Abstract
Purpose: :
To evaluate the effect of different sodium channel blockers on the electrical activity of corneal sensory nerves recorded from intact and injured corneas.
Methods: :
In anesthetized guinea-pigs, a 4mm-diameter corneal flap was cut in one eye at mid-stromal depth using a custom-made microkeratome. At 3-5 days after surgery, the whole eye or the isolated cornea were mounted in a superfused recording chamber. Electrical activity of corneal sensory receptors was recorded from nerve filaments dissected from the ciliary nerves (NF) or from corneal nerve terminals (CNT). Thermal stimulation was performed changing the temperature of the perfusion solution from 32ºC down to 20°C or up to 50ºC. Mechanical stimulation was applied using calibrated von Frey hairs (NF recordings) or applying pressure with the pipette electrode (CNT recordings). Chemical stimulation was tested applying for 30s a 98% CO2 gas pulse. The characteristics of the spontaneous (SA) and stimulus-evoked activity were analyzed in sensory receptors recorded from intact (n=355 NF, 104 CNT) and lesioned (n=152 NF, 56 CNT) corneas, before and after treatment with several drugs that act as sodium channel blockers (lidocaine, carbamazepine, phenytoin, amitriptyline, lamotrigine and gabapentine) at different concentrations.
Results: :
Compared to intact corneas, injured corneas showed higher cold CNT spontaneous activity at basal temperature, and lower threshold and enhanced discharge rate in response to cooling. In intact and lesioned corneas, the tested drugs reduced in a dose-dependent manner both, SA and cold-evoked activity of cold CNT. Mechano and polymodal (PN) nociceptors recorded from NF showed transitory increase of SA and enhanced responses to mechanical and chemical stimuli. Mechanical threshold was not affected by sodium channel blockers, while the response of PN to CO2 in intact and lesioned corneas was significantly reduced by these drugs, being carbamazepine the most effective one.
Conclusions: :
The increased activity observed in injured cold-sensitive nerve terminals, and the transient increase in spontaneous and evoked activity observed in injured polymodal nociceptors seem to be due to an enhanced expression of tetrodotoxin-resistant sodium channels. Therefore, Na+-channel blockers may be potential tools to attenuate abnormal activity in regenerating nerves thus reducing spontaneous pain and allodynia that often follow corneal lesions.
Keywords: innervation: sensation • receptors: pharmacology/physiology • lesion study