neurotensins ( including neurotensin , neurotensin analogs , or neurotensin receptor agonists ), alone or in combination with opiates , have been found to have significant topical analgesic effect . various neurotensin receptor agonists include , without limitation , those described in u . s . pat . nos . 6 , 858 , 396 ; 6 , 783 , 946 ; 6 , 566 , 330 ; 6 , 358 , 922 ; and 6 , 043 , 218 , each of which are incorporated herein by reference in their entirety . the sequences of compounds nt69 , nt71 , and nt72 , which are neurotensin analogs that contain neo - trp at position 11 of the natural neurotensin sequence , are listed in table 1 below . these neo - tryptophan - containing analogs are resistant to degradation by proteases . other neo - tryptophan containing neurotensin analogs can be found in u . s . application ser . nos . 11 / 800 , 975 , filed may 7 , 2007 and 11 / 709 , 991 , filed feb . 23 , 2007 . all of the above - mentioned applications and patents are hereby expressly incorporated by reference in their entirety . topical application of neurotensins ( nts ) has the advantage of eliminating systemic side - effects attributable to the drug , such as hypotension , which may be problematic with neurotensins that bind both nts1 and nts2 receptors . systemic absorption ( blood levels ) following topical application for any nt compound is known to be minimal because : 1 . typically , blood levels are & lt ; 10 % of total dose following topical administration of drugs in the eye , such as beta - blockers . hypotension , for example , one of the main effects of beta - blockers , is not associated with topical use . 2 . topical application of neurotensin on rat tail in a dmso solution caused analgesia in the segment of the tail covered with the drug but not a neighboring segment of the tail not exposed to the drug , indicating that systemic absorption did not occur . determination of topical analgesic effect of neurotensin analogs in a mouse tail flick model antinociception ( reduction of sensitivity to painful stimuli ) can be measured using pain tests such as tail flick studies . tail flick studies typically involve subjecting an animal to a painful stimulus ( e . g ., heat or a pin prick ), and measuring the length of time or amount of pinching force applied before the animal physically responds to the stimulus by flicking its tail . in this mouse tail flick model , the distal end region of the mouse &# 39 ; s tail was immersed approximately 3 cm into a dmso solution containing nt72 at concentrations of 2 mg / ml and 5 mg / ml . analgesia was then determined using a radiant heat tailflick test in which a focused beam of light was targeted on the tail and latency before the animal removed its tail from the painful stimulus was measured . as seen in fig1 , there was little effect on the proximal tail ( i . e ., the portion not exposed to the drug ) when compared to baseline . the portion of the tail exposed to nt72 , however , showed a very robust result with the animals waiting at least 4 seconds before removing their tails . as apparent from the increased latency of tail flicks , nt72 induces analgesia in this portion of the tail but not elsewhere . therefore , the analgesic effect produced is a local one and not secondary to systemic absorption of the drug . additionally , the analgesic effect was as robust as that of morphine ( not shown ). fig2 and 3 illustrate the topical analgesic effect of various neurotensin analogs ( nt67 , nt69 , nt71 , nt72 , and nt76 ). nt71 and nt72 applied to the distal third of a mouse tail showed a more robust analgesia than the other neurotensin analogs , with the animals waiting approximately 5 seconds before they reacted to the painful stimulus ( see fig2 ). as seen in fig3 , an analgesic effect (& gt ; 30 % increase in latency ) was found in about 50 % of the mice tested for nt71 and in about 60 % of the mice tested for nt72 . determination of topical corneal anagesic effect in an ocular pain model in rabbit the purpose of the study was to determine whether neurotensin analogs had topical analgesic action in the rabbit eye . new zealand white rabbits were used and corneal analgesia was measured using a cochet - bonnet aesthesiometer . twenty - four rabbits , each weighing 2 - 3 kg , were tested . animals were randomized to three groups . each group of two animals received one of three neurotensin compounds , nt69 , nt71 ( sar001 ), or nt72 ( sar002 ). baseline corneal sensation was determined using a hand - held cochet - bonnet aesthesiometer ( luneau opthalmologie , paris , france ). to obtain a measurement , the cornea was viewed at close range from the side while the aesthesiometer was advanced with perpendicular corneal contact until flexure of the filament was observed . the lowest pressure was used initially ( 30 - 40 mm filament length ), and measurements proceeded in an ascending fashion . the highest pressure was at a filament length of 10 mm . at each predetermined length , six measurements were made . from these measurements , the number of blinks ( out of 6 ) that occurred at any given length was calculated at baseline ( bss or saline control ), and at 15 , 30 , 60 , 90 , 150 , 210 , and 240 minutes following the administration of the test compound . the dose of each compound was calculated from the known ed50s of the drugs . a dose that was several fold higher than the ed50 was given , on the assumption that the vast majority would be washed out in tears . approximately 50 - 70 μl aliquots of the following solutions were placed in the eyes ( nt69 ( 1 . 2 mg / ml ), nt71 ( 1 mg / ml ), and nt72 ( 1 mg / ml ). as seen in fig4 , all three neurotensin analogs ( nt69 , nt71 ( sar001 ), or nt72 ( sar002 )) abolished corneal sensation ( no blink response to the strongest stimulus , 10 mm hairs ), and for prolonged periods of time . nt69 had a very fast onset ( no blink response at 15 minutes after administration ) that lasted for at least 90 minutes . nt71 and nt72 had slower onsets compared to nt69 but a longer duration of action — there was no blink response at 30 minutes after administration and the analgesic effect lasted at least 150 minutes for nt72 and at least 210 minutes for nt71 . fig5 a - c illustrate the dose response curves for nt71 and nt72 at 15 and 30 minutes and nt69 at 30 minutes following topical administration of specific doses of neurotensin analog into the eye . twenty - four rabbits were each tested three times over a 24 - hour period . baseline was established in both eyes . approximately 50 - 70 μl of the indicated concentration of drug was applied to the rabbit &# 39 ; s eye . changes in the blink response were recorded for 4 hours ( or until return to baseline ). doses show that the neurotensin analogs induce analgesia in the rabbit eye at doses as low as about 0 . 1 to about 0 . 3 mg / ml . irritant effects of the compounds and of the saline solution were tested by examining each eye at baseline , after instilling bss ( buffered saline solution ), and 5 minutes and 1 hour after administration of test compound . redness , chemosis , tearing , and corneal opacity were evaluated in all eyes using the draize scoring method . no abnormalities were noticed . a major drawback of current topical anesthetics is the inhibition of corneal epithelial cell migration with delay of wound healing . neurotensin compounds deliver analgesic effect without inhibition or delay of corneal healing . this distinguishes the neurotensin topical analgesics from the local anesthetics and from nsai ( non - steroidal anti - inflammatory ) eye drops , all of which delay wound healing . this is a very important distinction for the neurotensins because delayed healing increases the risk of complications following eye surgery . based on tests of neurotensin analogs in the eye , we have unexpectedly discovered that neurotensins are effective analgesic agents in the eye . experimental data for nt69 , sar001 ( also known as nt71 ), and sar002 ( also known as nt72 ) show prolonged and profound analgesia in an established ocular pain model in the rabbit . the limbus was removed from both eyes of anesthetized rabbits and dissected to include 1 . 0 to 1 . 5 mm peripheral cornea and 1 . 0 to 1 . 5 mm beyond the anatomical limbus . each limbus was divided into four small segments . two segments were used for each 60 mm square plate . cultured rabbit corneal epithelial cells were utilized to measure the closure of a scratch made in a confluent epithelial monolayer in the presence of varying doses of the test compounds ( 0 . 1 mg / ml to 10 mg / ml ). uniform scratches were made in confluent monolayers of primary rabbit corneal epithelial cells (“ in vitro scratch assay ”). individual cell migration assays were performed in the presence of the test compounds and compared with standard doses of tetracaine and proparacaine . movement of cells from the edge of the scratch ( wound ) toward the middle of the scratch ( wound ) were measured over 24 hours . as seen in fig6 , cells in which the control ( pbs ), nt71 , or nt72 were added in various concentrations resulted in a much larger migration of cells over the 24 hour period as compared to wounds in which proparacaine and tetracaine were added . cells in which nt71 and nt72 were added migrated at least 40 μm , alternatively at least 50 μm , alternatively at least 60 μm , alternatively at least 70 μm over 24 hours . the rate of closure of the in vitro wounds were measured in the presence of traditional na + - channel blocking anesthetics ( proparacaine or tetracaine ) or neurotensin agonists nt71 ( sar001 ) or nt72 ( sar002 )) at two concentrations ( 0 . 1 mg / ml and 0 . 5 mg / ml ). as apparent from fig7 - 9 , the monolayer scratch was closed much more rapidly with neurotensin analogs than with tetracaine or proparacaine . there was very little closure of the wounds in which proparacaine and tetracaine were added . tetracaine caused the greatest delay in monolayer closure . in fact , scratches treated with either proparacaine or tetracaine did not close . in contrast , control cells substantially closed the defect within 24 hours , sar001 ( nt71 ) and sar002 nt72 ) at both lower ( 0 . 1 mg / ml ) and higher ( 0 . 5 mg / ml ) doses did not inhibit the rate of scratch closure as compared to control , in fact , low dose sar001 cnt71 ) and high dose sar002 ( nt72 ) may accelerate rate of scratch closure . scratches in which neurotensin analogs ( sar001 ( nt71 ) and sar002 ( nt72 )) were added showed at least 80 % closure within at least 15 hours , alternatively within at least 20 hours , alternatively within at least 25 hours . additionally , many concentrations of the neurotensin analogs resulted in faster healing over the control ( pbs ). in vitro cytotoxicity studies were performed in intact rabbit cornea . proparacaine ( 0 . 5 mm , 1 mm , 5 mm , and 10 mm ), tetracaine ( 0 . 5 mm , 1 mm , 5 mm , and 10 mm ), nt71 ( 0 . 1 mg / ml ( 0 . 13 mm ), 0 . 25 mg / ml ( 0 . 32 mm ), and 0 . 5 mg / ml ( 0 . 63 mm )), nt72 ( 0 . 1 mg / ml ( 0 . 15 mm ), 0 . 25 mg / ml ( 0 . 38 mm ), and 0 . 5 mg / ml ( 0 . 76 mm )), and 70 % meoh were added to intact rabbit corneas . the percentage of living cells was determined over a 24 hour period using light microscopy and fluorescence . as apparent from fig1 a , tetracaine was cytotoxic to the conical cells at concentrations as low as 0 . 5 mm , resulting in the death of about half of the corneal cells observed . administration of 1 mm tetracaine resulted in the death of almost all of the corneal cells observed . similarly , administration of 5 mm proparacaine resulted in the death of almost all of the corneal cells . in contrast , as seen in fig1 b , administration of nt71 and nt72 resulted in very limited cell toxicity ( less than approximately 20 % of the corneal cells died , alternatively less than approximately 25 % of the corneal cells died , alternatively less than approximately 30 % of the corneal cells died , compared to untreated cells ). in vivo superficial keratotomy experiments were performed on rabbits to access healing effects in an animal model . starting with equivalent circular wounds of 6 . 5 mm diameter ( 33 mm 2 ), after 36 hrs of administration every 2 hours of 1 mg / ml nt71 ( sar001 ), nt72 ( sar002 ), tetracaine or saline ( control ), the persistent epithelial defect ( wound ) size was : after 48 hours , wounds treated with control ( saline ), nt71 ( sar001 ), and nt72 ( sar002 ) were fully healed . the tetracaine residual epithelial defect was still present . administration every 2 hours of neurotensins at 1 mg / ml in a cornea with open epithelium did not cause any notable adverse ocular effect in the rabbits slit lamp examination . no additional conjunctival injection , no corneal opacification , no anterior chamber cell or flare as compared to control . thus , unlike proparacaine and tetracaine , which inhibit epithelial cell proliferation and therefore inhibit healing , sar001 ( nt71 ) and sar002 ( nt72 ) can be used in pain management without a compromise in healing . for example , 0 . 1 mg / ml or less , 0 . 5 mg / ml or less , 1 mg / ml or less , 3 mg / ml or less , 5 mg / ml or less , 7 mg / ml or less , or 12 mg / ml or less of neurotensin or neurotensin analog can be applied as a topical analgesic for pain management following eye surgery and the patient will experience substantial healing in about the same time as if no analgesic had been used for pain management with use of topical neurotensin analgesics . substantial healing may occur in 90 % or less of the time as if no analgesics had been applied , alternatively 100 % or less , alternatively 110 % or less , alternatively 120 % or less , alternatively 150 % or less , or alternatively 200 % or less . substantial healing may occur within 24 hours or less , alternatively 36 hours or less , alternatively 48 hours or less , alternatively 60 hours or less , alternatively 72 hours or less , or alternatively 84 hours or less . anesthetized rabbits were placed under an operating microscope , a sterile lid speculum placed in the right eye , and a 6 . 5 mm trephine used to make a partial thickness epithelial cut centered on the pupil . a sterile beaver blade was used to remove the epithelium within the area of demarcation . a single drop of moxifloxacin 0 . 1 % was instilled at the end of the procedure . the speculum was removed and the animal allowed to recover from the systemic anesthesia . the topical agent under investigation was placed in the eye every 4 hours for 5 days . neurotensin analogs sar001 ( nt71 ), sar002 ( nt72 ), and 69 ( nt 69 ) at 0 . 6 mg / ml or 0 . 5 % proparacaine or vehicle were instilled at the end of the procedure . the control animals underwent the same surgical procedure . at the end of the procedure , 0 . 5 % proparacaine or vehicle was instilled in the eye every 4 hours . fluorescein ( 1 %) was instilled into the eye at times 0 , 1 , 2 , 6 , 12 , 36 , 48 , 72 , 96 , and 120 hours after the procedure and the size of the epithelial defect measured via slit lamp photography . the animals were scored for degree of blinking , tearing , conjunctival injection , anterior chamber inflammation , and intraocular pressure . the epithelial defect disappeared within 72 hours in all neurotensin treated animals . disappearance of the defect was delayed to 96 - 120 hours in the proparacaine - treated animals and was incomplete in 40 % of animals at this time point . anesthetized rabbits were placed under an operating microscope , a sterile lid speculum placed in the right eye , and a 6 . 5 mm excimer laser ablation of 75 microns centered on the pupil was made using a ladarvision 4000 excimer laser . a single drop of moxifloxacin 0 . 1 % was used at the end of the procedure . sar001 ( nt71 , 0 . 1 % w / w ), sar002 nt72 , 0 . 1 % w / w ), or nt69 was instilled at the end of the procedure and repeated at 4 hour intervals . control animals underwent the same surgical procedure . standard doses of tetracaine ( 0 . 5 % w / w ) or proparacaine ( not shown ) were instilled at the end of the procedure and at 4 hour intervals thereafter . fluorescein ( 1 %) was instilled into the right eye at times 0 , 1 , 2 , 6 , 12 , 36 , 48 , 72 , 96 , and 120 hours after the procedure and the size of the epithelial defect measured via slit lamp photography . degree of blinking , tearing , conjunctival injection , anterior chamber inflammation , and intraocular pressure were evaluated . as seen in fig1 , the epithelial defect disappeared within 48 hours in the control and neurotensin analogtreated animals . furthermore , the wound was closed at least 80 % in at least about 36 hours , alternatively at least 90 % in at least about 40 hours , alternatively at least about 100 % in at least about 48 hours in the neurotensin analog - treated animals . disappearance of the defect was delayed 96 - 110 hours in the tetracaine - treated animals and was incomplete in 50 % of the tetracaine - treated animals . neurotensin analogs can be formulated in combination with lubricant eve drops , artificial tears , or methylcellulose drops for the treatment of dry eye syndrome , corneal lacerations , or eye trauma . these conditions are characterized by pain , which can be relieved by artificial tears and lubricants and by analgesic eyedrops such as neurotensin analogs . formulations also include combinations of neurotensin analog drops with morphine drips , which combinations are synergistic . suitable formulations also include neurotensin analogs and local anesthetic eye drops , both of which relieve pain . local anesthetics such as tetracaine , however , delay wound healing whereas neurotensin analogs do not delay wound healing . in fact , neurotensin analogs were found to accelerate wound healing , thus reducing unwanted side effects of local anesthetics . combinations of neurotensin analogs formulated with non - steroidal anti - inflammatory eye drop ( nsai ed ), and indeed any other eyedrop can be used for relief of eye pain . although the foregoing invention has , for the purposes of clarity and understanding , been described in some detail by way of illustration and example , it will be obvious that certain changes and modifications may be practiced which will still fall within the scope of the appended claims .