dizocilpine-maleate and Facial-Pain

The NMDA receptor plays a large role in opioid-induced plastic changes in the nervous system. The expression levels of its NR1 subunit are altered dramatically by morphine but no changes in its alternative splicing have been reported. Changes in the splicing of the N1, C1, C2, and C2' cassettes can alter the pharmacology and regulation of this receptor. Western Blots run on brain tissue from rats made tolerant to morphine revealed altered splicing of the N1 cassettes in the accumbens and amygdala (AMY), and the C1 cassette in the AMY and the dorsal hippocampus (HIPP). After 3days of withdrawal C2'-containing NR1 subunits were down-regulated in each of these areas. These were not due to acute doses of morphine and may represent long-term alterations in drug-induced neuroplasticity. We also examined the effects of morphine tolerance on an operant orofacial nociception assay which forces an animal to endure an aversive heat stimulus in order to receive a sweet milk reward. Morphine decreased pain sensitivity as expected but also increased motivational reward seeking in this task. NMDAR antagonism potentiated this reward seeking behavior suggesting that instead of attenuating tolerance, MK-801 may actually alter the rewarding and/or motivational properties of morphine. When combined, MK-801 and morphine had an additive effect which led to altered splicing in the accumbens, AMY, and the HIPP. In conclusion, NR1 splicing may play a major role in the cognitive behavioral aspects especially in motivational reward-seeking behaviors.

Topics: Alternative Splicing; Animals; Conditioning, Operant; Dizocilpine Maleate; Drug Therapy, Combination; Facial Pain; Male; Morphine; Motivation; Nociception; Rats; Rats, Hairless; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Reward

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

We have previously documented that peripheral N-methyl-d-aspartate (NMDA) receptor mechanisms are involved in nociceptive reflex increases in jaw muscle activity to injection of mustard oil or glutamate into the rat temporomandibular joint (TMJ). The aim of the present study was to determine whether peripheral NMDA receptor mechanisms are also involved in the nociceptive reflex responses in the jaw muscles evoked by injection of the inflammatory irritant and algesic chemical capsaicin into the TMJ. The effects of peripheral injection of NMDA receptor antagonists, MK-801 and APV, on the increases in electromyographic (EMG) activities of digastric and masseter muscles reflexly evoked by capsaicin injection into the TMJ were tested in halothane-anesthetized male rats. The capsaicin injection following pre-injection of vehicle evoked significant increases in EMG activity in both digastric and masseter muscles whereas pre-injection of MK-801 or APV into the TMJ resulted in a significant concentration-related reduction in the magnitude of capsaicin-evoked digastric and masseter EMG activity (ANOVA-on-ranks, P < 0.05). This finding indicates that capsaicin-evoked digastric and masseter EMG activity can be attenuated by pre-injection into the TMJ of NMDA receptor antagonists, and that the activation of peripheral NMDA receptors may be important in the mechanisms whereby capsaicin evokes nociceptive trigeminal responses.

Topics: Analysis of Variance; Animals; Capsaicin; Disease Models, Animal; Dizocilpine Maleate; Electromyography; Excitatory Amino Acid Antagonists; Facial Pain; Inflammation; Jaw; Male; Muscle, Skeletal; Nociceptors; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Reflex; Temporomandibular Joint; Valine