Dorsal root ganglion neurons show increased expression of the calcium channel alpha2delta-1 subunit following partial sciatic nerve injury.

Neuropathic pain is associated with changes in the electrophysiological and neurochemical properties of injured primary afferent neurons. A mRNA differential display study in rat L(4/5) dorsal root ganglia (DRGs) revealed upregulation of the calcium channel alpha2delta-1 subunit 2 weeks after partial sciatic nerve ligation (Seltzer model of neuropathic pain). The upregulated transcript appeared to represent previously unidentified sequence from the 3'-untranslated region of rat alpha2delta-1 mRNA. In situ hybridization using L(5) DRGs from sham operated rats showed that 73, 40 and 19% of small (<700 microm(2)), medium (700-1100 microm(2)) and large (>1100 microm(2)) neuronal profiles, respectively, expressed alpha2delta-1 mRNA. Two weeks following nerve injury there was a significant ipsilateral increase, both in the percentage of DRG neurons expressing alpha2delta-1 mRNA and in the intensity of the hybridization signal. Comparison of this ipsilateral expression with that in sham animals, revealed that for small, medium and large neurons, respectively, the proportion of neurons labelled increased by 1.2-, 1.8- and 2.7-fold, while the hybridization signal in alpha2delta-1-labelled neurons increased by 2.8-, 2.5- and 3.7-fold. The most intensely labelled neuronal profiles in ipsilateral, sham and contralateral DRGs, were generally those with small cross-sectional areas. The alpha2delta-1 auxiliary subunit is known to modulate calcium channel function in heterologous expression systems via its association with the pore-forming alpha1 calcium channel subunit. Therefore the increased levels of this subunit in the populations of primary afferents described may, via modulation of calcium-dependent processes such as neurotransmitter release and neuronal excitability, influence the processing of sensory information.

Methotrexate and etretinate as concurrent therapies in severe psoriasis.

A patient with pustular psoriasis, which was inadequately controlled by high-dose methotrexate and potent topical corticosteroid therapy, was treated with oral methotrexate and the aromatic retinoid etretinate. The patient's psoriasis improved with sustained maximal etretinate therapy and continued high-dose methotrexate therapy. Subsequently, the methotrexate dose was tapered and used of this drug was discontinued. Previously unattainable success in controlling the psoriasis was achieved with continued etretinate treatment. There were no recognizable adverse effects from concurrent therapy. As the methotrexate dose was tapered, the patient noted increased psoriatic arthritic pain, unrelieved at maximal etretinate levels, but improved with indomethacin treatment. Combination therapy with methotrexate and etretinate may be useful in the treatment of severe psoriasis by providing a controlled transition from methotrexate to etretinate therapy alone.

Topical therapy of alopecia areata with squaric acid dibutylester.

The efficacy of the topical allergen squaric acid dibutylester (SADBE) was investigated in the treatment of twenty-six patients with alopecia areata or alopecia totalis. The patients had their disease for a mean duration of 8.3 years (range, 3 months to 27 years). Sensitization was attempted with 2% SADBE in acetone. Five individuals could not be sensitized. The twenty-one sensitized patients were treated with topical applications of 0.001% to 1.0% SADBE in acetone adjusted to produce and maintain dermatitis for an average of 21 weeks. Eleven (52%) had excellent responses consisting of complete regrowth in six and cosmetically acceptable regrowth in five. The average treatment time for regrowth was 11 weeks (range, 5-20 weeks). Ten (48%) had no clinical response after an average of 19 weeks of therapy (range, 4-42 weeks). Topical SADBE is an effective therapy for some patients with long-standing alopecia areata.