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GABAA Receptors

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Abstract:

GABA Receptors Modulate Trigeminovascular Nociceptive Neurotransmission in the Trigeminocervical Complex

Storer RJ, Akerman S, Goadsby PJ

Br J Pharmacol 2001;134:896–904

METHODS: GABA (gamma-aminobutyric acid) receptors involved in craniovascular nociceptive pathways were characterised by in vivo microiontophoresis of GABA receptor agonists and antagonists onto neurones in the trigeminocervical complex of the cat. Extracellular recordings were made from neurons in the trigeminocervical complex activated by supramaximal electrical stimulation of superior sagittal sinus, which were subsequently stimulated with L-glutamate.

RESULTS: Cell firing evoked by microiontophoretic application of L-glutamate (n = 30) was reversibly inhibited by GABA in every cell tested (n = 19), the GABA(A) agonist muscimol (n = 10) in all cells tested, or both where tested, but not by iontophoresis of either sodium or chloride ions at comparable ejection currents. Inhibited cells received wide dynamic range (WDR) or nociceptive specific input from cutaneous receptive fields on the face or forepaws. The inhibition of trigeminal neurons by GABA or muscimol could be antagonized by the GABA(A) antagonist N-methylbicuculline, 1(S), 9(R) in all but two cells tested (n = 16), but not by the GABA(B) antagonist 2-hydroxysaclofen (n = 11). 5. R(-)-baclofen, a GABA(B) agonist, inhibited the firing of three out of seven cells activated by L-glutamate. Where tested, this inhibition could be antagonized by 2-hydroxysaclofen. These baclofen-inhibited cells were characterized as having low threshold mechanoreceptor/WDR input.

CONCLUSION: GABA thus appears to modulate nociceptive input to the trigeminocervical complex mainly through GABA(A) receptors. GABA(A) receptors may therefore provide a target for the development of new therapeutic agents for primary headache disorders.

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1743-5013.2004.10102E.x

Publication date: July 1, 2004

bsc/hec/2004/00000001/00000001/art00011
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