piperidines and Trigeminal-Neuralgia

Topics: Arteries; Artifacts; Cerebellum; Consciousness Monitors; Craniotomy; Decompression, Surgical; Diagnostic Errors; Electromyography; Facial Nerve; Humans; Intraoperative Complications; Male; Microsurgery; Middle Aged; Monitoring, Intraoperative; Pain; Piperidines; Propofol; Prostheses and Implants; Remifentanil; Trigeminal Nerve; Trigeminal Neuralgia

This report shows a rare case of muscle rigidity by remifentanil just before the end of surgery. A 71-year-old man was scheduled for microvascular decompression to cure trigeminal neuralgia. Anesthesia was induced with propofol, suxamethonium and remifentanil 0.26 microg x kg(-1) x min(-1). Thirty minutes before the end of surgery, intratracheal pressure suddenly increased over 40 cmH2O, which was induced by muscle rigidity and the patient was difficult to be ventilated under anesthesia with sevoflurane 1% and remifentanil 0.05 microg x kg(-1) x min(-1). After giving muscle relaxants, the patient was uneventful. We should pay attention to muscle rigidity even using low doses of remifentanil.

Topics: Aged; Anesthesia; Anesthetics, Intravenous; Decompression, Surgical; Humans; Intraoperative Complications; Male; Muscle Rigidity; Piperidines; Remifentanil; Respiration Disorders; Respiratory Muscles; Trigeminal Neuralgia

The susceptibility of changes in responsiveness to noxious cold stimulation of rats submitted to chronic constriction of the infraorbital nerve (CION) or carrageenan to drug inhibition was compared. Nocifensive responses were measured as total time rats engaged in bilateral facial grooming with both forepaws over the first 2 min following tetrafluoroethane spray application to the snout. Carrageenan (50 microg, s.c. into upper lip) caused short-lived ipsilateral cold hyperalgesia (peak at 3 h: vehicle 8.4+/-1.3, carrageenan 21.2+/-3.0 s) which was markedly suppressed by i.p. indomethacin (4 mg/kg), celecoxib (10mg/kg) or s.c. dexamethasone (0.5 mg/kg), endothelin ET(A) or ET(B) receptor antagonists (BQ-123 and BQ-788, respectively; 10 nmol/lip). CION caused ipsilateral cold hyperalgesia between Days 2 and 12, which peaked on Days 4 (sham 15.3+/-1.8, CION 32.4+/-5.3s) to 6. Established peak CION-induced cold hyperalgesia was unaffected by indomethacin and celecoxib, whereas dexamethasone, BQ-123, BQ-788, and i.v. injections of selective antagonists of ET(A) (atrasentan, 3-10 mg/kg) or ET(B) (A-192621, 5-20 mg/kg) receptors caused significant inhibitions lasting 1-2.5h (peaks approximately 65-90%). Bosentan (dual ET(A)/ET(B) receptor antagonist, 10 mg/kg, i.v.) abolished CION-induced cold hyperalgesia for up to 6h. Thus, once established, CION-induced orofacial hyperalgesia to cold stimuli appears to lack an inflammatory component, but is alleviated by endothelin ET(A) and/or ET(B) receptor antagonists. If this CION injury model bears predictive value to trigeminal neuralgia (i.e., paroxysmal orofacial pain triggered by various stimuli), endothelin receptors might constitute new targets for treatment of this disorder.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Atrasentan; Bosentan; Carrageenan; Celecoxib; Cold Temperature; Dexamethasone; Disease Models, Animal; Drug Evaluation, Preclinical; Endothelin-1; Endothelins; Grooming; Hyperalgesia; Indomethacin; Male; Maxillary Nerve; Nerve Compression Syndromes; Oligopeptides; Peptide Fragments; Peptides, Cyclic; Piperidines; Pyrazoles; Pyrrolidines; Rats; Rats, Wistar; Receptor, Endothelin A; Receptor, Endothelin B; Sulfonamides; Trigeminal Neuralgia

F 13640 is a recently discovered high-efficacy 5-HT1A receptor agonist that has demonstrated robust anti-allodynic efficacy in a rat model of trigeminal neuropathic pain upon acute and continuous administration. In this model, continuous morphine infusion (5 mg/day) was shown to be effective during the first week of its administration but became almost completely ineffective by the end of the second week; F 13640's effectiveness (0.63 mg/day) remained unchanged during two weeks. Here, we examined the effects of combining F 13640 infusion with that of morphine. During the first week, the combination of the two agents produced a magnitude of effect that was similar to that of morphine when given alone and larger than that of F 13640 alone. During the second week, the combination produced an effect that was similar to that of F 13640 alone, and more effective than that of morphine alone. The latter data suggest that the 5-HT1A agonist, F 13640, inhibits the development of tolerance to morphine in this model. However, it is also possible that little, if any, interaction occurred between the different mechanisms initiated by opioid and 5-HT1A receptor activation, and that the anti-allodynic effect that remained by the end of the two-week treatment period is due solely to 5-HT1A receptor activation. The stable effects of F 13640 during the second week of treatment surpassed those of morphine and were not improved by the addition of morphine to F 13640.

Topics: Aminopyridines; Analgesics, Opioid; Animals; Behavior, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Drug Tolerance; Infusion Pumps, Implantable; Male; Morphine; Pain Measurement; Physical Stimulation; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT1A; Serotonin Receptor Agonists; Trigeminal Neuralgia

(3-Chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl]piperidin-1-yl]-methadone (F 13640) is a recently discovered high-efficacy 5-hydroxytryptamine (HT)1A receptor agonist that produces central analgesia through the neuroadaptive mechanisms of inverse tolerance and cooperation. In a rat model of trigeminal neuropathic pain, the chronic constriction injury of the infraorbital nerve causes allodynia-like behavior that develops within 2 weeks and remains stable thereafter. We report that early after surgery, during which time allodynia develops, the continuous 2-week infusion of 0.63 mg/day F 13640 inhibited the allodynia-like behavior, whereas 5 mg/day morphine showed no significant effect. When F 13640 infusion was initiated late after surgery, when allodynia was well established, it produced an antiallodynic effect that was apparent during the entire infusion period. In contrast, morphine infusion caused an initially marked antiallodynic effect to which tolerance developed within the 2-week infusion period. The GABA-B receptor agonist baclofen (1.06 mg/day) that has a recognized usefulness in the treatment of trigeminal neuralgia, demonstrated effectiveness in both conditions. The data are consistent with a theory of nociceptive signal transduction, as well as with previous data, in demonstrating the neuroadaptive mechanisms of inverse tolerance and cooperation. That is, in contrast with morphine, the antiallodynic effect induced by 5-HT1A receptor activation does not decay, but, if anything, grows with chronicity. Also, 5-HT1A receptor activation seemed to cooperate with nociceptive stimulation in, paradoxically, inducing an antiallodynic effect. The data presented here suggest that F 13640 may perhaps offer a lasting treatment of trigeminal neuralgia.

Topics: Analgesics, Opioid; Analysis of Variance; Animals; Behavior, Animal; Disease Models, Animal; Male; Pain; Pain Measurement; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Trigeminal Neuralgia

The effects of acute intraperitoneal injections of the 5-HT(1A) receptor agonists F 13640 [(3-chloro-4-fluoro-phenyl)-[4-fluoro-4-[[(5-methyl-pyridin-2-ylmethyl)-amino]-methyl]piperidin-1-yl]-methadone] and F 13714 [3-chloro-4-fluorophenyl-(4-fluoro-4-[[(5-methyl-6-methylamino-pyridin-2-ylmethyl)-amino]-methyl]-piperidin-1-yl-methanone] were studied in comparison with those of baclofen and morphine on responsiveness to von Frey hair stimulation after chronic constriction injury to the rat's infraorbital nerve (IoN-CCI). Following IoN-CCI, an ipsilateral hyperresponsiveness developed that remained stable in control rats throughout the period of drug testing. F 13640, F 13714, baclofen and morphine dose-dependently decreased the hyperresponsiveness; normalization of the response occurred at doses 0.63, 0.04, 5 and 10 mg/kg, respectively. Confirming earlier data, baclofen's effects further validate IoN-CCI as a model of trigeminal neuralgia. The effects of F 13640 and F 13714 are initial evidence that 5-HT(1A) receptor agonists produce profound analgesia in the IoN-CCI model. The present data extend recent evidence that high-efficacy 5-HT(1A) receptor activation constitutes a new mechanism of central analgesia the spectrum of which may also encompass trigeminal neuropathic pain.

Topics: Aminopyridines; Animals; Baclofen; Behavior, Animal; Disease Models, Animal; Dose-Response Relationship, Drug; Male; Morphine; Muscle Relaxants, Central; Narcotics; Pain; Piperidines; Pyridines; Rats; Rats, Sprague-Dawley; Receptors, Serotonin; Receptors, Serotonin, 5-HT1; Serotonin Receptor Agonists; Stress, Mechanical; Trigeminal Neuralgia