Purchase this article with an account.
Romulo Albuquerque, Jooyoung Cho, Nicholas Bell, Gregory Botzet, Paras Vora, Taylor Brad; Peripheral Latent Sensitization Masks Chronic Ocular Pain. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3273.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Significant tissue injury results in chronic sensitization of peripheral and central nerves. Pain remission occurs via constitutive activation of mu-opioid receptor (MORCA) in a process called latent sensitization (LS). This process is well established in central nervous system circuitry (spinal cord), but little is known about its peripheral components. We have established that LS modulates injury induced chronic ocular pain. In this study, we show that peripheral latent sensitization modulates chronic eye pain in mice.
Ocular surface injury and sham injury was induced in C57BL/6 mice by application of alkali solution (0.75N NaOH; pH 13.0 0.05) or BSS at the center of the cornea. At baseline and at days 10 and 28 post injury, eye-wiping was counted after instillation of hypertonic saline (2M NaCl; pH 7.4 0.05) to the eye surface. At 10 and 16 weeks post injury, the MOR inverse agonists naltrexone (NTX) and naloxone methiodide (NLX-me) (peripherally acting), were administered subcutaneously (3mg/kg) and topically (100mM) respectively. After 30 minutes and 50 minutes, the eye-wiping test was performed.
At baseline there was no difference in the number of eye wipes between sham group (10.8 ± 1.4) (mean ± SEM) and injury group (10.5 ± 1.5). On day 10, eye wiping increased (16 ± 1.8) compared to baseline (p<0.01) and sham group (9.6 ± 1.0) (p<0.05). Eye wipes in the injury group declined to the baseline at 28 days post injury similar to the sham group (10.1 ± 0.7 versus 11.1 ± 1.6). At 10 weeks, administration of NTX significantly increased eye wipes in the injury group (15.4 ± 1.6), but not in the sham group (11.1± 0.7) (p<0.05). At 16 weeks, topical administration of NLX-me increased eye wiping in the injured mice, but not control mice (16.3 ± 2.2 versus 10.8 ± 2.3) (p<0.01).
Alkali burn leads to chronic sensitization in the oculo-trigeminal tract. These neuropathic changes are modulated by MOR at the level of the peripheral nervous system. This study unveils an important mechanism of ocular neuropathic pain modulation. Our results support the existence of a novel target for diagnosis and treatment of chronic ocular pain.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Alkali burn to the ocular surface increases eye-wiping behavior in mice compared to sham treated control mice. This behavior resolves after 28 days. Subcutaneous naltraxone (NTX) or topical naloxone methioidide (NLX-me) reinstates increased eye wiping in injured but not control eyes.
This PDF is available to Subscribers Only