naloxone and Facial-Pain

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

Twenty-eight patients suffering acute pain following operative removal of impacted third molars took part in the present study. In 20 patients who reported pain reduction exceeding 25% of the initial pain intensity during vibratory stimulation (100 Hz) or TENS (2 or 100 Hz), only 1 patient (given 2 Hz TENS) reported pain increase after injection of 0.8 mg naloxone (i.v.). In 8 patients, not treated with afferent stimulation, 2 experienced increase in pain intensity after naloxone injection. The results show that pain relief using TENS or vibration is not influenced by naloxone.

Topics: Acute Disease; Adolescent; Adult; Clinical Trials as Topic; Electric Stimulation Therapy; Facial Pain; Female; Humans; Male; Mouth Diseases; Naloxone; Pain, Postoperative; Tooth, Impacted; Transcutaneous Electric Nerve Stimulation; Vibration

Pulpal pain is a common orofacial health issue that has been linked to cognitive impairment. Because of its prominent role in pain modulation and cognitive impairment, apelin (Apl) is regarded as a promising target for clinical pain management. The role of Apl in orofacial pain, however, is unknown. The purpose of this study was to determine the effects of intra-periaqueductal grey matter (PAG) administrations of Apl-13 on capsaicin-evoked pulpal nocifensive behaviour and capsaicin-induced spatial learning and memory impairments in rats.. Forty-nine male Wistar rats (200-250 g) were randomly divided into seven groups (n = 7 per group). The groups included: untreated intact, capsaicin (Caps) only, three Caps+Apl groups that received different dosages of intra-PAG injection of Apl-13 (1, 2 and 3 μg/rat) 20 min prior to capsaicin application, and two Apl+antagonist groups that received Apl receptor antagonist or naloxone (a μ opioid receptor) 20 min before Apl injection. Learning and memory were assessed using the Morris water maze test. One-way analysis of variance followed by Tukey post hoc tests was used for statistical analysis.. Intra-PAG administration of Apl-13 significantly reduced the capsaicin-induced nocifensive behaviour (p < .01). This antinociception effect was inhibited by F13A and naloxone. Apl-13 inhibited nociception-induced learning and memory deficits (p < .01). The cognitive effects were also blocked by pre-treatment administration of F13A (3 μg/rat).. These findings indicated that Apl-13, via Apl receptors (AR or APJ) and μ opioid receptors, alleviated capsaicin-induced dental nocifensive behaviour and protected against nociception-induced learning and memory impairments. As a result of our findings, Apl appears to be a promising analgesic option for further research in orofacial pain models and clinical trials.

Topics: Animals; Apelin; Capsaicin; Facial Pain; Male; Memory Disorders; Naloxone; Periaqueductal Gray; Rats; Rats, Wistar; Spatial Learning

Tapentadol exhibits a synergistic dual effect effect (MOR / NRI) -agonist effect on noradrena-line reuptake inhibition (NRI). Tapentadol is effective on pain with neuropathic characteristics, therefore we decided to use it in an experimental model of acute orofacial pain.. The Orofacial Stimulation Test, developed by Ugo Basile, measures hypersensitivity to thermal or mechanical stimulation of the trigeminal area. In the experiment, rats had to voluntarily contact a thermal or mechanical stimulator with their unshaved vibrissal pad in order to access a food reward. Twenty adult laboratory rats (average weight 345 grams) were tested. Intraperitoneal tapentadol was used in doses of 1 mg/kg and 2 mg/kg.. The results of the pilot study indicate that intraperitoneal administration of tapentadol (2 mg/kg) increased mechanical anti-nociception in rats.

Topics: Acute Pain; Analgesics, Opioid; Animals; Central Amygdaloid Nucleus; Dose-Response Relationship, Drug; Facial Pain; Naloxone; Pain Measurement; Pilot Projects; Rats; Tapentadol; Yohimbine

Endomorphin-2 demonstrates potent antinociceptive effects in various pain models. The objectives of the present study were to explore the role of endomorphin-2 in the modulation of orofacial pain induced by orthodontic tooth movement in rats. An orthodontic pain model was established in male Sprague-Dawley rats by ligating coiled springs to mimic orthodontic force (40 g). On days 0, 1, 3, 5, 7, and 14 following orthodontic tooth movement, bite force was recorded as a surrogate measure of orthodontic pain. Ipsilateral trigeminal ganglia, trigeminal nucleus caudalis, and periodontal tissues were harvested for immunostaining. Endomorphin-2, endomorphin-2 + naloxone (a non-selective opioid receptor antagonist), naloxone, and saline were injected into trigeminal ganglia and periodontal tissues to explore the role of endomorphin-2 on orthodontic pain. The results showed that following orthodontic tooth movement, endomorphin-2 expression levels in trigeminal ganglia were elevated on days 1, 3, 5, and 7. Orthodontic pain levels were increased on days 1, 3, and 5. The administration of endomorphin-2 into both trigeminal ganglia and periodontal tissues alleviated orthodontic pain. Moreover, the effects of endomorphin-2 could be blocked by naloxone completely in trigeminal ganglia but only partially in periodontal tissues. Therefore, endomorphin-2 plays an important role in the modulation of orthodontic pain both centrally and peripherally, probably through different pathways.

Topics: Animals; Facial Pain; Male; Naloxone; Oligopeptides; Rats; Rats, Sprague-Dawley; Tooth Movement Techniques; Trigeminal Ganglion

Mimosa tenuiflora (Willd.) Poiret, popularly known in Brazil as "jurema-preta" is widely used against bronchitis, fever, headache and inflammation. Its antioxidant, anti-inflammatory and antinociceptive potential has already been reported. To assess the orofacial antinociceptive effect of M. tenuiflora, ethanolic extracts of M. tenuiflora (leaves, twigs, barks and roots) were submitted to in vitro tests of antioxidant activity. The extract with the highest antioxidant potential was partitioned and subjected to preliminary chemical prospecting, GC-MS, measurement of phenolic content and cytotoxicity tests of the fraction with the highest antioxidant activity. The nontoxic fraction with the highest antioxidant activity (FATEM) was subjected to tests of acute and chronic orofacial nociception and locomotor activity. The possible mechanisms of neuromodulation were also assessed. The EtOAc fraction, obtained from the ethanolic extract of M. tenuiflora barks, was the one with the highest antioxidant potential and nontoxic (FATEM), and Benzyloxyamine was the major constituent (34.27%). FATEM did not alter the locomotor system of mice and reduced significantly the orofacial nociceptive behavior induced by formalin, glutamate, capsaicin, cinnamaldehyde or acidic saline compared to the control group. FATEM also inhibited formalin- or mustard oil-induced temporomandibular nociception. In addition, it also reduced mustard oil-induced orofacial muscle nociception. However, FATEM did not alter hypertonic saline-induced corneal nociception. Neuropathic nociception was reversed by treatment with FATEM. The antinociceptive effect of FATEM was inhibited by naloxone, L-NAME and glibenclamide. FATEM has pharmacological potential for the treatment of acute and neuropathic orofacial pain and this effect is modulated by the opioid system, nitric oxide and ATP-sensitive potassium channels. These results lead us to studies of isolation and characterization of bioactive principles.

Topics: Acrolein; Analgesics; Animals; Antioxidants; Capsaicin; Chemical Fractionation; Chlorocebus aethiops; Ethanol; Facial Pain; Glutamic Acid; Glyburide; Mice; Mimosa; Motor Activity; Naloxone; NG-Nitroarginine Methyl Ester; Nociception; Phenols; Plant Extracts; Rats, Wistar; Temporomandibular Joint; Vero Cells

The aim of this study was to evaluate the antinociceptive effect of Kaempferol-3-O-rutinoside (KR), isolated from the plant Ouratea fieldingiana, on the orofacial nociception and possible mechanisms of action. Adult zebrafish (Danio rerio) were tested as a behavioral model to study formalin, glutamate, capsaicin, cinnamaldehyde and acidic saline-induced orofacial nociception, using as parameter the number of times the fish crossed the lines between the quadrants of a glass Petri dish during a specific time. Morphine was used as positive control. The effect of KR was tested for modulation by opioid (naloxone), nitrergic (L-NAME), TRPV1 (ruthenium red), TRPA1 (camphor) or ASIC (amiloride) antagonists. The effect of KR on zebrafish locomotor behavior was evaluated with the open field test. KR did not alter the fish's locomotor system and significantly reduced the orofacial nociceptive behavior induced by all noxious agents compared to the control group. The antinociceptive effect of KR was similar to morphine. All antagonists inhibited the antinociceptive effect of KR. KR has pharmacological potential for the treatment of acute orofacial pain and this effect is modulated by the opioid and nitrergic systems as well as TRPV1, TRPA1 and ASIC channels. These results can lead to the development of a new natural product for the treatment of orofacial pain and confirm the popular use of O. fieldingiana leaf for pain relief.

Topics: Analgesics; Analgesics, Opioid; Animals; Behavior, Animal; Disease Models, Animal; Facial Pain; Female; Kaempferols; Male; Morphine; Naloxone; Nociception; Ochnaceae; Plant Leaves; Zebrafish

In the present study, we investigated the effects of microinjection of vitamin B

Topics: Analgesics; Animals; CA1 Region, Hippocampal; Catheters, Indwelling; Disease Models, Animal; Dose-Response Relationship, Drug; Exploratory Behavior; Facial Pain; Formaldehyde; Male; Maze Learning; Memory Disorders; Microinjections; Motor Activity; Naloxone; Narcotic Antagonists; Nootropic Agents; Rats, Wistar; Scopolamine; Vibrissae; Vitamin B 12

To investigate whether the protective effect of testosterone on the development of temporomandibular joint (TMJ) nociception in male rats is mediated by the activation of central opioid mechanisms.. Experiments were performed on 156 male Wistar rats. A pharmacologic approach was used to assess the ability of opioid receptor antagonists infused into the dorsal portion of the brainstem and adjacent to the caudal component (subnucleus caudalis) of the spinal trigeminal nucleus to block the protective effect of testosterone in male rats. The TMJ injection of 0.5% formalin was used as a nociceptive stimulus. One-way or two-way ANOVA was used for data analyses.. The injection of 0.5% formalin into the TMJ induced a significant nociceptive behavior in gonadectomized male rats (P < .05), but not in naïve, sham, and testosterone-replaced gonadectomized rats, confirming that testosterone prevents the development of TMJ nociception. The injection of either the nonselective opioid receptor antagonist naloxone (15 μg) or the simultaneous injection of the μ-opioid receptor antagonist Cys2, Tyr3, Orn5, Pen7amide (CTOP, 30 μg) and the κ-opioid receptor antagonist Nor-Binaltorphimine (Nor-BNI, 90 μg) significantly increased the 0.5% formalin-induced behavioral response in sham and testosterone-replaced gonadectomized rats (P < .05) but had no effect in gonadectomized rats. However, the injection of each selective opioid receptor antagonist alone or the simultaneous injection of μ- or κ- and δ-opioid receptor antagonists had no effect.. These findings indicate that the protective effect of endogenous testosterone on the development of TMJ nociception in male rats is mediated by the activation of central opioid mechanisms. Furthermore, the coactivation of central μ- and κ-opioid receptors is necessary for testosterone to protect male rats from developing TMJ nociception.

Topics: Animals; Brain Stem; Facial Pain; Formaldehyde; Male; Naloxone; Naltrexone; Narcotic Antagonists; Nociception; Nociceptive Pain; Orchiectomy; Rats; Rats, Wistar; Receptors, Opioid, kappa; Receptors, Opioid, mu; Somatostatin; Temporomandibular Joint; Temporomandibular Joint Disorders; Testosterone; Trigeminal Caudal Nucleus

Nicotinic acetylcholine and opioid receptors are involved in modulation of pain. In the present study, we investigated the effects of microinjection of nicotinic acetylcholine and opioid compounds into the ventral orbital cortex (VOC) on the formalin-induced orofacial pain in rats. For this purpose, two guide cannulas were placed into the left and right sides of the VOC of the brain. Orofacial pain was induced by subcutaneous injection of a diluted formalin solution (50μl, 1.5%) into the right vibrissa pad and face rubbing durations were recorded at 3-min blocks for 45min. Formalin produced a marked biphasic pain response (first phase: 0-3min and second phase: 15-33min). Epibatidine (a nicotinic receptor agonist) at doses of 0.05, 0.1 and 0.2μg/site, morphine (an opioid receptor agonist) at doses of 0.5, 1 and 2μg/site and their sub-analgesic doses (0.025μg/site epibatidine with 0.25μg/site morphine) combination treatment suppressed the second phase of pain. The antinociceptive effect induced by 0.2μg/site of epibatidine, but not morphine (2μg/site), was prevented by 2μg/site of mecamylamine (a nicotinic receptor antagonist). Naloxone (an opioid receptor antagonist) at a dose of 2μg/site prevented the antinociceptive effects induced by 2μg/site of morphine and 0.2μg/site of epibatidine. No above-mentioned chemical compounds affected locomotor activity. These results showed that at the VOC level, epibatidine and morphine produced antinociception. In addition, opioid receptor might be involved in epibatidine-induced antinociception, but the antinociception induced by morphine was not mediated through nicotinic acetylcholine receptor.

Topics: Analgesics, Opioid; Animals; Bridged Bicyclo Compounds, Heterocyclic; Drug Therapy, Combination; Facial Pain; Formaldehyde; Locomotion; Male; Mecamylamine; Microinjections; Morphine; Naloxone; Narcotic Antagonists; Nicotinic Agonists; Nicotinic Antagonists; Pain Measurement; Prefrontal Cortex; Pyridines; Rats

Histamine and opioid systems are involved in supraspinal modulation of pain. In this study, we investigated the effects of separate and combined microinjections of agonists and antagonists of histamine H1 and H2 and opioid receptors into the thalamic submedius (Sm) nucleus on the formalin-induced orofacial pain. Two guide cannulas were implanted into the right and left sides of the Sm in ketamine- and xylazine-anesthetized rats. Orofacial formalin pain was induced by subcutaneous injection of a diluted formalin solution (50 μl, 1.5%) into the vibrissa pad. Face rubbing durations were recorded at 3-min blocks for 45 min. Formalin produced a biphasic pain response (first phase: 0-3 min and second phase: 15-33 min). Separate and combined microinjections of histamine H1 and H2 receptor agonists, 2-pyridylethylamine (2-PEA) and dimaprit, respectively, and opioid receptor agonist, morphine, attenuated the second phase of pain. The analgesic effects induced by 2-PEA, dimaprit, and morphine were blocked by prior microinjections of fexofenadine (a histamine H1 receptor antagonist), famotidine (a histamine H2 receptor antagonist), and naloxone (an opioid receptor antagonist), respectively. Naloxone also prevented 2-PEA- and dimaprit-induced antinociception, and the analgesic effect induced by morphine was inhibited by fexofenadine and famotidine. These results showed the involvement of histamine H1 and H2 and opioid receptors in the Sm modulation of orofacial pain. Opioid receptor might be involved in analgesia induced by activation of histamine H1 and H2 receptors and vice versa.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Facial Pain; Formaldehyde; Histamine Agonists; Histamine Antagonists; Male; Morphine; Naloxone; Narcotic Antagonists; Rats; Rats, Wistar; Receptors, Histamine H1; Receptors, Histamine H2; Receptors, Opioid; Thalamic Nuclei

The hippocampus is a region of the brain that serves several functions. The dopaminergic system acts through D1- and D2-like receptors to interfere in pain modulation and the opioid receptors play major roles in analgesic processes and there are obvious overlaps between these two systems. The present study investigated the interaction between the opioidergic and dopaminergic systems in the dorsal hippocampus (CA1) region for formalin-induced orofacial pain. Two guide cannulae were stereotaxically implanted in the CA1 region and morphine (0.5, 1, 2 and 4 μg/0.5 μl saline) and naloxone (0.3, 1 and 3 μg/0.5 μl saline) were used as the opioid receptor agonist and antagonist, respectively. SKF-38393 (1 μg/0.5 μl saline) was used as a D1-like receptor agonist, quinpirole (2 μg/0.5 μl saline) as a D2-like receptor agonist, SCH-23390 (0.5 μg/0.5 μl saline) as a D1-like receptor antagonist and sulpiride (3 μg/0.5 μl DMSO) as a D2-like receptor antagonist. To induce orofacial pain, 50 μl of 1% formalin was subcutaneously injected into the left side of the upper lip. Our results showed that different doses of morphine significantly reduced orofacial pain in both phases induced by formalin. Naloxone (1 and 3 μg) reversed morphine induced analgesia in CA1. SKF-38393 and quinpirole with naloxone (1 μg) significantly decreased formalin-induced orofacial pain in both phases. SCH-23390 had no effect on the antinociceptive response of morphine in both phases of orofacial pain. Sulpiride reversed the antinociceptive effects of morphine only in the first phase, but this result was not significant. Our findings suggest that there is cross-talk between the opioidergic and dopaminergic systems. Opioidergic neurons also exerted antinociceptive effects by modulation of the dopaminergic system in the CA1 region of the brain.

Topics: Animals; Benzazepines; CA1 Region, Hippocampal; Dopamine; Dopamine Agonists; Dopamine Antagonists; Facial Pain; Formaldehyde; Male; Naloxone; Narcotic Antagonists; Opioid Peptides; Rats; Rats, Wistar

The present study explored the interaction between histaminergic and opioidergic systems at the level of the hippocampus in modulation of orofacial pain by intra-hippocampal microinjections of histamine, pyrilamine (an antagonist of histamine H(1) receptors), ranitidine (an antagonist of histamine H(2) receptors), morphine (an opioid receptor agonist) and naloxone (an opioid receptor antagonist) in separate and combined treatments. Orofacial pain was induced by subcutaneous (sc) injection of formalin (50 μl, 1%) in the upper lip region and the time spent face rubbing was recorded in 3 min blocks for 45 min. Formalin (sc) produced a marked biphasic (first phase: 0-3 min, second phase: 15-33 min) pain response. Histamine and morphine suppressed both phases of pain. Histamine increased morphine-induced antinociception. Pyrilamine and ranitidine had no effects when used alone, whereas pretreatments with pyrilamine and ranitidine prevented histamine- and morphine-induced antinociceptive effects. Naloxone alone non-significantly increased pain intensity and inhibited the antinociceptive effects of morphine and histamine. The results of the present study indicate that at the level of the hippocampus, histamine through its H(1) and H(2) receptors, mediates orofacial region pain. Moreover, morphine via a naloxone-reversible mechanism produces analgesia. In addition, both histamine H(1) and H(2) receptors, as well as opioid receptors may be involved in the interaction between histamine and morphine in producing analgesia.

Topics: Analgesics, Opioid; Animals; Disease Models, Animal; Facial Pain; Formaldehyde; Hippocampus; Histamine; Male; Morphine; Naloxone; Pyrilamine; Rats; Rats, Wistar; Receptors, Histamine H1; Receptors, Histamine H2

To investigate the effects of morphine on mechanical allodynia following compression of the trigeminal ganglion in the rat.. Experiments were carried out on male Sprague-Dawley rats weighing between 250 and 260 g. For compression, a 4% agar solution (8 microL) was injected into the trigeminal ganglion. In the control group, rats were sham operated without agar injections. The authors evaluated the effects of intraperitoneal or intracisternal administration of morphine on mechanical allodynia evoked by air-puff stimulation of the vibrissa pad area 14 days following compression of the trigeminal ganglion.. Mechanical allodynia was established within 3 days and lasted beyond postoperative day 24. Intraperitoneal administration of morphine (2 or 5 mg/kg) significantly blocked mechanical allodynia ipsilateral to the compression of the trigeminal ganglion. Intraperitoneal administration of morphine also inhibited mechanical allodynia on the contralateral side. Moreover, intracisternal administration of morphine (5 microg) strongly suppressed both ipsilateral and contralateral mechanical allodynia. The antiallodynic effects of morphine were blocked by pretreatment with naloxone, an opioid receptor antagonist.. These results suggest that the application of a high dose of morphine may be of great benefit in treating trigeminal neuralgia-like nociception.

Topics: Animals; Cisterna Magna; Facial Pain; Injections; Injections, Intraperitoneal; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nerve Compression Syndromes; Physical Stimulation; Rats; Rats, Sprague-Dawley; Trigeminal Ganglion; Trigeminal Neuralgia; Vibrissae

The mechanism of orthodontic pain and discomfort is poorly understood partly because of the limited number of animal behavioral models for pain assessment. This study aimed to develop a behavioral model for assessment of tooth-movement pain in rats using directed face-grooming activity. Male Sprague-Dawley rats weighing 200-300 g were used. They were videotaped on days 1, 3, 5, 7, and 14 after experimental tooth movement and their directed face-grooming behavior was evaluated. In addition, we also evaluated behavioral responses to the application of a progressively higher magnitude force and to multiple applications of an equal magnitude force. Finally, the effects of peripherally and systemically administered morphine and of the N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801, on the behavioral responses were evaluated. The results indicated that time spent on directed face-grooming activity increased dramatically after initiating experimental tooth movement. The change concurred with the initial orthodontic pain response. This behavioral change was reproducible and was related to force magnitude. Application of both systemic and peripheral morphine and MK-801 could exert an analgesic effect on this pain model. These results suggest that directed face-grooming behavior can be a reliable measure for tooth-movement pain in rats, which could be widely used in investigating the orthodontic pain mechanism.

Topics: Animals; Dental Alloys; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Facial Pain; Grooming; Male; Morphine; Naloxone; Narcotic Antagonists; Narcotics; Nickel; Orthodontic Wires; Pain Measurement; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Stress, Mechanical; Time Factors; Titanium; Tooth Movement Techniques; Videotape Recording

The participation of opioids in the antinociceptive effect of electroacupuncture was evaluated in terms of nociception produced by thermal stimuli applied to the face of male Wistar rats, weighing 180-230 g. Electrical stimulation (bipolar and asymmetric square wave with 0.5 mA intensity for 20 min) of acupoint St36, located in the anterior tibial muscle 10 mm distal to the knee joint, induced antinociception in the present model, which was maintained for 150 min. Acupoint LI4, located in the junction of the first and second metacarpal bones, did not achieve antinociception at any frequency studied (5 Hz: 1.7 +/- 0.1; 30 Hz: 1.8 +/- 0.1; 100 Hz: 1.7 +/- 0.1 vs 1.4 +/- 0.2). The antinociception obtained by stimulation of acupoint St36 was only achieved when high frequency 100 Hz (3.0 +/- 0.2 vs 1.0 +/- 0.1) was used, and not with 5 or 30 Hz (1.2 +/- 0.2 and 0.7 +/- 0.1 vs 1.0 +/- 0.1). The antinociceptive effect of acupuncture occurred by opioid pathway activation, since naloxone (1 and 2 mg/kg, subcutaneously) antagonized it (1.8 +/- 0.2 and 1.7 +/- 0.2 vs 3.0 +/- 0.1).

Topics: Acupuncture Analgesia; Acupuncture Points; Animals; Electroacupuncture; Facial Pain; Male; Naloxone; Narcotic Antagonists; Pain Measurement; Pain Threshold; Rats; Rats, Wistar; Receptors, Opioid

The brain-derived interleukin-1beta (IL-1beta) has been involved in the modulation of nociceptive processing. The direction of the effects, however, analgesia or hyperalgesia, is controversial. Here, we report the role of IL-1beta injected intracisternally in orofacial pain transmission. Experiments were carried out on 90 male SD rats and surgical procedures were performed under pentobarbital sodium. Intracisternal injection of 0.3 or 0.6 microg of N-methyl-d-aspartic acid (NMDA) produced intense scratching behavioral responses including vocalization, agitation and a desire to escape in a dose-related manner. The intracisternal injection of 1 or 10 ng IL-1beta significantly decreased the NMDA-evoked scratching behavioral responses. Pretreatment with an IL-1 receptor antagonist or naloxone, an opioid receptor antagonist, blocked the IL-1beta-induced antinociceptive response. These results suggest that cytokine injected intracisternally seems to produce antinociceptive effects in the NMDA-evoked pain model of the orofacial area and the antinociceptive effect seems to be mediated by an opioid pathway.

Topics: Animals; Behavior, Animal; Cisterna Magna; Dose-Response Relationship, Drug; Facial Pain; Injections, Intraventricular; Interleukin-1; Male; N-Methylaspartate; Naloxone; Rats; Rats, Sprague-Dawley; Receptors, Interleukin-1

The aim of the present study is to clarify whether physiological stimulation of vagal afferents modulates the activity of the trigeminal spinal nucleus oralis (TSNO) neurons related to the tooth-pulp (TP)-evoked jaw-opening reflex (JOR) in pentobarbital-anesthetized rats. The activity of TSNO neurons and the amplitude of digastric electromyogram (dEMG) increased proportionally during 1.0-3.5 times the threshold for JOR. The amplitude of the dEMG of 14 out of 17 rats was suppressed by physiological stimulation of vagal afferents after intravenous infusion of Ficoll. Out of 23, 18 TSNO unit activities in 14 rats were also suppressed by Ficoll infusion. This suppressive effect of unit and dEMG activities returned to the control level within 25 min. After administration of naloxone (0.5 and 1.0 mg/kg, i.v.) the suppressive effect of Ficoll infusion on the activity of TSNO neurons (5/7) was significantly attenuated compared to the control (p < 0.01). The inhibition TSNO neuronal and dEMG activities by Ficoll infusion was volume-dependent in a range of 5-10% of total blood volume. Furthermore, right vagus nerve ligation greatly inhibited the suppressive effect of Ficoll-induced TSNO activity. These results therefore suggest that low-pressure cardiopulmonary baroreceptors whose afferents travel in the vagus nerve inhibit the pulpal nociceptive transmission.

Topics: Animals; Dental Pulp; Electric Stimulation; Electromyography; Facial Pain; Ficoll; Jaw; Ligation; Male; Naloxone; Narcotic Antagonists; Neurons, Afferent; Nociceptors; Rats; Reflex; Trigeminal Nucleus, Spinal; Vagus Nerve

The present study compared the peripheral and systemic antinociceptive effect of morphine on formalin-induced facial pain behavior in the rat. Formalin (5%, 50 microliters) was injected subcutaneously into the vibrissal pad of adult rats (250-300 g). Morphine sulfate at doses of 100-1000 micrograms was subcutaneously injected locally (same area) or systemically (in the neck), 30 min before, or simultaneously with, formalin. The typical biphasic face grooming response, consisting of an early phasic phase (0-6 min) and a delayed tonic phase (12-42 min), displayed by control animals, was suppressed by both local and systemic administration of morphine; this effect was dose dependent. However, the suppression of the early phase with local morphine administration 30 min before formalin could be significantly greater (49-52%) than with systemic administration, depending on the dose used. Administration of local morphine simultaneously with formalin produced up to 34% reduction in the early and an additional 32% reduction of the late phases of face grooming, compared to systemic injections. Local injection of naloxone (10 micrograms) almost completely reversed the antinociceptive effect of 1000 micrograms of morphine (early phase 85 +/- 7%, late phase 100 +/- 26% reduction), whereas the same dose of naloxone applied systemically (i.p.) produced only partial reversal (early phase 29 +/- 16%, late phase 36 +/- 1% reduction). This study further indicates that locally administered morphine can exert an analgesic effect superior to systemic administration in the case of inflammatory and non-inflammatory pain through a peripheral site of action. These results support the clinical use of peripheral opioid administration in the treatment of human painful conditions.

Topics: Analgesics, Opioid; Animals; Dose-Response Relationship, Drug; Facial Pain; Formaldehyde; Grooming; Injections, Subcutaneous; Male; Morphine; Naloxone; Narcotic Antagonists; Nociceptors; Rats; Rats, Sprague-Dawley; Vibrissae