Tooth Pulp Stimulation Research Articles

Release of Endocannabinoids into the Cerebrospinal Fluid during the Induction of the Trigemino-Hypoglossal Reflex in Rats.

The endocannabinoid system (ECS) plays an important role in pain processing and modulation. Since the specific effects of endocannabinoids within the orofacial area are largely unknown, we aimed to determine whether an increase in the endocannabinoid concentration in the cerebrospinal fluid (CSF) caused by the peripheral administration of the FAAH inhibitor URB597 and tooth pulp stimulation would affect the transmission of impulses between the sensory and motor centers localized in the vicinity of the third and fourth cerebral ventricles. The study objectives were evaluated on rats using a method that allowed the recording of the amplitude of evoked tongue jerks (ETJ) in response to noxious tooth pulp stimulation and URB597 treatment. The amplitude of ETJ was a measure of the effect of endocannabinoids on the neural structures. The concentrations of the endocannabinoids tested (AEA and 2-AG) were determined in the CSF, along with the expression of the cannabinoid receptors (CB1 and CB2) in the tissues of the mesencephalon, thalamus, and hypothalamus. We demonstrated that anandamide (AEA), but not 2-arachidonoylglycerol (2-AG), was significantly increased in the CSF after treatment with a FAAH inhibitor, while tooth pulp stimulation had no effect on the AEA and 2-AG concentrations in the CSF. We also found positive correlations between the CSF AEA concentration and cannabinoid receptor type 1 (CB1R) expression in the brain, and between 2-AG and cannabinoid receptor type 2 (CB2R), and negative correlations between the CSF concentration of AEA and brain CB2R expression, and between 2-AG and CB1R. Our study shows that endogenous AEA, which diffuses through the cerebroventricular ependyma into CSF and exerts a modulatory effect mediated by CB1Rs, alters the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve. In addition, our findings may be consistent with the emerging concept that AEA and 2-AG have different regulatory mechanisms because they are involved differently in orofacial pain. We also suggest that FAAH inhibition may offer a therapeutic approach to the treatment of orofacial pain.

Effect of Fatty Acid Amide Hydrolase Inhibitor URB597 on Orofacial Pain Perception in Rats.

Endocannabinoids act as analgesic agents in a number of headache models. However, their effectiveness varies with the route of administration and the type of pain. In this study, we assessed the role of the fatty acid amide hydrolase inhibitor URB597 in an animal model of orofacial pain based on tooth pulp stimulation. More specifically, we assessed the effects of intracerbroventricular (i.c.v.) and intraperitoneal (i.p.) administration of URB597 on the amplitude of evoked tongue jerks (ETJ) in rats. The levels of the investigated mediators anandamide (AEA), 2-arachidonyl glycerol (2-AG), Substance P (SP), calcitonin-gene-related peptide (CGRP), endomorphin-2 (EM-2) and fatty acid amide hydrolase (FAAH) inhibitor by URB597 and receptors cannabinoid type-1 receptors (CB1R), cannabinoid type-2 receptors (CB2R) and µ-opioid receptors (MOR) were determined in the mesencephalon, thalamus and hypothalamus tissues. We have shown that increasing endocannabinoid AEA levels by both central and peripheral inhibition of FAAH inhibitor by URB597 has an antinociceptive effect on the trigemino-hypoglossal reflex mediated by CB1R and influences the activation of the brain areas studied. On the other hand, URB597 had no effect on the concentration of 2-AG in the examined brain structures and caused a significant decrease in CB2R mRNA expression in the hypothalamus only. Tooth pulp stimulation caused in a significant increase in SP, CGRP and EM-2 gene expression in the midbrain, thalamus and hypothalamus. In contrast, URB597 administered peripherally one hour before stimulation decreased the mRNA level of these endogenous neuropeptides in comparison with the control and stimulation in all examined brain structures. Our results show that centrally and peripherally administered URB597 is effective at preventing orofacial pain by inhibiting AEA catabolism and reducing the level of CGRP, SP and EM-2 gene expression and that AEA and 2-AG have different species and model-specific regulatory mechanisms. The data presented in this study may represent a new promising therapeutic target in the treatment of orofacial pain.

Age Differences in Naloxone Reversibility of Electroacupuncture on the Jaw Opening Reflex in Rats.

Electroacupuncture is one of the most popular physical treatments for clinical pain, but the potential influence of a patient's age on the effectiveness of electroacupuncture treatment has not been clearly established. Objectives: The present study aimed to detect a potential difference in electroacupuncture- induced analgesia between juvenile and adult rats. In this study, we investigated the effects of electroacupuncture treatment on the nociceptive jaw-opening reflex evoked by tooth-pulp stimulation in juvenile and adult rats. Our results showed there were age differences in electroacupuncture-induced analgesic effects in rats, especially with naloxone antagonization. The ratio of naloxonereversibility against electroacupuncture analgesia was greater in adult rats than in juvenile rats. These results suggest that electroacupuncture analgesia is produced mainly by the non-opioid system in juvenile rats and by the opioid system in adult rats.

Opioid and Endocannabinoid System in Orofacial Pain

Orofacial pain disorders are frequent in the general population and their pharmacological treatment is difficult and controversial. Therefore, the search for novel, safe and efficient analgesics is an important but still elusive goal for contemporary medicine. In the recent years, the antinociceptive potential of endocannabinoids and opioids has been emphasized. However, concerns for the safety of their use limit their clinical applications. the possibility of modulating the activity of endocannabinoids by regulation of their synthesis and/or degradation offers an innovative approach to the treatment of pain. A rat model of trigeminal pain, utilizing tongue jerks evoked by electrical tooth pulp stimulation during perfusion of the cerebral ventricles with various neurotransmitter solutions can be used in the pharmacological studies of nociception in the orofacial area. The aim of this review is to present the effects of pharmacological activity of opioids and endocannabinoids affecting the transmission of the sensory information from the orofacial area on the example of trigemino-hypoglossal reflex in rats.

Effect of conditioning stimulation of the fornix on the response of thalamic nociceptive neurons to tooth pulp stimulation

Effect of conditioning stimulation of the fornix on the response of thalamic nociceptive neurons to tooth pulp stimulation

Differential effects of systemic morphine on responses elicited by tooth pulp stimulation of nociceptive neurons in lateral and medial thalamic nuclei.

The effects of intravenous morphine on responses of feline thalamic nociceptive neurons receiving afferent input from the tooth pulp (TP) were investigated. Morphine suppressed responses to TP stimulation in both tooth pulp specific (TPS) and wide dynamic range (WDR) neurons with TP input recorded from the nucleus ventralis posteromedialis (VPM). However, there was scant morphine effect on responses to stimulation of trigeminothalamic tract (TTT) fibers in the trigeminal medial lemniscus. Furthermore, in nociceptive neurons with TP input recorded from nucleus centralis lateralis (CL) and parafascicularis (Pf) of the intralaminar nuclei, intravenous morphine suppressed responses both to stimulation of the mesencephalic reticular formation (MRF) as well as TP stimulation. The suppressive action of morphine on responses elicited by TP stimulation of VPM, CL and Pf neurons was antagonized by intravenous naloxone (1 mg/kg). Results suggest that intravenous morphine suppresses synaptic transmission of nociceptive impulses in the intralaminar nuclei as well as in the lower brain stem but not in the VPM.

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.

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.

Noxious Stimulation of the Rat Tooth Pulp May Impair Learning and Memory Through the Induction of Hippocampal Apoptosis.

To determine whether noxious stimulation of the rat tooth pulp induces learning and memory impairment through the induction of apoptosis in the hippocampus. Thirty-five adult rats were divided randomly into five groups (each n=7) as follows: control, sham-operated, sham-vehicle, capsaicin-treated, and capsaicin plus ibuprofen-treated group. After preparing dental cavities via cutting 2 mm of the distal extremities of the mandibular incisors, polyethylene crowns were placed on the teeth. Based on the study groups, different injections were administered into the cavities. Nociceptive scores for each block were obtained by measuring the number of seconds that the animal spent rubbing and flicking the lower jaw. After recording the nociceptive behaviors, spatial learning and memory were assessed by using the Morris Water Maze (MWM) test. The hippocampal levels of Bcl-2, Bax, and caspase-3 protein were determined by immunoblotting. Statistical analyses were performed using one- or two-way analysis of variance. Noxious pulp stimulation induced by intradental application of capsaicin significantly increased time and traveled distance in the MWM test. Capsaicin stimulation of the pulp also significantly increased the Bax:Bcl-2 ratio and activated caspase-3 in the hippocampus (P<.01), which was inhibited by ibuprofen pretreatment (P<.05). Memory and learning impairment induced by noxious stimulation of the rat tooth pulp may be correlated with activation of apoptotic pathways in the hippocampus.

Trigemino-hypoglossal somatic reflex in the pharmacological studies of nociception in orofacial area

Disorders involving the orofacial area represent a major medical and social problem. They are a consequence of central nociceptive processes associated with stimulation of the trigeminal nerve nucleus. A rat model of trigeminal pain, utilizing tongue jerks evoked by electrical tooth pulp stimulation during perfusion of the cerebral ventricles with various neuropeptide solutions, can be used in the pharmacological studies of nociception in orofacial area. The investigated neuropeptides diffuse through the cerebroventricular lining producing an analgesic effect either directly, through the trigemino-hypoglossal reflex arc neurons or indirectly through the periaqueductal central gray, raphe nuclei or locus coeruleus neurons. The aim of this review is to present the effect of pharmacological activity of various neuropeptides affecting the transmission of the sensory information from the orofacial area on the example of trigemino-hypoglossal reflex in rats.

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.

Effects of repeated tooth pulp stimulation on concentrations of plasma catecholamines, corticosterone, and glucose in rats

In this study, we examined whether tooth pulp stimulation (TPS) affects the stress responses in anesthetized rats. As for stress response indices, we monitored changes in the concentrations of plasma catecholamines (CAs) (adrenaline, noradrenaline, and dopamine), corticosterone (CS), and glucose (Glu). We observed that repeated TPS attenuated plasma adrenaline, dopamine, CS, and Glu levels compared with those of sham-TPS. After administering naloxone, an opioid antagonist, repeated TPS reversed the decreases in plasma CAs, CS, and Glu. These findings showed that the effects of repeated TPS may be mediated by endogenous opioid administration. Our findings suggest that repeated TPS can induce stress-analgesia and that an endogenous descending pain modulation system exists.

Pain Fiber Anesthetic Reduces Brainstem Fos after Tooth Extraction

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.

Selective stimulation of human tooth-pulp with a new stable method: Responses and validation

The aims of this study were to establish a safe technique for selective stimulation of nerves in human tooth-pulp during long experiments and to validate its use even with stimuli of high intensities. A custom-made veneer containing 2 silver wire-conductive cream electrodes was attached with cement to the labial surface of an upper central incisor tooth. A variety of stimulus intensities were applied, and sensory and reflex responses from jaw-closing muscles were recorded. In 15 participants, the stimuli evoked predominantly sharp or painful sensations and reflex inhibitions of activity in the jaw muscles. Stimulation of 3 non-vital teeth evoked no sensations or reflexes, even at intensities that evoked maximal reflexes in vital teeth. The electrodes had reasonably stable resistances throughout experiments lasting up to 90 min. The method described enables responses to low- or high-intensity stimulation of human pulpal nerves to be investigated in long experiments.

Systemic pregabalin attenuates facial hypersensitivity and noxious stimulus-evoked release of glutamate in medullary dorsal horn in a rodent model of trigeminal neuropathic pain

Pregabalin is effective in treating many neuropathic pain conditions. However, the mechanisms of its analgesic effects remain poorly understood. The aim of the present study was to determine whether pregabalin suppresses facial mechanical hypersensitivity and evoked glutamate release in the medullary dorsal horn (MDH) in a rodent model of trigeminal neuropathic pain. Nociceptive mechanical sensitivity was assessed pre-operatively, and then post-operatively 1h following pregabalin or vehicle (saline) treatment on post-operative days 2 and 5 following infraorbital nerve transection (IONX). In addition, an in vivo microdialysis probe was inserted into the exposed medulla post-operatively and dialysate samples were collected. Glutamate release was then evoked by mustard oil (MO) application to the tooth pulp, and the effects of pregabalin or vehicle were examined on the MDH glutamate release. Glutamate concentrations in the dialysated samples were determined by HPLC, and data analyzed by ANOVA. IONX animals (but not control animals) showed facial mechanical hypersensitivity for several days post-operatively. In addition, tooth pulp stimulation with MO evoked a transient release of glutamate in the MDH of IONX animals. Compared to vehicle, administration of pregabalin significantly attenuated the facial mechanical hypersensitivity as well as the MO-evoked glutamate release in MDH. This study provides evidence in support of recent findings pointing to the usefulness of pregabalin in the treatment of orofacial neuropathic pain.

Evidence for anti-inflammatory and putative analgesic effects of a monoclonal antibody to calcitonin gene-related peptide

BackgroundCalcitonin gene-related peptide (CGRP) is a powerful pro-inflammatory mediator thought to play a significant role in the development of inflammation and pain. We investigated the role of CGRP in trigeminal inflammatory pain by determining the ability of a monoclonal antibody to CGRP to modify central Fos expression in response to stimulation of the inflamed ferret tooth pulp. We also assessed the effect of the antibody on pulpal inflammation. MethodsTen adult ferrets were prepared under anaesthesia to allow stimulation of the upper and lower left canine pulps, recording from the digastric muscle and intravenous injections at subsequent experiments. In all animals, pulpal inflammation was induced by introducing human caries into a deep buccal cavity. Four days later animals were treated intravenously with either CGRP antibody (n=5) or vehicle (n=5). After a further 2days animals were re-anaesthetised and the tooth pulps stimulated at 10times jaw-opening reflex threshold. Brainstems and tooth pulps were processed immunohistochemically for Fos and the common leucocyte marker CD45, respectively. ResultsFos was expressed in ipsilateral trigeminal subnuclei caudalis (Vc) and oralis (Vo). Significantly fewer Fos-positive nuclei were present within Vc of CGRP antibody-treated animals (p=0.003 vs vehicle-treated). Mean percentage area of staining for CD45 was significantly less in antibody-treated animals (p=0.04 vs vehicle-treated). ConclusionsThis is the first direct evidence that sequestration of CGRP has anti-inflammatory and putative analgesic effects. Previous studies using this Fos model have demonstrated that it is able to predict clinical analgesic efficacy. Thus these data indicate that this antibody may have analgesic effects in dental pain and other types of inflammatory-mediated transmission, and suggest that this is in part due to peripheral anti-inflammatory effects.

The striatum and pain modulation.

The aim of this review was to give a general aspect of the sensorial function of the striatum related to pain modulation, which was intensively studied in our laboratory. We analyse the effect of electrical and chemical stimulation of the striatum on the orofacial pain, especially that produced by tooth pulp stimulation of the lower incisors. We demonstrated specific sites within the nucleus which electrical or chemical stimulation produced inhibition of the nociceptive jaw opening reflex. This analgesic action of the striatum was mediated by activation of its dopamine D(2) receptors and transmitted through the indirect pathways of the basal ganglia and the medullary dorsal reticular nucleus (RVM) to the sensorial nuclei of the trigeminal nerve. Its mechanism of action was by inhibition of the nociceptive response of the second order neurons of the nucleus caudalis of the V par.

Effect of tooth pulp and periaqueductal central gray electrical stimulation on β-endorphin release into the fluid perfusing the cerebral ventricles in rats

Our previous studies demonstrated that tooth pulp stimulation increases the pain threshold, whereas stimulation of the periaqueductal central gray (PAG) has the opposite effect. The aim of this study was to investigate the effect exerted by electrical stimulation of the nociceptive afferent terminals in the tooth pulp and analgesic electrical stimulation of the PAG on the release of immunoreactive β-endorphin (β-EP-IR) into the cerebrospinal fluid (CSF) and artificial cerebrospinal fluid (aCSF) perfusing the cerebral ventricles in rat, and to establish whether during such stimulation the μ-opioid receptor (MOR) was activated. The tongue jerk reflex was induced by dental pulp stimulation in rats under chloralose anesthesia. CSF was collected from the cerebello-medullary cistern, and then 30-minute perfusions of the lateral ventricles with aCSF were conducted with collection of perfusate portions from the cerebello-medullary cistern at rest (control), during electrical tooth pulp stimulation evoking the nociceptive tongue jerk reflex and during inhibition of that reflex with simultaneous stimulation of tooth pulp and the PAG. In the second series of experiments, a MOR-selective antagonist, β-funaltrexamine (β-FNA) was perfused through the cerebral ventricles 10min before tooth pulp stimulation. β-EP-IR was determined in the collected CSF and aCSF perfusates by radioimmunoassay (RIA). Stimulation of tooth pulp with electrical impulses resulted in a significant increase of β-EP-IR. On the other hand, simultaneous tooth pulp and PAG stimulation inhibited β-EP-IR release into the fluid perfusing the cerebral ventricles. β-FNA blocked evoked tongue jerks (ETJ) induced by PAG stimulation, but no enhancing effect of β-FNA on β-EP-IR release into the perfusate was observed. The obtained results indicate that stimulation of the tooth pulp increases β-EP release significantly, whereas PAG stimulation significantly inhibits β-EP-IR release into the CSF, and that these effects are mediated by MOR. The results of the experiments allow to conclude that endogenous β-EP, released as a result of electrical tooth pulp stimulation in orofacial pain, diffuses through the cerebroventricular ependyma into the CSF and exerts a modulatory effect, mediated by MOR, alterating the properties of neurons in the trigeminal sensory nuclei, interneurons, and motoneurons of the hypoglossal nerve.

Effect of tooth pulp and periaqueductal central gray stimulation on the expression of genes encoding the selected neuropeptides and opioid receptors in the mesencephalon, hypothalamus and thalamus in rats

Nociceptive stimulation has been considered to affect the expression of genes encoding endogenous neuropeptides and their receptors. The effect of electric stimulation of the tooth pulp and/or periaqueductal gray (PAG) in rats on mRNA levels of the selected neuropeptides and opioid receptors (ORs) was investigated in comparison with control group, without stimulation. The levels of mRNA for the selected neuropeptides: galanin (GAL), vasopressin (AVP), oxytocin (OT), substance P (SP), somatostatin (SOM), vasoactive intestinal peptide (VIP), endomorphin-2 (EM-2), and opioid receptors: MOR, DOR and KOR in mesencephalic, hypothalamic and thalamic tissues were determined by real-time PCR. It was demonstrated that in the control group expression of the tested neuropeptides was at a very low level in the mesencephalon and thalamus, but at the higher level in the hypothalamus. The highest expression of ORs was observed in the mesencephalon. Nociceptive tooth pulp stimulation had the strongest effect in the hypothalamus, elevating mRNA levels of all tested neuropeptides except SOM. Electric stimulation of PAG either did not change or down-regulated mRNA levels of the neuropeptides in the cerebral structures. Simultaneous stimulation of PAG and tooth pulp either did not affect mRNA levels of the investigated neuropeptides or caused their slight decrease versus tooth pulp stimulation. The noxious stimulation of tooth pulp increased also the levels of OR mRNAs, while stimulation of PAG had the opposite effect. The above results demonstrated that tooth pulp stimulation significantly up-regulated the mRNA levels for a number of neuropeptides and all three types of ORs in the rat brain, which would result in more potent antinociception. In contrast, PAG stimulation down-regulated the mRNA levels of several neuropeptides and ORs in the cerebral tissues, which would cause decreased synthesis of ORs. The obtained results represent a new insight into the mechanism of orofacial pain.

Etodolac Attenuates Hippocampal Blood Flow Responses Induced by Tooth Pulp Stimulation in Rats

In this study, we investigated whether increases in hippocampal blood flow (HBF) by tooth pulp stimulation (TPS) are mediated via the activation of cyclooxygenase-2 (COX-2). We measured mean arterial blood pressure (MABP) and HBF in urethane-anesthetized rats using laser Doppler flowmetry and examined the effects of etodolac, a specific COX-2 inhibitor, on TPS-induced MABP and HBF responses. The MABP response was not attenuated by the intraperitoneal (i.p.) administration of etodolac (10 mg/kg); however, the HBF response was significantly attenuated by etodolac administration. These results suggest that COX-2 may be involved in the mechanisms regulating TPS-induced HBF responses.

Cortical stimulation and tooth pulp evoked potentials in rats: a model of direct anti-nociception.

While the effect of cortex stimulation on pain control is widely accepted, its physiological basis remains poorly understood. We chose an animal model of pain to study the influence of sensorimotor cortex stimulation on tooth pulp stimulation evoked potentials (TPEPs). Fifteen awake rats implanted with tooth pulp, cerebral cortex, and digastric muscle electrodes were divided into three groups, receiving 60 Hz, 40 Hz and no cortical stimulation, respectively. TPEPs were recorded before, one, three and five hours after continuous stimulation. We observed an inverse relationship between TPEP amplitude and latency with increasing tooth pulp stimulation. The amplitudes of the early components of TPEPs increased and their latency decreased with increasing tooth pulp stimulation intensity. Cortical stimulation decreased the amplitude of TPEPs; however, neither the latencies of TPEPs nor the jaw-opening reflex were changed after cortical stimulation. The decrease in amplitude of TPEPs after cortical stimulation may reflect its anti-nociceptive effect.