Abstract
Purpose :
Latent sensitization (LS) is a silent state of neuronal sensitization controlled by the constitutive activity of endogenous opioid receptors. It is known to modulate pain perception, however, its role in ocular pain has not been established. In this study, we developed a clinically relevant experimental model that displays features of ocular neuropathic pain and established the role of LS.
Methods :
Ocular surface injury was induced in C57BL/6 mice by alkali injury (0.75N NaOH; pH 13.0±0.05) at the center of the right cornea for 10 seconds. Before (baseline) and at days 2, 4, 7, 10, 21, and 42 after injury, eye-wiping was counted for 30 seconds after instillation of hypertonic saline solution (2M NaCl; pH 7.4±0.05) to the eye surface, compared to sham treated mice. At 7 weeks post injury, naltrexone (NTX), an inverse agonist of mu-opioid receptor (MOR), was subcutaneously administered (3mg/kg). After 30 minutes, the eye-wiping test was performed.
Results :
At baseline, there was no significant difference in the number of eye wipes between sham group (11.6±1.3) (mean ± SEM) and injury group (11.8±1.5). On day 10, the injury group (19.4±3.3) increased eye wipes by 64.4% compared to the baseline level (p<0.01) while the sham group (11.3±2.3) did not increase, resulting in a significant difference in eye-wiping behavior between groups (p<0.05). After the peak, eye wipes in the injury group (12.2±2.8) declined and returned to the baseline level at 42 days post injury while the number of eye wipes in the sham group (11.4±2.9) remained at baseline levels, showing no significant difference between groups. At 7 weeks post injury, administration of NTX increased eye wipes in the injury group (19.2±2.4) by 54.8% (p<0.05), but not in the sham group (13.4±2.0), with a significant difference in eye-wiping behavior between groups (p<0.05).
Conclusions :
Our model of ocular neuropathic pain accompanies the constitutive activity of MOR (MORCA)-dependent LS, which could be a potential diagnostic and therapeutic target to prevent the transition from acute to chronic pain or to alleviate enhanced sensitivity in the chronic pain state. This model will be used to study the underlying neurobiology and pathophysiology, ultimately elucidating ways to avoid LS or enhance the MORCA in the ocular trigeminal system.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.