perinatal taurine exposure programs patterns of autonomic nerve activity responses to tooth pulp stimulation in adult male rats.

Perinatal taurine excess or deficiency influences adult health and disease, especially relative to the autonomic nervous system. This study tests the hypothesis that perinatal taurine exposure influences adult autonomic nervous system control of arterial pressure in response to acute electrical tooth pulp stimulation. Female Sprague-Dawley rats were fed with normal rat chow with 3% ß-alanine (taurine depletion, TD), 3% taurine (taurine supplementation, TS), or water alone (control, C) from conception to weaning. Their male offspring were fed with normal rat chow and tap water throughout the experiment. At 8-10 weeks of age, blood chemistry, arterial pressure, heart rate, and renal sympathetic nerve activity were measured in anesthetized rats. Age, body weight, mean arterial pressure, heart rate, plasma electrolytes, blood urea nitrogen, plasma creatinine, and plasma cortisol were not significantly different among the three groups. Before tooth pulp stimulation, low- (0.3-0.5 Hz) and high-frequency (0.5-4.0 Hz) power spectral densities of arterial pressure were not significantly different among groups while the power spectral densities of renal sympathetic nerve activity were significantly decreased in TD compared to control rats. Tooth pulp stimulation did not change arterial pressure, heart rate, renal sympathetic nerve, and arterial pressure power spectral densities in the 0.3-4.0 Hz spectrum or renal sympathetic nerve firing rate in any group. In contrast, perinatal taurine imbalance disturbed very-low-frequency power spectral densities of both arterial pressure and renal sympathetic nerve activity (below 0.1 Hz), both before and after the tooth pulp stimulation. The power densities of TS were most sensitive to ganglionic blockade and central adrenergic inhibition, while those of TD were sensitive to both central and peripheral adrenergic inhibition. The present data indicate that perinatal taurine imbalance can lead to aberrant autonomic nervous system responses in adult male rats.

Anesthetic efficacy of a primary articaine infiltration and a repeat articaine infiltration in the incisive/mental nerve region of mandibular premolars: a prospective, randomized, single-blind study.

INTRODUCTION: The authors conducted a prospective, randomized, single-blind study to determine the degree of pulpal anesthesia obtained with a primary infiltration of 1 cartridge of articaine in the incisive/mental nerve region of the mandibular second premolar and to determine the anesthetic efficacy of a repeat articaine infiltration 20 minutes after the primary infiltration. METHODS: One hundred asymptomatic adult subjects randomly received 2 sets of injections consisting of a primary mandibular second premolar infiltration of 1 cartridge of 4% articaine with 1:100,000 epinephrine plus a repeat infiltration 20 minutes later (using the same volume of articaine) or a mock repeat infiltration in 2 separate appointments spaced at least 1 week apart. The authors used an electric pulp tester to test the first molar, premolars, canine, and incisors for anesthesia in 4-minute cycles for 120 minutes. RESULTS: The success rates of the initial infiltrations for the first molar, canine, and incisor teeth ranged from 59% to 19%. The premolar success rates were moderately successful (ie, 80%-87%), but anesthesia declined after 20-25 minutes. The repeat infiltration at 20 minutes significantly increased the success rate (92%-94%) and the duration of pulpal anesthesia for the premolars. CONCLUSIONS: The initial infiltration was not effective in anesthetizing the first molar, canine, or incisor teeth and was only moderately successful in the premolars. Although the repeat infiltration significantly increased the success rate and duration in the premolars, the initial infiltration success rates were not high enough to support the use of this regimen as a combined anesthetic technique.

Involvement of ATP in noxious stimulus-evoked release of glutamate in rat medullary dorsal horn: a microdialysis study.

Our electrophysiological studies have shown that both purinergic and glutamatergic receptors are involved in central sensitization of nociceptive neurons in the medullary dorsal horn (MDH). Here we assessed the effects of intrathecal administration of apyrase (a nucleotide degrading enzyme of endogenous adenosine 5-triphosphate [ATP]), a combination of apyrase and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, an adenosine A1 receptor antagonist), or 2,3-O-2,4,6-trinitrophenyl-adenosine triphosphate (TNP-ATP, a P2X1, P2X3, P2X2/3 receptor antagonist) on the release of glutamate in the rat MDH evoked by application of mustard oil (MO) to the molar tooth pulp. In vivo microdialysis was used to dialyse the MDH every 5 min, and included 3 basal samples, 6 samples after drug treatment and 12 samples following application of MO. Tooth pulp application of MO induced a significant increase in glutamate release in the MDH. Superfusion of apyrase or TNP-ATP alone significantly reduced the MO-induced glutamate release in the MDH, as compared to vehicle. Furthermore, the suppressive effects of apyrase on glutamate release were reduced by combining it with DPCPX. This study demonstrates that application of an inflammatory irritant to the tooth pulp induces glutamate release in the rat MDH in vivo that may be reduced by processes involving endogenous ATP and adenosine.

Pulsed Nd: YAG laser induces pulpal analgesia: a randomized clinical trial.

This double-blind, randomized, clinical trial investigated the effectiveness and underlying mechanism of neural inhibition of pulsed Nd:YAG laser induction of pulpal analgesia compared with 5% EMLA anesthetic cream. Forty-four paired premolars from 44 orthodontic patients requiring bilateral premolar extraction from either dental arch were randomly assigned to the 'Laser plus Sham-EMLA' or 'EMLA plus Sham-Laser' treatment group. Analgesia was tested by an Electric Pulp Tester (EPT) and the cutting of a standardized cavity, which was terminated when participants reported sensitivity, and Visual Analogue Scale (VAS) and numbness were recorded. Statistical analyses were done by paired t test, McNemar's test, and a chi-squared test (p < 0.05). Sixty-eight percent of laser- and 59% of EMLA-treated teeth had completed cavities with statistically significant EPT increases above baseline. No significant within-patient differences were found for either group. No laser-treated participants reported numbness. The trial confirmed that the pulsed Nd:YAG laser effectively induced pulpal analgesia, by suppression of intradental nerve responses to electrical and mechanical stimuli. Such a laser provides an alternative for dental pain management (ANZ-Clinical Trial Registry: N12611001099910).

Periodontal ligament and intraosseous anesthetic injection techniques: alternatives to mandibular nerve blocks.

BACKGROUND: and Overview. The provision of mandibular anesthesia traditionally has relied on nerve block anesthetic techniques such as the Halsted, the Gow-Gates and the Akinosi-Vazirani methods. The authors present two alternative techniques to provide local anesthesia in mandibular teeth: the periodontal ligament (PDL) injection and the intraosseous (IO) injection. The authors also present indications for and complications associated with these techniques. CONCLUSIONS: The PDL injection and the IO injection are effective anesthetic techniques for managing nerve block failures and for providing localized anesthesia in the mandible. CLINICAL IMPLICATIONS: Dentists may find these techniques to be useful alternatives to nerve block anesthesia.

A prospective, randomized single-blind study of the anesthetic efficacy of frequency-dependent conduction blockade of the inferior alveolar nerve.

INTRODUCTION: The purpose of this prospective, randomized single-blind study was to evaluate the degree of pulpal anesthesia obtained with frequency-dependent conduction blockade of the inferior alveolar nerve (IAN). METHODS: Eighty adult volunteers randomly received two IAN blocks: an IAN block followed by continuous electrical stimulation for 3 minutes of the first molar or lateral incisor for six cycles over a time period of 64 minutes; an IAN block followed by mock electrical stimulation using the same cycles. The IAN blocks were administered at two separate appointments spaced at least 1 week apart in a crossover design. An electric pulp tester was used to test for anesthesia of the first molar and lateral incisor. Anesthesia was considered successful when two consecutive 80 readings were obtained within 15 minutes, and the 80 reading was recorded through the 60th minute. RESULTS: The anesthetic success rate for the stimulated IAN block was 35% and 48% for the lateral incisor and first molar, respectively. For the mock stimulated IAN, success was 18% for the lateral incisor and 62% for the first molar. There was no significant difference between the two IAN block techniques. CONCLUSIONS: We concluded that the stimulation of nerves in the presence of local anesthesia (frequency-dependent nerve block) did not statistically increase the success rate of pulpal anesthesia for an IAN block.

The role of N-methyl-D-aspartate receptor subunits in the rat thalamic mediodorsal nucleus during central sensitization.

We have identified tooth pulp-driven neurons (TPDNs) in the thalamic mediodorsal nucleus (MD) in rats and showed that the TPDNs' responsiveness in the MD is increased by chemical conditioning stimulation of allyl-isothiocyanate (mustard oil) to the molar tooth pulp. The aim of the present study was to address the role of N-methyl-d-aspartate receptors (NMDA receptors) in the sensitized central nervous system following the mustard oil application to the rat tooth pulp. Microinjection of MK-801, a noncompetitive NMDA receptor antagonist, to the thalamic MD nucleus reduced the TPDNs' responsiveness in the thalamic MD nucleus. Gene expression analysis showed that expression levels of NMDA receptor subunits NR2A and NR2D mRNAs in the thalamus were increased by the mustard oil application and that the increases were reduced by MK-801. When naloxone, an opioid receptor antagonist, was given systemically following the MK801 microinjection, the TPDNs' responsiveness was rekindled and expression levels of NR2D and NR2A mRNAs were increased. Moreover, lidocaine pretreatment abolished the mustard oil-induced upregulation of NR2D and NR2A mRNAs. These results suggest that, during central sensitization, interaction of NMDA receptors and endogeneous opioid-related inhibitory mechanisms plays critical role in the alteration of the TPDNs' responsiveness in the thalamic MD nucleus.

Mechanisms and treatment approaches of dentine hypersensitivity: a literature review.

PURPOSE: To review major mechanisms of dentine hypersensitivity and the treatment approaches offered. MATERIALS AND METHODS: Medline was used to find relevant literature published up to December 2006. Based on abstracts and full articles, studies (in human and in animals) were identified describing mechanisms and management of dentine hypersensitivity. Additional information was also obtained by using manual library search for relevant topics in standard texts and journals of dentistry. RESULTS: Discussion about the sensitivity of dentine started over a century ago, but it was not until sixty years later that a possible theory was posited. The so-called hydrodynamic theory became popular and was applied to understand the mechanism responsible for hypersensitive dentine. Nevertheless, because of the discrepancies in the pattern by which the dentine responds to various stimuli, several theories of dentine hypersensitivity were proposed which include the hydrodynamic theory, odontoblast transducer mechanism and direct innervation theory. None of these mechanisms was said to fully explain dentine hypersensitivity, thus indicating that as-yet unexplained mechanisms were possibly responsible. A multitude of products were tried and reported to be effective. The efficacy of many was not clearly established and their mechanisms of action were inadequately elucidated. The potential of gene therapy to reduce the burden of dentine hypersensitivity in the future is being examined. CONCLUSIONS: Considerable effort has been made to precisely explain dentine hypersensitivity, but doubt still exists whether any one theory can be applied to understanding this condition. This has led to a constant increase in therapeutic approaches worldwide, but with no conclusive evidence of reliable, successful treatment regimens.

The efficacy of infiltration anaesthesia for adult mandibular incisors: a randomised double-blind cross-over trial comparing articaine and lidocaine buccal and buccal plus lingual infiltrations.

AIM: To compare the efficacy of 2% lidocaine and 4% articaine both with 1:100,000 adrenaline in anaesthetising the pulps of mandibular incisors. METHODS: Thirty-one healthy adult volunteers received the following local anaesthetic regimens adjacent to a mandibular central incisor: 1) buccal infiltration of 1.8 mL lidocaine plus dummy lingual injection (LB), 2) buccal plus lingual infiltrations of 0.9 mL lidocaine (LBL), 3) buccal infiltration of 1.8 mL articaine plus dummy lingual injection (AB), 4) buccal plus lingual infiltrations of 0.9 mL articaine (ABL). Pulp sensitivities of the central incisor and contralateral lateral incisor were assessed electronically. Anaesthetic efficacy was determined by two methods: 1) Recording the number of episodes with no responses to maximal electronic pulp tester stimulation during the course of the study period, 2) recording the number of volunteers with no response to maximal pulp tester stimulation within 15 min and maintained for 45 min (defined as sustained anaesthesia). Data were analysed by McNemar, chi-square, Mann-Whitney and paired t-tests. RESULTS: For both test teeth, the number of episodes of no sensation on maximal stimulation was significantly greater after articaine than lidocaine for both techniques. The split buccal plus lingual dose was more effective than the buccal injection alone for both solutions (p <0.001). 4% articaine was more effective than 2% lidocaine when comparing sustained anaesthesia in both teeth for each technique (p <0.001), however, there was no difference in sustained anaesthesia between techniques for either tooth or solution. CONCLUSIONS: 4% articaine was more effective than 2% lidocaine (both with 1:100,000 adrenaline) in anaesthetising the pulps of lower incisor teeth after buccal or buccal plus lingual infiltrations.

Neuron-immune interactions in the sensitized thalamus induced by mustard oil application to rat molar pulp.

We have reported that mustard oil application to the rat dental pulp induces neuronal activation in the thalamus. To address the mechanisms involved in the thalamic changes, we performed neuronal responsiveness recording, immunohistochemistry, and molecular biological analysis. After mustard oil application, neuronal responsiveness was increased in the mediodorsal nucleus. When MK801 (an N-methyl-D-aspartate receptor antagonist) was applied to the mediodorsal nucleus, the enhanced responsiveness was decreased. N-methyl-D-aspartate receptor 2D, glial fibrillary acidic protein, and antigen-presenting cell-related gene mRNAs in the contralateral thalamus were up-regulated at 10 minutes after mustard oil application, but were down-regulated within 10 minutes after the antagonist application. OX6-expressing microglia and glial fibrillary acidic protein-expressing astrocytes did not increase until 60 minutes after mustard oil application. These results suggested that the thalamic neurons play some roles in regulating the glial cell activation in the mediodorsal nucleus via N-methyl-D-aspartate receptor 2D during pulp inflammation-induced central sensitization.

A prospective, randomized single-blind study of the anesthetic efficacy of the inferior alveolar nerve block administered with a peripheral nerve stimulator.

INTRODUCTION: The purpose of this prospective, randomized single-blind study was to compare the degree of pulpal anesthesia obtained with the inferior alveolar nerve (IAN) block administered by using a peripheral nerve stimulator compared with a conventional IAN block by using a cartridge of 2% lidocaine with 1:100,000 epinephrine. METHODS: Forty-six adult volunteers randomly received a conventional IAN block or an IAN block administered with a peripheral nerve stimulator at 2 separate appointments. An electric pulp tester was used to test for anesthesia of the first molar, first premolar, and lateral incisor in 4-minute cycles for 60 minutes. Anesthesia was considered successful when 2 consecutive 80 readings were obtained within 15 minutes, and the 80 reading was continuously sustained through the 60th minute. RESULTS: With the peripheral nerve stimulator for the IAN block, successful pulpal anesthesia ranged from 32%-37%. For the conventional IAN block, successful pulpal anesthesia ranged from 32%-45%. There was no significant difference between the 2 IAN block techniques. CONCLUSIONS: We concluded that the IAN block administered with a peripheral nerve stimulator did not increase the success rate of pulpal anesthesia when compared with a conventional IAN block.

Glutamine uptake contributes to central sensitization in the medullary dorsal horn.

Mustard oil application to tooth pulp produces central sensitization in rat medullary dorsal horn (MDH) nociceptive neurons, which has been implicated in persistent pain mechanisms. We found that superfusion onto MDH of methylaminoisobutyric acid, a competitive inhibitor of the neuronal system A transporter for presynaptic uptake of glutamine (a glutamate precursor released from astroglia), significantly depressed development of mustard oil-induced central sensitization in rat MDH nociceptive neurons. This finding indicates that the system A transporter is required for the expression of central sensitization and confirms the important roles of astroglia, glutamine and presynaptic modulation of glutamate release in the development of central sensitization.

Electric pulp testing: a review.

Electric pulp testing (EPT) has been available for more than a century and used in dental practices worldwide. This article provides an overview of this diagnostic aid. The PubMed database from 1953 was used initially; the reference list for pulp testing featured 1071 articles, and for EPT identified 121 papers. A forward search was undertaken on these articles and using selected author names. Potentially relevant material was also sought in contemporary endodontic texts, while older textbooks on endodontics, operative dentistry and pain revealed historic information and primary research not found electronically. A short account of the innervation of the pulp is followed by an historic overview. Clinical considerations discussed include tooth isolation, glove wearing and tester electrode placement. Orthodontic treatment, pacemaker wearing and patient medications are considered. Research applications are also discussed. While EPT is valuable, no single pulp testing technique can reliably diagnose all pulp conditions. Careful collection of patient history regarding the problem tooth and prudent use of appropriate radiographs are also helpful. The shortcomings of electric tests, especially in the case of immature and concussed teeth, must be understood. The demeanour of the patient and the responses given by control teeth also require careful consideration.

The effects of ibuprofen and the neurokinin-1 receptor antagonist GR205171A on Fos expression in the ferret trigeminal nucleus following tooth pulp stimulation.

We have developed a model to study central changes following inflammation of the tooth pulp in the ferret and have examined Fos expression in the trigeminal nucleus following stimulation of non-inflamed and inflamed tooth pulps. The aim of this study was to establish the ability of this model to predict analgesic efficacy in clinical studies of inflammatory pain. We addressed this by assessing the effects of the neurokinin-1 receptor antagonist GR205171A and ibuprofen on Fos expression following stimulation of the inflamed pulp and comparing this with known analgesic efficacy. Adult ferrets were prepared under anaesthesia to allow tooth pulp stimulation, recording from the digastric muscle and intravenous injections at a subsequent experiment. In some animals pulpal inflammation was induced, by introducing human caries into a deep buccal cavity. After 5 days, animals were reanaesthetised, treated with vehicle, GR205171A or ibuprofen and the teeth were stimulated at ten times the threshold of the jaw-opening reflex. Stimulation of all tooth pulps induced ipsilateral Fos in trigeminal subnuclei caudalis and oralis. GR205171A had no significant effect on Fos expression in the trigeminal nucleus of animals with either non-inflamed or inflamed tooth pulps. Ibuprofen reduced Fos expression in the trigeminal nucleus and this effect was most marked in animals with pulpal inflammation. These results differ from those previously described using a range of other animal models, but agree with known clinical efficacy of neurokinin-1 receptor antagonists and ibuprofen. Therefore this model is likely to be of use in accurately predicting the analgesic efficacy of novel compounds.

Central sensitization induced in thalamic nociceptive neurons by tooth pulp stimulation is dependent on the functional integrity of trigeminal brainstem subnucleus caudalis but not subnucleus oralis.

We have previously demonstrated that application of the inflammatory irritant mustard oil (MO) to the rat molar tooth pulp induces central sensitization in nociceptive neurons within the contralateral ventroposterior medial (VPM) nucleus and posterior nuclear group (PO) of the thalamus as well as brainstem subnucleus caudalis (Vc) and subnucleus oralis (Vo). Since Vc and Vo are important relays of pulp afferent input to thalamus, the aim of this study was to test if local application of the synaptic blocker CoCl2 to Vc or Vo influences the pulp-induced thalamic central sensitization. The activity of 32 nociceptive-specific (NS) neurons within the rat VPM and immediately adjacent PO was recorded. Spontaneous activity, mechanoreceptive field (RF), mechanical activation threshold and evoked responses to graded mechanical stimuli were assessed before and after MO application to the pulp. MO application evoked immediate but short-lasting neuronal discharges in 21 of the 32 NS neurons tested, as well as central sensitization reflected in significant and long-lasting (> 60 min) RF expansion, decrease in activation threshold, and increase in graded pinch-evoked responses in all 32 NS neurons. CoCl2 applied to the ipsilateral Vc significantly attenuated these pulp-induced changes for 20 min or more. In contrast, CoCl2 applied to the ipsilateral Vo did not reverse this MO-induced central sensitization. Isotonic saline applied to Vc or Vo was also ineffective. These findings indicate that central sensitization induced in nociceptive neurons within VPM and PO by noxious stimulation of the tooth pulp is dependent upon the functional integrity of Vc but not Vo.

Central sensitization in thalamic nociceptive neurons induced by mustard oil application to rat molar tooth pulp.

We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.