Electrical Stimulation Of Tooth Pulp Research Articles

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.

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.

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.

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.

Effects of Acupuncture at Large Intestine 4 (LI 4) on Electrical Tooth Pulp Stimulation: A Randomized Controlled Pilot Study

Background: Research studies have shown acupuncture to have efficacy in the treatment of dental pain, as confirmed by the 1997 NIH Consensus Conference on Acupuncture. Objective: To determine if dry needling acupuncture at Hegu Large Intestine 4 acupoint (LI 4) can reduce the dental pulp sensory threshold produced by electrical pulp stimulation of incisor teeth. Design and Setting: A prospective, randomized placebo-controlled, single-blinded pilot study at the Universidad Mayor (university dental clinic), Santiago, Chile. Participants: A total of 40 healthy adults who had never received acupuncture, who were not receiving anticoagulant medication, nor had any incisor dental restorations. Intervention: Manual stimulation of LI 4 or sham acupuncture with a blunt needle that only touched the skin without penetrating it. Main Outcome Measures: Dental pulp sensory threshold evoked by pulp stimulation. Results: No significant differences in pain reduction were found between the volunteers who received real acupuncture and those who received the placebo intervention. Conclusion: Acupuncture performed at LI 4 did not reduce dental pulp sensory threshold.

Systemic administration of lidocaine suppresses the excitability of rat cervical dorsal horn neurons and tooth-pulp-evoked jaw-opening reflex

Although systemic lidocaine has been demonstrated to have analgesic actions in neuropathic pain conditions, the effect of intravenous lidocaine on trigeminal pain has not been elucidated. The aim of the present study is to investigate the effect of intravenous lidocaine administration on the excitability of the upper cervical dorsal horn (C1) neuron having convergent inputs from both tooth-pulp (TP) and facial skin as well as nociceptive jaw-opening reflex (JOR). After electrical stimulation of TP, extracellular single-unit recordings from 19 C1 neurons and the digastric muscle electromyogram (dEMG) were made in pentobarbital-anesthetized rats. These neurons also responded to non-noxious and noxious mechanical stimulation (touch and pinch) of facial skin, and every neuron was considered to be a wide dynamic range (WDR) neuron. The TP-evoked C1 neuronal and dEMG activities were dose-dependently inhibited by systematic administration of lidocaine (1–2 mg/kg, i.v.). After intravenous injection of lidocaine, the unit discharges induced by both touch and pinch stimuli were inhibited, and the size of the receptive field for pinch was also significantly decreased. The mean spontaneous discharge frequencies were significantly inhibited by the application of lidocaine. These changes were reversed within −20 min. These results suggest that in the absence of neuropathic pain intravenous lidocaine injection suppresses the trigeminal nociceptive reflex as well as the excitability of C1 neurons having convergent inputs from TP and somatic afferents. Systemic lidocaine administration, therefore, may contribute to the alleviation of trigeminal-referred pain associated with tooth pain.

Activation of α2-adrenoreceptors suppresses the excitability of C1 spinal neurons having convergent inputs from tooth pulp and superior sagittal sinus in rats

The aim of the present study was to test the hypothesis that activation of alpha(2)-adrenoreceptors modulates the excitability of C1 neurons having convergent inputs from both the tooth pulp (TP) and the superior sagittal sinus (SSS), by using the microiontophoretic techniques of drug application and immunohistochemical approaches. Extracellular single-unit recordings were made from 38 C1 neurons responding to electrical stimulation of TP under pentobarbital-anesthetized rats. Seventy-one percent of C1 neurons (27/38) that responded to TP stimulation also responded to electrical stimulation of the SSS. In these neurons, L: -glutamate-evoked C1 neuronal discharge firings were increased in a dose-dependent manner. The mean glutamate-evoked firing rates were dose-dependently inhibited after microiontophoretic application of clonidine (alpha(2)-adrenoreceptor/imidazoline I(1) receptor agonist). The inhibition of glutamate-evoked C1 mean firings by clonidine was antagonized by the co-application of idazoxan (alpha(2)-adrenoreceptor/imidazoline I(2) receptor antagonist), yohimbine (alpha(2)-adrenoreceptor) but not the alpha(1)-adrenoreceptor antagonist, prazosin with affinity for alpha(2B)- and alpha(2C)-adrenoreceptors. The mean spontaneous discharge frequencies were significantly inhibited by the microiontophoretic application of clonidine and this inhibition was reversed by the co-application of idazoxan, yohimbine. Microiontophoresis of clonidine also resulted in a reduction of TP-/SSS-evoked activity and this effect was reversed by the co-application of yohimbine. Immunoreactivity for alpha(2A)-adrenoreceptor was found in the superficial layers of I-III in the C1 region. These results suggest that alpha(2)-adrenoreceptor agonist clonidine inhibits the excitability of C1 neurons having convergent inputs from TP and SSS afferents, and that the activation of alpha(2A)-adrenoreceptors onto C1 dorsal horn neurons may contribute as a useful therapeutic target for the alleviation of trigeminal referred pain associated with migraine and tooth pain.

Trigeminal pain mechanisms: Effects of ibuprofen and the neurokinin-1 receptor antagonist GR205171A on Fos expression in the ferret trigeminal nucleus following tooth pulp stimulation

We have previously investigated Fos expression after stimulation of normal and inflamed ferret tooth pulps. The aim of this study was to compare the effects of ibuprofen (Sigma, UK) and a neurokinin-1 receptor antagonist GR205171A (GlaxoSmithKline, UK) on the excitability of central trigeminal neurones in response to stimulation of normal and inflamed ferret tooth pulp. Nineteen adult ferrets were prepared under anaesthesia (ketamine 25 mg/kg, xylazine 2 mg/kg: i.m.) to allow tooth pulp stimulation, recording from the digastric muscle and i.v. injections at a subsequent experiment. In ten animals pulpal inflammation was induced, by introducing human caries into a deep cavity. Five days later animals were re-anaesthetised (alphaxalone/alphadalone, induction: 6 mg/kg, maintenance: 6-8 mg/kg/h i.v.) and animals were treated with either ibuprofen (111 mg/kg i.v.; normal n = 4 inflamed n = 5) or GR205171A (500 mg/kg i.v.; normal n = 5, inflamed n = 5). The teeth were stimulated at 10 times the threshold of the jaw-opening reflex for 90 minutes. At 120 minutes from the start of the experiment all animals were perfused with fixative and brainstems processed for Fos immunohistochemistry. Stimulation of normal and inflamed tooth pulps induces ipsilateral Fos expression caudally in subnucleus caudalis (Vc) and rostrally in subnucleus oralis (Vo). GR205171A had no effect on Fos expression in Vc (P > 0.05, unpaired t-test) or Vo (P > 0.05) in either normal or inflamed animals. Ibuprofen reduced Fos expression in Vc (P < 0.05), yet had no effect in Vo (P > 0.05) in both normal and inflamed animals. These results suggest that ibuprofen reduces the number of trigeminal brainstem neurones activated by electrical tooth pulp stimulation caudally but not rostrally in all animals. GR205171A does not modify Fos expression in response to tooth pulp stimulation. Supported by GlaxoSmithKline, UK.

Eye movement-related modulation of trigeminal neuron activity during active sleep and wakefulness

The amplitude of electrically-evoked mass action potentials recorded in the spinal cord and brainstem has been reported to decrease only during eye movement events of active sleep. In contrast, we have reported that the response of trigeminal sensory neurons to peripheral stimuli is modulated throughout the behavioral state of active sleep. It is unclear whether eye movement events contribute to the modulation of trigeminal sensory neuron activity during active sleep. In the present study, eye movement events were demarcated in order to investigate how these events affect peripheral input to trigeminal sensory neurons in chronic, intact, behaving cats. When compared with wakefulness, the mean response of 45 trigeminal sensory neurons to low-intensity electrical stimulation of the canine tooth pulp was significantly suppressed by 28% during periods of active sleep where no eye movement activity was present and by 41% during periods of active sleep with eye movement events. Hence, during active sleep, tooth pulp-evoked responses were significantly decreased by 16% during eye movement events when compared with non-eye movement active sleep. To investigate whether presynaptic inhibition played a role in this phenomenon, the excitability of eight individual tooth pulp afferent terminals during eye movement periods was compared with non-eye movement periods of active sleep. No evidence of eye movement-related depolarization of tooth pulp terminals was detected. When compared to wakefulness, the responses of six trigeminal sensory neurons to air puff stimulation of facial hair mechanoreceptors were significantly increased by 96% during periods of active sleep where no eye movement activity was present but were significantly decreased by 15% during eye movement events when compared with non-eye movement active sleep. The results of the present study indicate that neuronal responses to both tooth pulp and facial hair mechanoreceptor stimulation are significantly attenuated during eye movement events of active sleep.

Pain threshold changes following acupuncture, measured with cutaneous argon laser and electrical tooth pulp stimulation, a comparative study

1. 1. The present study compared the argon laser technique for pain threshold measurements with the previously often used threshold measurements with electrical tooth pulp (TP) stimulation. 2. 2. Conditioning stimuli with acupuncture was given since it previously has been shown to induce pain threshold changes. Acupuncture needles were inserted in the hands and arms and electrically stimulated. 3. 3. The experiments were performed in a single blind fashion comparing pain threshold effects after either acupuncture or placebo. Pain threshold measurements with a method of limits were used with both electrical TP and the argon laser method. 4. 4. In comparison to placebo the pain thresholds increased after acupuncture, both on the face and on the hand, with the argon laser method, while the TP thresholds were not influenced. No significant pain threshold change was detected with either the argon laser or the TP method following placebo treatment. 5. 5. The results indicate that the argon laser used for sensory testing with a method of limits is a useful method for pain threshold measurements. The difference in pain threshold effects induced by acupuncture measured with the argon laser and the TP stimulation, are discussed and related to mechanisms that may differ between the two types of pain threshold measurements.

Pharmacological regulation of descending cortical control of the nociceptive processing

Clinical and experimental data indicate that the cerebral cortex plays an important role in pain perception and endogenous antinociceptive system function. Moreover, the enhancement of descending inhibitory cortical control may be involved in the mechanisms of analgetic effect of some agents. The present study was designed to investigate the effect of cortical electrical stimulation (as a model of descending inhibitory control) on the behavioral and electrophysiological signs of nociceptive response, decipher the mechanisms involved therein and evaluate the action of central analgesics (both opioid and non-opioid) on descending cortical control. In acute experiments in cats the inhibitory cortical influence on neuronal activity produced by nociceptive stimuli (electrical stimulation of tooth pulp, C-fibers of afferent somatic nerves, afferent cardiac structures) was most marked after stimulation of the first and second sensory and fronto-orbital areas. In chronic experiments on rats cortical stimulation reduced behavioral signs of visceral pain (writhing test) and also delayed the development of neuropathic pain syndrome along with lowering its intensity. μ-Opioid receptor agonists (morphine, fentanyl) potentiated the inhibitory cortical effect on the evoked neuronal activity. Pentazocine, which has pronounced κ-receptor agonistic activity, was less effective. Naloxone eliminated the effects of both cortical stimulation and opioid analgesics. Serotonin receptor antagonist methysergide as well as p-chlorophenylalanine significantly decreased inhibitory cortical control and opioids effect. Monoamine re-uptake inhibitors with analgetic properties (imipramine, fluoxetine) potentiated the inhibitory effect of cortical stimulation. Adrenoceptor, dopamine, acetylcholine, GABA-receptor agents and antagonists of NMDA receptors had minor or no effect. Among non-narcotic analgesics, inhibitors of cyclooxygenase, metamysole and ketorolak increased only moderately the descending cortical control of nociception. Thus, the cerebral cortex is able to control the nociceptive processing in different pain syndromes (somatic, visceral or neuropathic pain). Opioidergic and serotonergic systems play the key role in this control. The effect over the cortical descending control is likely to be one of the components of the analgetic effect exerted by opioids and some other central analgesics.

Effects of electrical stimulation of the tooth pulp and phrenic nerve fibers on C1 spinal neurons in the rat.

Effects of electrical stimulation of the ipsilateral tooth pulp (TP) on C1 spinal neurons were determined in 33 anesthetized rats. One hundred and seven neurons responded to TP stimulation. In 10 rats, the activity of 18 C1 spinal neurons and the amplitude of a digastric electromyogram (dEMG, n = 10) increased proportionally during the TP stimulation at an intensity of 1-3 times the threshold for jaw-opening reflex (JOR). Excitatory receptive somatic fields were examined in 61 neurons. Somatic field locations of many neurons (67.2%) involved the ipsilateral face, neck, and jaw. The activity of 45 neurons was increased by both noxious pinch and brushing hair. Of the 107 C1 spinal neurons responding to TP stimulation, 55 were tested to determine the effects of electrical stimulation of the ipsilateral phrenic nerve (PN) above the heart. Twenty-eight of 55 neurons tested were excited; no change in activity was seen for the remaining 27 neurons. The activity of six neurons increased as the intensity of PN stimulation was increased. Excitatory receptive somatic fields were determined in 28 neurons, and somatic field locations of 17 neurons (60.7%) included the ipsilateral face, neck, and jaw. Both noxious pinch and brushing hair excited all 28 neurons. These results suggest that there may be the convergence of face, neck, jaw, TP, and PN afferents on the same C1 spinal neurons in the rat.

Effects of RPR 100893, a potent NK1 antagonist, on the jaw-opening reflex in the guinea pig

RPR 100893 appears as a new potent NK1 selective non-peptide antagonist both in vitro and in vivo, and exhibits high affinity for guinea pig and human NK1 receptor [M. Tabart, J.-F. Peyronel, Synthesis of RPR 100893, prototype of a new series of potent and selective non-peptide NK1 antagonists: the triarylperhydroisoindolols, Bioorg. Med. Chem. Lett., 4 (1994) 673–676.]. Intra-oral administration of RPR 100893 (3, 15, 10, 30 mg/kg) was performed in freely moving guinea pigs during recording of the short- (6–10 ms) and long-latency (18–26 ms) jaw-opening reflex (JOR) elicited by electrical stimulation (0.5 Hz) of the lower incisor tooth pulp. RPR 100893 induced a noticeable and dose-dependent increase of the long-latency reflex thresholds ( P<0.001) but was ineffective on the short-latency responses ( P=0.14). The results suggest that, in guinea pigs, the long-latency JOR requires activation of NK1 receptors, while the earlier reflex component, elicited by activation of periodontal afferents, does not. These NK1 receptors could be located either on JOR interneurons activated by tooth pulp afferents or on digastric motoneurons, receiving the tooth pulp input through a polysynaptic pathway.

Hydromorphone analgesia after intravenous bolus administration

This study investigated the analgesic effects of three intravenous bolus doses of hydromorphone (10, 20, 40 μg/kg) on experimental pain measures in normal humans. Ten healthy male volunteers participated in four study sessions, one for each of the hydromorphone doses as well as a placebo (saline). They received the four treatments in counterbalanced order under double-blind conditions and with study days at least 1 week apart. During each session subjects underwent repeated electrical tooth pulp stimulation at intensities sufficient to elicit a rating of `strong pain' before drug administration. Subjective pain reports (PRs) and dental evoked potential amplitude measures (EPs) served as analgesic effect indicators. We observed dose-dependent analgesia as measured by both PR ( P=0.009) and EP ( P=0.017). Area under the PR versus time curve as well as the EP versus time curve decreased in a log dose-dependent fashion. Although the peak effect was poorly defined, the onset of analgesia was rapid, within 5 min, and maximum analgesic effect was seen between 10 and 20 min after maximum plasma hydromorphone concentration. However, within sessions we found a poor correspondence between hydromorphone plasma concentration and effect. Compared to pain report data from other human studies done in our laboratory, hydromorphone has a shorter time to peak effect compared to morphine, and overall, hydromorphone hydrochloride is approximately five times as potent as morphine sulfate on a milligram basis.

Blood flow increase in the orofacial area of humans induced by painful stimulation

The purpose of this study was to investigate if painful stimulation produces blood flow changes in the tooth pulp and the facial skin in humans. Also, we attempted to find out if the possible blood flow changes induced by painful stimulation could be explained by central sympathetic and parasympathetic reflex mechanisms, by an antidromic activation of nociceptive axons (axon reflex), or by a change in central cardiovascular parameters. Laser Doppler flowmeter was used to assess the blood flow changes. Electrical tooth pulp stimulation at painful intensities induced a blood flow increase in the ipsilateral lip adjacent to the stimulus site, and vice versa. Nonpainful stimulation had no effects. Painful thermal stimulation of the upper lip also produced an increase in the blood flow of the ipsilateral upper incisor. The blood flow changes in the lip produced by dental stimulation were not correlated with changes in systemic blood pressure or heart rate. Painful electrical stimulation of the hand did not induce any changes in the pulpal blood flow, whereas painful dental stimulation produced a blood flow decrease in the finger but no change in the contralateral lip or cheek. In monkey experiments a regional block of the central conduction of the inferior alveolar nerve at the level of the mandibular foramen produced varying results: the blood flow increase in the lower incisor produced by noxious thermal stimulation of the ipsilateral lower lip was not abolished in two experiments but was abolished in other two experiments. It is concluded that painful stimulation can induce significant increases in the blood flow of the orofacial regions in humans. This increase is predominantly restricted to the region adjacent to the stimulus site and cannot be explained by changes in the central cardiovascular parameters. Central neuronal reflex mechanisms and an axon reflex may both underlie these blood flow increases.

Electrical stimulation of tooth pulp increases the expression of c-fos in the cat supraoptic nucleus but not in the paraventricular nucleus

Immunoreactivity to Fos protein was detected in the supraoptic (SON) and para-ventricular (PVN) nuclei of the cat using immunohistochemical methods. In the intact animal group, only a few Fos-positive neurons were observed in the PVN, but the SON did not contain any positive neurons. Intraperitoneal injection of pentobarbital sodium (Nembutal: 35 mg/kg) induced c-fos expression in the SON, but not in the PVN. Electrical stimulation of tooth pulp with an intensity that was 3 times the threshold of the jaw-opening reflex (200–600 μA) increased the number of Fos-positive neurons in the SON by up to 388% as compared with those of the Nembutal group, whereas the stimulation did not alter the number in the PVN. The increase was observed throughout the extent of the SON. In addition, morphine treatment (2 mg/kg, i.p.), 5 minutes before tooth pulp stimulation, considerably inhibited the increase in the SON. There were no significant differences among the 3 groups (intact, Nembutal, morphine) in the number of positive neurons in the PVN. These findings suggest that these hypothalamic nuclei have different functional roles and that the SON is involved in nociception and/or the consequent emotional and visceral reactions.

Expression of Fos protein in the cat forebrain induced by the electrical stimulation of tooth pulp.

Expression of Fos protein in the cat forebrain induced by the electrical stimulation of tooth pulp.

Induction of the c-fos proto-oncogene by electrical stimulation of tooth pulp in the cat forebrain

Induction of the c-fos proto-oncogene by electrical stimulation of tooth pulp in the cat forebrain

Distribution and response properties of cat SI neurons responsive to changes in tooth temperature

1. The activity of 214 tooth pulp-driven neurons (TPNs) in the primary somatosensory cortex (SI) activated by electrical stimulation of the canine tooth pulp was studied in anesthetized cats. These neurons were tested for their responses to thermal stimulation of the tooth pulp. 2. One hundred fifty-five TPNs were not responsive to changes in tooth temperature (thermally insensitive, TINS-TPNs) and 59 TPNs were responsive (thermally sensitive, TS-TPNs: 38 TS-TPNs were heat sensitive and 21 were cold sensitive). TS-TPNs were also tested for responsiveness to mechanical and thermal stimulation of the skin, mucosa, or periodontal membrane. Each TS-TPN was classified on the basis of cutaneous, mucosal, or periodontal mechanical receptive-field properties as either low-threshold mechanoreceptive (LTM: 57%), wide dynamic range (WDR: 25%), nociceptive specific (NS: 10%) or pulp specific (PS: 8%). 3. TS-TPNs were distributed in an upper bank of the orbital sulcus of SI. The majority were located in laminae III (32%) and IV (60%) of area 3b. 4. Heat-sensitive LTM, WDR, PS TS-TPNs, and cold-sensitive LTM TS-TPNs were characterized by a rapid rise in firing rate during thermal stimulation of the tooth pulp. In contrast, heat-sensitive NS and cold-sensitive NS and PS TS-TPNs responded with a slow rise in firing frequency during thermal stimuli delivered to the tooth pulp. 5. A linear regression analysis was applied to the stimulus-response functions of neuronal discharges of TS-TPNs. Fifty-six percent of heat-sensitive LTM, WDR, and cold-sensitive LTM TS-TPNs showed statistically significant relation (P less than 0.5) between peak firing frequency and stimulus temperature and increasing firing frequency after increases in stimulus temperature, whereas heat-sensitive and cold-sensitive NS and PS TS-TPNs did not show a clear increase in firing frequency during the thermal stimulus. 6. These findings suggest that heat-sensitive LTM and WDR TS-TPNs and cold-sensitive LTM TS-TPNs that showed high regression coefficients in stimulus-response function may be involved in encoding the intensity of noxious thermal stimulation of the tooth pulp.

Properties of single neurons in the cat midsuprasylvian gyrus

Responses of cells in the midsuprasylvian gyrus (MSSG) of cats were investigated following electrical stimulation of the central lateral nucleus (CL) of the thalamus and tooth pulp, low-threshold cutaneous or visual afferents. Electrical stimulation in CL induced excitation in many cells located in cortical areas 5 and 7. Cells in these areas also received input from somato-sensory and visual afferents. Cells in MSSG showed a wide convergence from tooth pulp, low-threshold cutaneous afferents and from the CL. The majority of wide convergent cells in area 5 were found in layers IV and V, while cells excited by CL and tooth pulp were found in layers II and III. Similarities were found between CL and tooth pulp evoked responses with regard to the excitation-inhibition pattern. The excitation evoked from CL and tooth pulp was less often followed by a hyperpolarizing potential compared to that seen after low-threshold lip, paw and visual afferent stimulation. Stimulation sites in the lateral parts of CL-evoked responses with the shortest latencies in area 5. In this part of the cortex, short latency synaptic potentials were found in cells in superficial layers. In the same area, synaptic potentials of short latency were also evoked by electrical stimulation of tooth pulp, lip and paw. Light-flash stimulation evoked responses with the shortest latencies in area 7. The results of this study demonstrate that putative nociceptive information reaches the parietal association cortex and that part of this input may be relayed via CL. We suggest that the excitatory influences of nociceptive and CL stimulation is related to behavioral arousal and attention mechanisms.