piperidines and Pain--Intractable

The midbrain periaqueductal grey (PAG) is a structure known for its roles in pain transmission and modulation. Noxious stimuli potentiate the glutamate synaptic transmission and enhance glutamate NMDA receptor expression in the PAG. However, little is known about roles of NMDA receptor subunits in the PAG in processing the persistent inflammatory pain. The present study was undertaken to investigate NR2A- and NR2B-containing NMDA receptors in the PAG and their modulation to the peripheral painful inflammation. Noxious stimuli induced by hind-paw injection of complete Freund's adjuvant (CFA) caused up-regulation of NR2B-containing NMDA receptors in the PAG, while NR2A-containing NMDA receptors were not altered. Whole-cell patch-clamp recordings revealed that NMDA receptor mediated mEPSCs were increased significantly in the PAG synapse during the chronic phases of inflammatory pain in mice. PAG local infusion of Ro 25-6981, an NR2B antagonist, notably prolonged the paw withdrawal latency to thermal radian heat stimuli bilaterally in rats. Hyperoside (Hyp), one of the flavonoids compound isolated from Rhododendron ponticum L., significantly reversed up-regulation of NR2B-containing NMDA receptors in the PAG and exhibited analgesic activities against persistent inflammatory stimuli in mice. Our findings provide strong evidence that up-regulation of NR2B-containing NMDA receptors in the PAG involves in the modulation to the peripheral persistent inflammatory pain.

Topics: Afferent Pathways; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Disease Models, Animal; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Freund's Adjuvant; Glutamic Acid; Inflammation; Male; Mice; Mice, Inbred C57BL; Nociceptors; Organ Culture Techniques; Pain Measurement; Pain, Intractable; Patch-Clamp Techniques; Periaqueductal Gray; Phenols; Piperidines; Quercetin; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Up-Regulation

To review the efficacy of naratriptan as preventive treatment in 27 patients with chronic migraine refractory to other commonly used preventive therapies.. The treatment of chronic migraine often poses a major challenge to the clinician. Even when given expert care, patients with chronic migraine may continue to have daily or near-daily headaches.. Clinical records and headache calendars were reviewed of 27 patients fulfilling the following inclusion criteria: (1) aged 18 to 65 years; (2) diagnosis of chronic migraine (formerly transformed migraine), according to the criteria proposed by Silberstein et al; (3) previous failure of at least 4 preventive medications prescribed as part of a management program that included nonpharmacological measures, preventive medication, acute care medication, and detoxification from overused medication; and (4) have used daily naratriptan for no less than 2 consecutive months. The dose of naratriptan prescribed was 2.5 mg twice daily. We considered the following outcomes: (1) frequency of headache, (2) intensity of pain, (3) number of days per month with severe headache, (4) headache index (frequency times intensity), and (5) proportion of patients who reverted to an episodic pattern of pain after 6 months of treatment.. There was a statistically significant reduction in the frequency of headache days 2 months (15.3 days versus 24.1 days at baseline, P<.001), 6 months (9.1 days, P<.001), and 1 year (7.3 days, P<.001) after daily treatment with naratriptan was initiated. There was also a statistically significant reduction in the number of days per month of severe pain at 1 month (5.6 days versus 12.5 days at baseline, P<.01), 2 months (5.7 days, P<.01), 6 months (2.8 days, P<.01), and 1 year (2.6 days, P<.01). Similarly, there was a statistically significant reduction in the headache index at 2 months (33 versus 56.4 at baseline, P<.001), 6 months (19.5, P<.001), and 1 year (17.2, P<.001). Of the 20 patients who continued to use naratriptan daily for at least 6 months, 13 (65%) reverted to an episodic pattern of pain (migraine). At 1 year, 11 (55%) still continued to experience episodic headache, 1 (5%) relapsed to chronic migraine, and 2 (10%) were lost to follow-up. No patients had intolerability to naratriptan during the treatment period, and no one stopped treatment due to adverse events.. Naratriptan may have a role in the preventive treatment of intractable chronic migraine. Prospective, controlled studies should be considered.

Topics: Adolescent; Adult; Female; Humans; Indoles; Male; Middle Aged; Migraine Disorders; Pain, Intractable; Piperidines; Retrospective Studies; Serotonin Receptor Agonists; Tryptamines

Topics: Analgesics; Anesthetics, Local; Humans; Hypnotics and Sedatives; Morphine Derivatives; Neoplasms; Neurosurgery; Pain, Intractable; Palliative Care; Piperidines; Propylamines