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- Title
HEADACHE PATHOPHYSIOLOGY AND BASIC SCIENCE.
- Authors
Millson, David S.; Tepper, Stewart J.
- Abstract
Paternain AV, Cohen A, Stern-Bach Y, Lerma J. A role for extracellular Na+ in the channel gating of native and recombinant kainate receptors. J Neurosci. 2003;24:8641-8648. Ionotropic glutamate receptors of the kainate and AMPA subtypes share a number of structural features, both topographical and in terms of stoichiometry. In addition, AMPA and kainate receptors share similar pharmacological and biophysical properties in that they are activated by common agonists and display rapid activation and desensitization characteristics. However, we show here that in contrast to AMPA receptor-mediated responses (native or recombinant GluR3 receptor), the response of native and recombinant (GluR6) kainate receptors to glutamate was drastically reduced in the absence of extracellular Na+ (i.e., when replaced by Cs+). Removal of Na+ increases the rate of desensitization, indicating that external Na+ modulates channel gating. Whereas the size of the substituting cation is important in mimicking the action of Na+ (Li+>K+>Cs+), modulation was voltage independent. These results indicate the existence of different gating mechanisms for AMPA and kainate receptors. By using chimeric AMPA-kainate receptors derived from GluR3 and GluR6, we have identified a key residue in the S2 segment of GluR6 (M770) that is largely responsible for the sensitivity of the receptor to external Na+. Thus, these results show the existence of a specific kainate receptor gating mechanism that requires external Na+ to be operative. Comments: Given that at least one form of familial hemiplegic migraine is associated with an abnormality in sodium channels, and that at least one glutamate AMPA (amino-3-hydroxy-5-methylisoxazole-4-propionic acid)-kainate receptor antagonist has been found to be effective in aborting migraine (Sang CM, Ramadan NM, Chappell AS, et al. A double-blind, placebo-controlled study to investigate the efficacy and tolerability of intravenous 1.2 mg/kg LY293558 vs. 6 mg subcutaneous sumatriptan vs. placebo in patients with an acute migraine attack [abstract]. Neurology. 2001;56(suppl 3):A219), it behooves us to try to stay up to date on the characteristics of glutamate receptors, their characteristics, and their relationship to sodium and other ion channels. SJT Valeriani M, de Tommaso M, Restuccia D, Le Pera D, Guido M, Iannetti GD, Libro G, Truini A, Di Trapani G, Puca F, Tonali P, Cruccu G. Reduced habituation to experimental pain in migraine patients: a CO(2) laser evoked potential study. Pain. 2003;105:57-64. The habituation to sensory stimuli of different modalities is reduced in migraine patients. However, the habituation to pain has never been evaluated. Our aim was to assess the nociceptive pathway function and the habituation to experimental pain in patients with migraine. Scalp potentials were evoked by CO(2) laser stimulation (laser evoked potentials, LEPs) of the hand and facial skin in 24 patients with migraine without aura (MO), 19 patients with chronic tension-type headache (CTTH), and 28 control subjects (CS). The habituation was studied by measuring the changes of LEP amplitudes across three consecutive repetitions of 30 trials each (the repetitions lasted 5 min and were separated by 5-min intervals). The slope of the regression line between LEP amplitude and number of repetitions was taken as an index of habituation. The LEPs consisted of middle-latency, low-amplitude responses (N1, contralateral temporal region, and P1, frontal region) followed by a late, high-amplitude, negative-positive complex (N2/P2, vertex). The latency and amplitude of these responses were similar in both patients and controls. While CS and CTTH patients showed a significant habituation of the N2/P2 response, in MO patients this LEP component did not develop any habituation at all after face stimulation and showed a significantly lower habituation than in CS after hand stimulation. The habituation index of the vertex N2/P2 complex exceeded the normal limits in 13 out of the 24 MO patients and in none of the 19 CTTH patients ( P < 0.0001; Fisher's exact test). Moreover, while the N1-P1 amplitude showed a significant habituation in CS after hand stimulation, it did not change across repetitions in MO patients. In conclusion, no functional impairment of the nociceptive pathways, including the trigeminal pathways, was found in either MO or CTTH patients. But patients with migraine had a reduced habituation, which probably reflects an abnormal excitability of the cortical areas involved in pain processing. Comment: An interesting study, further evidence of neuronal hyperexcitability in migraine brain. SJT
- Subjects
HEADACHE; PATHOLOGICAL physiology; SODIUM channels; PAIN; MIGRAINE
- Publication
Headache: The Journal of Head & Face Pain, 2004, Vol 44, Issue 3, p299
- ISSN
0017-8748
- Publication type
Abstract
- DOI
10.1111/j.1526-4610.2004.t01-8-04068.x