title: Induction of corneal lesion and nerve fiber sprouting by neonatal capsaicin application depends on the dose of the drug and survival time after treatment.
abstract: The effects of capsaicin on the rat cornea and its NsAchE (non specific acetylcholinesterase)-positive nerve fibers were investigated after long and short survival periods following subcutaneous (s.c) injection of the drug. Sixteen rats were injected once s.c with capsaicin on postnatal day 2 at a dose of 50 mg/kg. Age-matched rats were injected only vehicle, and served as control (n = 16). After 4 (n = 6), 8 (n = 6) and 12 (n = 4) mos., both sides of the corneas were examined under a binocular microscope to look for corneal abnormalities. Immediately after the enucleation, bilateral corneas were excised with a thin scleral margin and their ciliary body and iris were removed in DPBS solution. Then, they were fixed in a 4% paraformaldehyde solution containing 8% sucrose for 1 h at 4 degrees C, and processed for staining by the NsAchE method. For comparison, 15 rats were injected 3 times with capsaicin (total dose: 150 mg/kg) at a dose of 50 mg/kg on days 1, 2 and 3 after birth. Age-matched rats (n = 16) were injected vehicle as controls. Five (n = 4), 17 (n = 4), 45 (n = 3) and 75 (n = 4) days later, their corneas were similarly handled as described above. Corneal lesions and sprouting of the NsAchE-positive subepithelial nerve fibers appeared 4 mos. after the treatment with capsaicin (50 mg/kg). In particular, all the treated corneas (8/8) at 12 mos. showed corneal abnormalities. Contrary to the results from the single injection of capsaicin, corneal changes had already appeared on day 17 after treatment with capsaicin at a high dose (150 mg/kg). These data reinforce the suggestion that yielding of corneal lesions is closely associated with the longer survival time at lower doses and with the short survival time at a high dose of the drug. Further, the relationship between sprouting of corneal nerve fibers and corneal wounds was discussed on the basis of the previous reports.
authors.affiliation: Department of 2nd Oral Anatomy, School of Dentistry, University of Tokushima. hiuraaki@dent.tokushima-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Hiura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D009412:Nerve Fibers / Q000187:drug effects* / Q000473:pathology; D051381:Rats
chemical_list: D002211:Capsaicin