North Andover, Mass.
What's the Difference?
The distinction between anesthesia and analgesia is subtle, but knowing the words' Greek roots can help. The word anesthesia is composed of the prefix "an" meaning negative and the word "aisthesis" meaning sensation, while analgesia is composed of "an" plus "algesis," meaning "no pain." As such, the former refers to more of a larger-scale absence of sensation while the latter refers to the absence of pain.
In medicine, anesthesia is defined as the loss of sensation, usually by damage to a nerve or a receptor. It's also the inability to feel pain as a result of a drug or other medical intervention. Analgesia is the absence of sensibility to pain, or relief of pain without unconsciousness.1
Topical Anesthetics
The first topical anesthetic used in ophthalmology was an extract of Erythroxylon coca, commonly known as cocaine.2 Cocaine was used in ophthalmic surgery from 1884 until the first synthetic topical anesthetic, Procaine, was developed in 1905. Since then, numerous other topical anesthetics have been developed. Yet, unlike cocaine, these agents have a more favorable side-effect profile, a lower potential for abuse and are more widely available.2
• Mechanism of action. Topical anesthetics used in ophthalmology function by blocking nerve conduction in the superficial cornea and conjunctiva.2 The ocular surface is innervated by the multiple branches of the trigeminal nerve. The cornea is supplied by the long and short ciliary nerves, the nasociliary nerve and the lacrimal nerve.
Anesthetics prevent the temporary increase in sodium permeability that occurs during nerve-impulse conduction.2 Without the ability of the nerve cell to generate action potentials, the nerve impulse is blocked and sensation is eliminated.2 There are several hypotheses as to why this may occur. Anesthetics may interfere directly with channel activation by decreasing the number of available channels, they may inhibit the conformational change that the channels undergo when opening or they may reduce the ion flow through the open channels.3 The length of the anesthetic effect is defined by the time it takes for the anesthetic molecules to diffuse out of the nerve and be removed by the circulatory system.3
• Adverse effects. Although topical anesthesia has a more favorable risk profile than retrobulbar or peribulbar anesthesia, adverse events can occur with its use. One such adverse effect is alteration of lacrimation and tear-film stability. Topical anesthetics disrupt surface microvilli of the epithelial cells, causing decreased stability in the tear film. Anesthesia also lessens mucous adherence, shortens tear breakup time, decreases the blink rate and blocks the reflex-tearing pathway, resulting in inadequate tear production in response to noxious stimuli. Combined, these effects contribute to the deterioration of the ocular surface by increasing dry-eye symptoms, staining and vulnerability.2
Other detrimental effects of topical anesthetics include the potential for epithelial toxicity, local allergic reactions, interference with diagnostic tests (i.e., reduced Schirmer's reliability and the hypofluorescence of sodium fluorescein) or changes in epithelial permeability that might affect the efficacy of other topical agents.
In practice, then, before choosing an anesthetic, consider the agent's time until onset of action, duration, irritant effect, allergenicity and preservative. A list of currently available topical anesthetics appears in Table 1.
The potential for abuse of topical anesthetics is most often found in patients who present with keratitis and persistent epithelial defects and find that their pain can be relieved only by anesthetics. Overuse of topical anesthetics results in poor healing of epithelial defects and stromal infiltration. A grayish-yellowish ring of infiltrate will be evident around the epithelial defect and the eye will be inflamed with stromal thickening.
Table 1. Topical Anesthetics
Active Ingredient/Concentration
Trade Name
Benoxinate 0.4%
Fluress (Akorn)
Proparacaine 0.5%
Ophthetic Ophthalmic Solution (Allergan)
Fluoracaine (Akorn)
Proparacaine Hydrochloride (Akorn)
Proparacaine Hydrochloride Ophthalmic Solution (Bausch & Lomb)
Tetracaine 0.5%
Tetracaine Hydrochloride Dropperettes (Novartis)
Tetracaine Hydrochloride Ophthalmic Solution (Bausch & Lomb)
Topical Analgesics
Topical non-steroidal anti-inflammatory agents are used both pre- and postoperatively to aid in wound healing and pain management. They're used for cataract surgery patients to treat pre- and postoperative inflammation, to prevent intraoperative miosis and to prevent pseudophakic cystoid macular edema or treat CME after surgery. Postop treatment with NSAIDs can also be effective in re-establishing the blood-aqueous barrier. In addition, though preoperative use of NSAIDs isn't standard procedure, recent research has suggested that preop NSAIDs can reduce the amount of inflammation after surgery.4 NSAIDs can also reduce discomfort after refractive surgery.4
There are a number of benefits with analgesics in contrast to anesthetics that make them useful for patient administration. First, unlike in systemic opioids, long-term NSAID use poses no risk of addiction. NSAIDs are most effective when pain accompanies inflammation from injury. By reducing low or moderate levels of pain, NSAIDs have a built-in safety measure, allowing patients to be aware of severe pain that could indicate a more serious problem and the need to see a physician.
• Mechanism of action. There are elevated levels of prostaglandins in the aqueous humor after surgical procedures or trauma to the eye.5 Prostaglandins interact with other inflammatory mediators, such as substance P and bradykinin, to sensitize pain receptors to other mediators.6 NSAIDs don't have any effect on preformed prostaglandins, but the anti-inflammatory effects of NSAIDs originate from their ability to reduce prostaglandin synthesis. This reduction in overall prostaglandin levels decreases pain.
NSAIDs function by blocking cyclooxygenase (COX), a key enzyme in the arachidonic acid metabolism pathway. It's this inhibition of COX that results in decreased prostaglandin synthesis. Research has shown prostaglandins to have chemokinetic activity and the ability to serve as mediators of the inflammatory response associated with pain and allergic reactionse7 Prostaglandins also produce other effects in the eye, including miosis, increased permeability of the blood-ocular barrier, changes in intraocular pressure and hyperemia.7
Leukotrienes are also important mediators in the inflammation pathway that contribute to the symptoms of inflammation. While NSAIDs' best-understood mechanism of action is the prohibition of prostaglandin synthesis, they have also been shown to indirectly reduce leukotrienes.
Table 2. Topical NSAIDS
Active Ingredient/Concentration
Trade Name
Diclofenac 0.1%
Voltaren Ophthalmic (Novartis)
Flurbiprofen 0.03%
Ocufen (Allergan)
Flurbiprofen Sodium Ophthalmic Solution (Bausch & Lomb)
Ketorolac 0.5%
Acular (Allergan)
• Adverse effects. The most common adverse effects associated with topical NSAIDs are transient burning, stinging and conjunctival hyperemia.4,8 Other rare effects include post-cataract surgery atonic mydriasis, contact dermatitis, corneal infiltrates, epithelial defects or superficial punctate keratitis.4 In rare instances, topical NSAIDs have been associated with more severe adverse events such as indolent corneal ulceration and full-thickness corneal melts, but these cases were with the concurrent usage of topical corticosteroids or antibiotics. Despite the possible side effects, NSAIDs provide a positive benefit-risk ratio when used appropriately.4,8
Potentially, topical NSAIDs can be absorbed through the nasal mucosa and produce systemic effects. Systemic side effects are rare, but symptoms of bronchial asthma can occur.8
Future Directions
While both anesthetics and analgesics relieve pain, the differences in their mechanisms of action impact their use. The management of pain in ophthalmology is an evolving field where experts seek new drugs to provide relief with minimal side effects.
An example of a new analgesic is Allergan's recently approved lower concentration of Acular (0.4%), indicated for the reduction of pain and burning following refractive surgery.
The Adolor company (Exton, Pa.) is using cloned human opioid receptors to create non-narcotic and anti-hyperalgesic medications that are impermeable to the blood-brain barrier. Adolor's ADL 2-1294 (loperamide) is an example of a mu-receptor antagonist that researchers are studying as an analgesic without the addictive potential normally associated with opioids. In a proof-of-concept study, loperamide reduced the pain caused by corneal abrasions, embedded foreign bodies and pterygium excision. (Nevius J, ARVO Abstract #4917, 2000) The focus on opioid receptors may produce a novel class of analgesic compounds that are superior to current drugs.
Dr. Abelson, an associate clinical professor of ophthalmology at Harvard Medical School and senior clinical scientist at Schepens Eye Research Institute, consults in ophthalmic pharmaceuticals. Ms. Rosner and Ms. MacDonald are research associates at Ophthalmic Research Associates in North Andover.
1. Dorland's Illustrated Medical Dictionary. 28th ed. Philadelphia: W.B. Saunders Company, 1994.
2. Rosenwasser, G. Complications of topical ocular anesthetics. International Ophthalmology Clinics 1989;29:3:153-158.
3. Acquadro, MA. Anesthetics. In: Albert DM and Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia: WB Saunders Co., 1994:929-940.
4. Schalnus, R. Topical non-steroidal anti-inflammatory therapy in ophthalmology. Ophthalmologica 2003;217:89-98.
5. To, K et al. Nonsteroidal Antiinflammatory Drugs. In: Albert DM and Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia: WB Saunders Co., 1994:1022-1027.
6. Davies, P and MacIntyre, EM. Prostaglandins and Inflammation. In: Gallin JI, Goldstein IM, and Snyderman R., eds. Inflammation: Basic Principles and Clinical Correlates, 2nd Ed. New York: Raven Press, 1992:123-138.
7. Flach, AJ. Topical non-steroidal antiinflammatory drugs for ophthalmic use. International Ophthalmology Clinics 1996;36:2:77-83.
8. Gaynes, BI and Fiscella, R. Topical NSAIDs for ophthalmic use: a safety review. Drug Safety 2002;25:4:233-250.
