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Tramadol Eye Drop Reduces Ocular Nocifensive Behavior Not Primarily Mediated by μ-Opioid Receptor Activation in a Rat
Shogo Nagaoka1,2, Yoshihiro Takai1, Takeshi Kiyoi2
1Rohto Pharmaceutical Co., Ltd., 6-5-4 Kunimidai, Kizugawa, Kyoto 619-0216, Japan.
Abstract:
This study aimed to explore the possibility of using a novel eye drop for ocular pain in dry eyes by examining the effect of tramadol eye drops on nocifensive behavior in normal and dry eye rats. Dry eye model rats were generated by the unilateral surgical excision of the extraorbital lacrimal glands. The effect of tramadol eye drops on ocular pain in normal and dry eye model rats was assessed using the eye closure time induced by a hyperosmolar (5 M NaCl) solution and the transient receptor potential vanilloid 1 (TRPV1) agonist (1 mM capsaicin). The current response induced by 1 μM capsaicin in the primary sensory neurons was measured by whole-cell recording using cultured trigeminal ganglion neurons. Extraorbital lacrimal gland excision (LGE) significantly enhanced the ocular nocifensive response induced by a 5 M NaCl solution. Pretreatment with tramadol eye drops transiently suppressed nocifensive behavior on the ocular surface in sham-operated and dry eye rats. The suppressive effect of tramadol was only effective on the ipsilateral eye and was not canceled by a μ-opioid receptor antagonist. Furthermore, the capsaicin-induced nocifensive behavior and current responses in primary sensory neurons were suppressed by tramadol treatment. Tramadol eye drops have been shown to temporarily relieve ocular pain in normal and hyperalgesic conditions, such as dry eye. The underlying mechanism may be a decrease in TRPV1-mediated responses at the peripheral sensory nerves on the ocular surface, not primarily mediated by μ-opioid receptor activation.
Insights
Tramadol eye drops may offer temporary relief for ocular pain in dry eye conditions. This study found tramadol reduced pain responses by affecting sensory nerves, not opioid receptors.
Area of Science:
- Ophthalmology
- Neuroscience
- Pharmacology
Background:
- Dry eye disease (DED) is a prevalent condition characterized by ocular discomfort and pain.
- Ocular pain in DED can significantly impact patients' quality of life.
- Novel therapeutic strategies for managing ocular pain in DED are needed.
Purpose of the Study:
- To investigate the efficacy of novel tramadol eye drops in alleviating ocular pain.
- To examine the effect of tramadol on nocifensive behavior in normal and dry eye rat models.
- To elucidate the underlying mechanism of tramadol's action on ocular pain pathways.
Main Methods:
- A dry eye model was created in rats via surgical excision of extraorbital lacrimal glands.
- Ocular pain was assessed using eye closure time induced by hyperosmolar saline and capsaicin.
- Neuronal responses were measured using whole-cell recordings from cultured trigeminal ganglion neurons.
Main Results:
- Dry eye induction enhanced nocifensive responses to hyperosmolar saline.
- Tramadol eye drops transiently suppressed ocular surface nocifensive behavior in both normal and dry eye rats.
- Tramadol reduced capsaicin-induced pain behaviors and neuronal responses, suggesting TRPV1 involvement.
Conclusions:
- Tramadol eye drops provide temporary relief from ocular pain in normal and dry eye conditions.
- The analgesic effect appears mediated by a reduction in TRPV1-dependent responses at peripheral sensory nerves.
- The mechanism does not primarily involve μ-opioid receptor activation.
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