Oral gabapentin for scalp pruritus in patients with lichen planopilaris: A case series

Gabapentin (1-(aminomethyl)cyclohexane acetic acid; Neurontin) is a novel anticonvulsant drug, with a mechanism of action apparently dissimilar to that of other antiepileptic agents. We report here the isolation and characterization of a [3H]gabapentin-binding protein from pig cerebral cortex membranes. The detergent-solubilized binding protein was purified 1022-fold, in a six-step column-chromatographic procedure, with a yield of 3.9%. The purified protein had an apparent subunit Mr of 130,000, and was heavily glycosylated. The partial N-terminal amino acid sequence of the Mr 130,000 polypeptide, EPFPSAVTIK, was identical to that reported for the alpha2delta subunit of the L-type Ca2+ channel from rabbit skeletal muscle (Hamilton, S. L., Hawkes, M. J., Brush, K., Cook, R., Chang, R. J., and Smilowitz, H. M. (1989) Biochemistry 28, 7820-7828). High levels of [3H]gabapentin binding sites were found in membranes prepared from rat brain, heart and skeletal muscle. Binding of [3H]gabapentin to COS-7 cells transfected with alpha2delta cDNA was elevated >10-fold over controls, consistent with the expression of alpha2 delta protein, as measured by Western blotting. Finally, purified L-type Ca2+ channel complexes were fractionated, under dissociating conditions, on an ion-exchange column; [3H]gabapentin binding activity closely followed the elution of the alpha2 delta subunit. [3H]Gabapentin is the first pharmacological agent described that interacts with an alpha2delta subunit of a voltage-dependent Ca2+ channel. Show more

Gabapentin and pregabalin are amino acid derivatives of gamma-amino butyric acid that have anticonvulsant, analgesic, and anxiolytic-like properties in animal models. The mechanisms of these effects, however, are not well understood. To ascertain whether these drugs have effects on sensory neurons, we studied their actions on capsaicin-evoked release of the sensory neuropeptides, substance P and calcitonin gene-related peptide from rat spinal cord slices in vitro. Although release of immunoreactive peptides from non-inflamed animals was not altered by either drug, prior in vivo treatment by intraplantar injection of complete Freund's adjuvant enhanced release from spinal tissues in vitro, which was attenuated by gabapentin and pregabalin. These drugs also reduced release of immunoreactive neuropeptides in spinal tissues pretreated in vitro with the protein kinase C activator, phorbol 12,13-dibutyrate. Our results suggest that gabapentin and pregabalin modulate the release of sensory neuropeptides, but only under conditions corresponding to significant inflammation-induced sensitization of the spinal cord. Show more

Lichen planopilaris (LPP) is the prototype of scarring alopecias that mainly target the infundibuloisthmic (bulge) region of hair follicle. Hair follicle stem cells have been shown to reside in the bulge. We carried out this study to better define the possible pathogenetic role of the bulge in LPP. Thirty-five cases of LPP were studied. Multiple serial sections of biopsy specimens stained with hematoxylin and eosin, periodic acid Schiff-diastase, and Elastic van Gieson. The following immunostains were applied: CD3, CD4, CD8, CD1a, and Ki-67. Uninvolved follicles and normal scalp biopsy specimens served as normal controls. All cases showed a lichenoid lymphocytic infiltrate at the bulge region. The bulb area was spared. CD8(+) T cells were increased compared with CD4(+) T-cell population. Langerhans' cells were decreased. Proliferating stem cells, highlighted by Ki-67, showed a marked decrease in the bulge compared with uninvolved follicles. Our study supports the finding that in LPP, the inflammatory infiltrate mainly involves the bulge region, where the stem cells reside. Once this area is damaged, the hair loses its potential of regrowth with resulting scarring alopecia. This is in contrast with inflammatory non-scarring alopecias such as alopecia areata, where the bulb region is targeted, sparing the stem cells. Show more