naloxone and Toothache

Pentazocine can be a useful analgesic agent for the management of acute dental pain. It has both central and peripheral opioid activity. In clinical trials, analgesic compounds containing pentazocine have been shown to effectively relieve moderate-to-severe pain. It is an appropriate analgesic for the codeine-sensitive patient. Because of a change in formulation, the potential for abuse has been minimized. Although there is a possibility that the drug may have a psychotomimetic effect, the incidence is low and should not preclude use. Analgesic compounds containing pentazocine are clinically appropriate for the management of surgically induced dental pain.

Topics: Analgesics; Drug Combinations; Facial Pain; Humans; Naloxone; Pain, Postoperative; Pentazocine; Receptors, Opioid; Tooth Extraction; Toothache

The purpose of this prospective clinical trial was to investigate the analgesic efficacy of three oral medication groups on postoperative endodontic pain in male and female dental patients, with an emphasis on analgesic differences between the sexes. Forty-three patients were administered ibuprofen 600 mg, placebo, or pentazocine 50 mg/0.5 mg naloxone in a randomized, double-blinded manner. Beginning immediately after endodontic treatment, patients took the assigned medication every 6 hours for 24 hours and recorded their degree of discomfort on a 100-mm visual analog scale. Statistical analysis of the data showed that ibuprofen 600 mg provided statistically significantly greater analgesia than placebo at 6 and 12 hours (P = 0.0014 and 0.0024), and pentazocine/naloxone provided statistically significantly greater analgesia than placebo at 12 hours (P = 0.0084). Sex-dependent differences were noted within the pentazocine/naloxone group, which showed significantly greater analgesia in females compared with males (P = 0.007).

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Double-Blind Method; Drug Combinations; Female; Humans; Ibuprofen; Likelihood Functions; Linear Models; Male; Naloxone; Pain Measurement; Pain, Postoperative; Pentazocine; Periapical Periodontitis; Prospective Studies; Pulpitis; Root Canal Therapy; Sex Factors; Surveys and Questionnaires; Toothache

A series of double-blind, placebo-controlled clinical trials demonstrated that low doses of morphine (0.4, 1.2, and 3.6 mg) administered into the intraligamentary space of a chronically inflamed hyperalgesic tooth produced a dose-related naloxone-reversible analgesia. This analgesic effect is mediated by a local mechanism in the inflamed tissue, because subcutaneous administration of a 1.2 mg dose of morphine failed to elicit an analgesic response. In contrast, submucosal administration of 1.2 mg morphine or 50 microg fentanyl to the site of extraction of an impacted third molar after the onset of acute pain failed to elicit an analgesic response despite demonstration of a sensitive bioassay. These data indicate that peripheral opioid analgesia can be evoked in a model of chronic, but not acute, inflammatory pain, suggesting a temporal dependent mechanism needed for the expression of peripheral opiate analgesia during inflammation in humans.

Topics: Acute Disease; Adult; Analgesics, Opioid; Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fentanyl; Humans; Injections; Male; Mepivacaine; Morphine; Naloxone; Pain Measurement; Pain, Postoperative; Periodontitis; Time Factors; Tooth Extraction; Toothache; Treatment Outcome

A modified double-blind evaluation of naloxone reversibility of dental analgesia produced by auricular electrical stimulation (AES) was examined in 40 subjects assigned randomly to one of four groups: AES followed by saline (AS), AES followed by naloxone (AN), placebo AES followed by saline (PS), and placebo AES followed by naloxone (PN). Dental pain threshold was tested using a hand-held dental pulp tester. A second investigator administered the true or placebo AES using an electrical stimulator. A third investigator injected intravenously saline or naloxone. The subjects and investigators 1 and 3 were blind to all treatment conditions. A repeated measures analysis of variance revealed a significant difference among the four groups. The AES groups exhibited a statistically significant 18% elevation of pain threshold, whereas the two placebo stimulation groups (PS and PN) remained essentially unchanged. The mean pain threshold increased to more than 23% for group AS, but fell to less than 12% for the subjects in group AN, who were given naloxone. These findings indicate a small but significant elevation of pain threshold by AES, an effect partially blocked by naloxone, suggesting an endogenous opioid system as one mechanism for AES analgesia.

Topics: Acupuncture Analgesia; Acupuncture Points; Adolescent; Adult; Analysis of Variance; Anesthesia, Dental; Dental Pulp Test; Double-Blind Method; Ear, External; Electric Stimulation; Female; Humans; Male; Naloxone; Pain Threshold; Toothache

The purpose of this study was to examine in man the analgesic effect of non-segmental electroacupuncture (EA) limited to a single point (Hoku hand point) and the influence of naloxone using an original modified electrical dental pain test. Results in the literature are still contradictory as to the degree and specificity of acupuncture analgesia and its opioid nature. Acupuncture techniques as well as experimental pain models are factors accounting for the discrepancies in the results. For this reason, we designed an experimental pain test characterized by a high degree of specificity, validity and reliability. We chose optimal conditions for eliciting specific acupuncture effect, i.e. non-segmental, low frequency and painful intensity range. A cross-over repeated measure experimental design was used. Five normal trained subjects participated in 65 sessions under four conditions (control, EA, EA+naloxone, EA+placebo). Changes in experimental dental pain thresholds served as indices of analgesia. The results indicated a 27% pain threshold increase after 30 minutes of EA stimulation (p less than .0001), with no differential effect between pain detection (mild pain sensation) and pain discomfort (strong pain sensation). This increase was partially blocked by the double blind injection of 0.8 mg naloxone IM (p less than .005). The experiment was designed in such a way as to prevent the occurrence of a stress analgesic effect. The endogenous opioid system was shown to be partially involved in acupuncture analgesia. Other mechanisms of action are discussed in view of the literature findings.

Topics: Acupuncture Therapy; Adult; Analgesia; Female; Humans; Naloxone; Sensory Thresholds; Toothache

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.

Topics: Afferent Pathways; Anesthetics, Local; Animals; Dental Pulp; Dizocilpine Maleate; Dorsomedial Hypothalamic Nucleus; Efferent Pathways; Excitatory Amino Acid Antagonists; Gene Expression Regulation; Hyperalgesia; Irritants; Lidocaine; Male; Molar; Mustard Plant; Naloxone; Narcotic Antagonists; Neuronal Plasticity; Plant Oils; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; RNA, Messenger; Sensory Receptor Cells; Toothache

Clinically, acupuncture therapy is useful for the control of acute or chronic pain. This study was designed to elucidate the antinociceptive mechanism of acupuncture and the mechanisms underlying cardiovascular reflex elicited by toothache. Expression of c-Fos, a neuronal activation marker, and the phenylethanalamine-N-methyltransferase (PNMT) were examined 1.5 hours after noxious intrapulpal tooth stimulation. Manual acupuncture was performed 20 min before noxious intrapulpal stimulation by 2 M KCl injection into upper or lower anterior tooth pulp. The acupuncture points were Li4 (Hegu) between the 1st and 2nd metacarpal bones or St36 (Zusanli) between the anterior crest of the tibial tuberosity and the fibula head below the patella. After noxious intrapulpal tooth stimulation, Fos-immunoreactive (IR) neurons were identified in the trigeminal subnucleus caudalis (Vc) and the transitional region between the subnucleus caudalis and the subnucleus interpolaris (Vi), in the inferior olivory nucleus (IO) connecting the cerebellum and other brain regions, and also the thalamic ventral posteromedial (VPM) nucleus and centrolateral (CL) nucleus, respectively. In addition, Fos-IR neurons were found in the central cardiovasuclar regulation centers, such as the hypothalamus supraoptic nucleus (SON) and paraventricular nucleus (PVN), and nucleus tractus solitarius (NTS) and rostral ventromedulla (RVLM). All acupuncture at St36 or Li4 significantly suppressed Fos-IR neurons in all Fos-expressed brain areas except the IO nucleus and attenuated the increases in arterial blood pressure (BP) and heart rate (HR) after noxious intrapulpal stimulation. Its Fos-suppressive effects were mostly blocked by naloxone, an opioid antagonist. In addition, acupuncture at St36 or Li4 significantly decreased Fos-containing PNMT, and this effect was also reversed by naloxone. These results suggest that: 1) tooth pulpal noxious signals transmit to the Vc and Vc/Vi transitional region and the 2nd afferent neuron synapse in the thalamic VPM and CL, 2) tooth pulpal pain elicits cardiovascular reflex mediated by NTS, VLM, hypothalamic SON and PVN, and 3) acupuncture reduces cardiovascular reflex elicited by toothache, is associated with the adrenergic system.

Topics: Acupuncture Points; Acupuncture Therapy; Animals; Blood Pressure; Brain; Dental Pulp; Heart Rate; Male; Naloxone; Narcotic Antagonists; Needles; Neurons; Nociceptors; Phenylethanolamine N-Methyltransferase; Physical Stimulation; Potassium Chloride; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Stimulation, Chemical; Toothache

Animal models simulating acute human pulpitis are still lacking. The rat incisors present a particular situation where most of their innervation is considered to be unmyelinated and concentrated mainly in the tooth pulp. This study reports on a new model for dental pain induced by inflammatory agents applied to the tooth pulps of incisors. In different groups of rats, artificial crowns were fixed on the lower incisors, after cutting 1-2mm of their distal extremities. A volume of 7-10 microl of solutions of saline, capsaicin (1-10mg/ml) or formalin (2.5% or 5%) was injected in the crown cavity, and the nociceptive behaviour was quantitated following a devised scoring method of four scales. Intradental application of capsaicin produced nociceptive scores in the form of one plateau for 1-2h depending on the concentration used. Similar results were obtained with intradental application of formalin 2.5%. The one plateau of nociceptive scores obtained with formalin contrasts with the biphasic aspect of nociceptive behaviour described with the intradermal formalin test. This discrepancy could be attributed to a difference in the types of afferent fibres involved in each situation. Pretreatment with morphine (2 mg/kg) attenuated, in a naloxone-reversible manner, the nociceptive behaviour observed following intradental application of capsaicin. Pretreatment with meloxicam (a cyclo-oxygenase-2 inhibitor) exerted a less pronounced attenuation of the nociceptive scores when compared with morphine. These results provide evidence for the validity of the described model for the simulation of tooth pulp inflammatory pain in awake animals.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Capsaicin; Crowns; Cyclooxygenase Inhibitors; Dental Pulp Cavity; Disease Models, Animal; Drug Interactions; Female; Formaldehyde; Gingiva; Inflammation; Male; Meloxicam; Morphine; Naloxone; Narcotic Antagonists; Nerve Fibers; Nociceptors; Pain Measurement; Rats; Rats, Sprague-Dawley; Thiazines; Thiazoles; Toothache

The effect of cyproheptadine on growth hormone (GH) secretion and dental pain threshold elevation during physical exercise was studied in healthy human subjects. Different levels of exercise (200-300 W) were produced by a cycle-ergometer. Dental pain thresholds were tested with a constant current pulp tester. In all 6 subjects dental pain thresholds and the heart rate were increased with increasing work load. Cyproheptadine did not have any significant effect on dental pain threshold elevations, although it suppressed the exercise-induced GH release. The results indicate that the exercise-induced dental pain threshold elevation is not based on GH-related stress mechanisms, since cyproheptadine did not reverse the pain threshold elevation.

Topics: Adult; Cyproheptadine; Growth Hormone; Heart Rate; Humans; Male; Naloxone; Physical Exertion; Pituitary Gland, Anterior; Sensory Thresholds; Toothache

Responses induced by tooth pulp stimulation were studied in 27 gallamine immobilized adult cats. Single units were recorded from the amygdala using stainless steel microelectrodes. Of 57 amygdaloid neurons, 8 were responsive to only non-nociceptive (tap and/or hair bending) stimuli, 7 were responsive to both nociceptive (pinch) and non-nociceptive stimuli, 18 were responsive to nociceptive stimuli, non-nociceptive stimuli and tooth pulp stimulation, and the others did not respond to these stimuli. The neurons in the amygdala responsive to tooth pulp stimulation were localized in the nucleus amygdaloideus centralis (pars lateralis) [Acl], nucleus amygdaloideus centralis (pars medialis) [Acl] and nucleus amygdaloideus basalis (pars magnocellularis) [Abm]. The response induced by tooth pulp stimulation was depressed by morphine and reversed by naloxone. These results suggest that Acl, Acm and Abm in the amygdala may receive pain sensation evoked by tooth pulp stimulation. Moreover, there is a possibility that these nuclei may be related to the emotional component involved in nociceptive processing.

Topics: Afferent Pathways; Amygdala; Animals; Brain Mapping; Cats; Dental Pulp; Endorphins; Evoked Potentials, Somatosensory; Female; Male; Morphine; Naloxone; Nociceptors; Toothache

The effect of acupuncture on pain threshold from tooth pulp stimulation was studied in alert, awake monkeys. Manual manipulation of acupuncture needles in specific acupuncture points in the hands and legs caused a consistent and significant rise in threshold. Some points, such as Ho-Ku (LI-4) and Tsu-San-Li (St-36), produced more prominent analgesic effects than others. Increase of pain threshold was observed also after application of finger pressure on acupuncture points. Acupuncture and finger pressure applied to certain muscle points exhibited similar analgesic effects.

Topics: Acupuncture Therapy; Animals; Dental Pulp; Endorphins; Haplorhini; Naloxone; Pain; Toothache