Diltiazem spares corneal A delta mechano and C fiber cold receptors and preserves epithelial wound healing.
Recent interest in the corneal analgesic properties of diltiazem prompted the present study examining concentration-dependent effects of this calcium channel blocker on C fiber cold receptors and A delta mechanoreceptors. Both afferent fiber types mediate an eye blink reflex, important for protecting the corneal surface. The effects of neuroactive concentrations of diltiazem on corneal would healing were also studied. An in vitro rabbit cornea preparation was used for both electrophysiological recording and wound healing, allowing precise concentration-response analysis. Diltiazem produced a concentration-dependent depression of cold fiber discharge activity (10 to 250 microM), but did not affect mechanoreceptor afferents. In addition, the broad spectrum Ca2+ channel blockers, Ni2+ and Cd2+, did not cause a significant reduction in A delta mechano or C fiber discharge activity. Diltiazem had no effect on corneal epithelial wound healing to a concentration of 50 microM. This is important if diltiazem is to be used for therapeutic control of pain following corneal injury or surgery, because sparing of the eye blink reflexes and wound healing are desirable properties for a corneal analgesic.
Pain Research Laboratory, Stanford University School of Medicine, California 94305-5117, USA.
A A
AA
Mikulec
H S
HS
Lukatch
F A
FA
Monroe
M B
MB
MacIver
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003315:Cornea / Q000187:drug effects / Q000294:innervation*; D004110:Diltiazem / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004848:Epithelium / Q000187:drug effects / Q000294:innervation; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D009412:Nerve Fibers / Q000187:drug effects*; D009532:Nickel / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D014945:Wound Healing / Q000187:drug effects*
D002121:Calcium Channel Blockers; D002104:Cadmium; D009532:Nickel; D004110:Diltiazem