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Show Journal of Neuro- Ophthalmology 18( 1): 17- 20, 1998. © 1998 Lippincott- Ravcn Publishers, Philadelphia The Treatment of Periocular and Facial Pain with Topical Capsaicin Norah S. Lincoff, M. D., Pamela P. Rath, M. D., and Michio Hirano, M. D. This article describes the effects of topically applied capsaicin ( a nociceptive substance- P suppressor) in patients with neuropathic periocular or facial pain. Peripheral neuropathic pain is a major cause of periocular or facial discomfort and usually follows injury to a subcutaneous peripheral nerve. Though the damage is local, the pain tends to radiate. We studied three patients who complained of a 2- to 30- year history of fluctuating pain in the periocular area. All three had an area of point tenderness that responded to the topical application of capsaicin cream. Key Words: Periorbital pain- Facial pain- Capsaicin- Trigeminal neuralgia. Facial pain and, more specifically, periocular pain may be caused by intraocular inflammatory syndromes, migraine, trigeminal neuralgia, or temporomandibular joint pain. Peripheral neuropathic pain is a local phenomenon that can masquerade as a more diffuse headache syndrome, but is actually secondary to direct damage of a subcutaneous peripheral nerve branch of the trigeminal system ( 1,2). It is usually caused by blunt trauma, postsurgical trauma, or inflammatory disease states. The treatment of this type of local pain syndrome is challenging because nonsteroidal anti- inflammatory agents ( NSAIDs) provide only minimal relief, and narcotics- while effective in moderating pain- can be addictive. Topical capsaicin, which is not an anesthetic agent, acts directly on the damaged nerve ending, thereby interrupting the impulse that causes the central nervous system to perceive pain. Capsaicin ( trans- 8- methyl-./ V- vanillyl- 6- nonenamide), a component of the red chili pepper, depresses the function of type- C nociceptive fibers by depleting substance P, the principal neurotransmitter of pain, from synaptic terminals ( 3- 6). Capsaicin has been effective in managing other pain- Manuscript accepted 7/ 16/ 97. From the Department of Neurology and Ophthalmology ( N. S. L., P. P. R.), School of Medicine and Biomedical Sciences, State University of New York, Buffalo; and Department of Neurology ( M. H.), College of Physicians and Surgeons, Columbia University, New York, New York, U. S. A. Address correspondence and reprint requests to Dr. N. S. Lincoff, Department of Neurology, Buffalo General Hospital, 100 High Street, Buffalo, NY 14203, U. S. A. ful conditions, such as rheumatoid arthritis, diabetic peripheral neuropathy, trigeminal neuralgia, postherpetic neuralgia, and postmastectomy pain ( 7- 17). PATIENTS AND METHODS We treated three patients ( one man and two women) who suffered from severe periocular pain that we believe was neurogenic in origin ( Table 1). All three patients could localize one specific area of tenderness from where their pain syndrome appeared to radiate. The patients had been referred because of failed treatment with at least one of the following medications: NSAIDs, corticosteroids, neuroleptic agents, and antidepressants. Duration of symptoms ranged from 2 to 30 years and was unremitting. The patients described either a deep aching or burning pain ( 18), but otherwise had normal facial sensation. The patients were instructed to apply 15 mg of capsaicin cream ( 0.075%) twice per day to the area of most intense pain. They were told how to apply the cream and were warned to avoid accidental ocular contact. Reassurance was given that the initial burning sensation of the skin would be temporary. The three cases were followed for at least 1 year. CASE REPORTS Case 1 This 71- year- old white man was seen in neuro-ophthalmologic consultation because of a 1- year history of chronic lancinating pain around his left eye; this pain radiated toward the left frontal area. An area over the left infraorbital nerve was the region of the most intense pain and was tender to touch ( Fig. 1). Though the patient had no history of trauma, he had undergone cataract surgery with a retrobulbar block to the left eye just prior to the onset of his pain syndrome. Prior to our examination, amitriptyline, nortriptyline, trazodone, and Ativan ( lor-azepam) were tried with little or no relief. The results of sinus radiographs, computed tomography, magnetic resonance imaging ( MRI), complete blood count, determination of the erythrocyte sedimentation rate, and a workup for vasculitis were normal. Our first examination was on October 27, 1993. His 17 18 N. S. L1NC0FF ET AL. TABLE 1. Summary of patient results Patient SB MB RS Age 71 61 74 Duration of symptoms at 1st visit 1 year 3 years 30 years Results Excellent Good Good 3 Mo. status No pain using Capsaicin 0.075% once a day Mild pain well controlled using 0.075% Capsaicin once a day Mild pain well controlled using 0.075% Capsaicin two times a day 6 Mo. status No pain using Capsaicin 0.075% once a day Mild pain well controlled using 0.075% Capsaicin biweekly Mild pain well controlled using 0.075% Capsaicin two times a day 1 Yr. status No pain off Capsaicin Mild pain well controlled using Capsaicin 0.075% once a week Pending best corrected vision was 20/ 25 bilaterally. Mild nuclear sclerosis was present in his right eye, and an intraocular lens implant with a posterior subcapsular cataract was present in his left. The results of slit- lamp and fundus-copic examinations were unremarkable. His pupils were normal. The intraocular pressure by applanation tonometry was 14 in each eye. The findings on exophthalmom-etry were normal and symmetrical. On external examination, there was obvious point tenderness over the area of his left infraorbital nerve. We treated the patient's area of point tenderness with topical capsaicin cream twice a day. He reported dramatic relief of his symptoms by day 10 of treatment. Tapering of the cream to once a day provided continued relief of the patient's neuropathic pain. Discontinuation of the topical treatment at 2 months led to a recurrence of the pain syndrome. Reinstitution of the treatment provided repeat relief of the patient's symptoms within 7 days. The patient continued to have relief of his pain with periodic use of capsaicin cream for 1 year and was then able to discontinue treatment. At 3 years since the initial use of capsaicin, he remains pain free. Case 2 This 61 - year- old white woman presented with a 3- year history of right periocular pain. Her periocular pain would at times radiate to the right side of her scalp and down toward her neck, but she could always localize an area of specific point tenderness over her right trochlea. The pain was exacerbated by extensive reading. She never suffered from any symptoms of double vision. Her past medical history was significant for rheumatoid arthritis and mild hypertension. At the time of her evaluation, she was taking 10 mg of prednisone a day and a NSAID, with relief of her rheumatoid pain and mild relief of her periocular pain. Her prior workup, done 1 year before, included an MR1 of the brain, the results of which were normal. Our first examination was on September 7, 1995. Her best corrected visual acuity was 20/ 25 in each eye. Results of the external examination were significant for mild dermatochalasis but no periocular swelling. She had definite tenderness on palpation of her right trochlear area. Her pupils were normal. Slit- lamp examination revealed early posterior subcapsular cataracts bilaterally. Motility was unremarkable, with no evidence of a vertical deviation; superior oblique function was normal bilaterally. Intraocular pressures were normal. Results of a funduscopic examination were unremarkable. The patient was started on a topical application of capsaicin cream twice a day to the right trochlear area, and her symptoms were relieved within 14 days. She was asked to refrain from extensive reading during the initial treatment period. She was able to taper her dose to once a day, and then to biweekly, with continued relief of her pain at 6 months. Case 3 This 74- year- old white woman presented with a 30- year history of chronic left facial pain that would radiate from a pinpoint area in the left nasal fold to her left cheek, her periorbit, and occipital area. It was exacerbated by chewing. Intraorally, she could pinpoint the same area of tenderness between her gum and maxillary bone. The pain would become progressively more intense through the day. In 1983, because of worsening of her symptoms, she underwent an extensive medical workup, which had included an MRI of the brain, computed tomography of the brain, sinus radiographs, orthodontic radiographs, a vas-culitic workup, and temporal artery biopsy, the results of all of which were normal. Past medical treatment trials included Tegretol ( carbamazepine), Toradol ( ketorolac tromethamine), NSAIDs, and numerous antidepressants with little or no relief. Elavil ( amitriptyline) provided some relief at bedtime. The patient's past medical history was significant for Paget's disease of her left femur and for osteoarthritis. On review of systems, the patient described a significant dental history that included extraction of all of her teeth for cosmetic purposes at the age of 18. She has required chronic dental procedures since that time for proper bridge fittings. Our first examination was on December 1, 1995. Her best corrected visual acuity was 20/ 25 in each eye. Slit-lamp examination revealed an early tear- film breakup time but no evidence of keratitis. The pupils were unremarkable, and the intraocular pressures were normal, as were results of the funduscopic examination. She had no facial swelling or redness. Point tenderness was elicited at her left nasolabial fold. The patient was treated with topical capsaicin cream to her left nasolabial fold twice per day with moderate relief of her local pain and complete relief of her radiating pain J Neiiro- Ophthalmol, Vol. IS, No. 1, 1998 PERIOCULAR PAIN AND TOPICAL CAPSAICIN 19 FIG. 1. Case 1: point tenderness in the area of the left infraorbital nerve and the pattern of the patient's referred pain. within 14 days. At 9 months, using the cream twice a day, she remains symptomatically much improved. DISCUSSION Our cases provide evidence that relief can be obtained for some patients who suffer from periocular pain of neuropathic origin who have failed to improve with standard medical treatment. Capsaicin has been effective in managing other painful conditions, including rheumatoid arthritis, diabetic neuropathy, postherpetic neuralgia, trigeminal neuralgia, migraine, and postmastectomy pain ( 7- 17). We have treated three patients with capsaicin who suffer from periocular and facial pain felt to be neuropathic in origin. Their pain probably stems from damage or inflammation of terminal branches of the trigeminal sensory system. Patient 2 describes pain in the area supplied by the ophthalmic division of the trigeminal nerve ( infratrochlear nerve), whereas patients 1 and 3 describe pain along the maxillary division ( infraorbital nerve and anterior superior alveolar nerves) ( Fig. 2) ( 18,19). All have obvious trigger points and also suffer from referred pain resembling tic douloureux. This probably occurs because of ephaptic transmission, which is a cause of a more diffuse headache symptomatology ( 20). Each of the three patients reported a history consistent with prior trauma or inflammation to a branch of the trigeminal nerve. Patient 1 might have incurred damage to his infraorbital nerve during a retrobulbar block. Patient 2 suffers from trochleitis, which is known to be associated with rheumatoid arthritis ( 21). In trochleitis, the trochlear apparatus, which is a cartilaginous structure, becomes inflamed. This inflammatory process is not always associated with double vision. Patient 3 underwent significant dental work in the past, which might have resulted in local nerve damage. Whether Paget's disease in this patient is contributory remains unclear. Our patients were treated twice a day for 1 month and were then allowed to taper their dose as tolerated. Patient 1 was able to discontinue treatment after 1 year without recurrence of pain. Patient 2 improved on a reduced schedule, and patient 3 maintains improvement on capsaicin twice a day. Subjectively, discontinuation of the cream by patients 2 and 3 leads to a noticeable increase in symptoms within 2 weeks. The effect of capsaicin has been ascribed to its capacity to reduce the level of substance P in sensory fibers ( type- C nociceptors). Because this drug is specific for type- C neurons, it affects only sensory pain transmission and not the transmission of touch, pressure, or vibration ( 3- 6). Though capsaicin depletes substance P from synaptic vesicles in the terminal endings of sensory neurons, it does not cause permanent alteration in function; upon discontinuation of the cream, the sensory neurons return to their baseline state ( 22). This probably explains why all three patients noted at least one recurrence during tapering or following discontinuation of the drug. It is unclear what frequency of application is needed to achieve the optimal therapeutic effect; we chose a twice-a- day schedule of 15 mg to encourage compliance. Because capsaicin is from the pepper family, ocular exposure causes a transient burning sensation, but does not cause any damage. Patients are instructed to wash their hands with soap and water before and after applying capsaicin. They are asked to use a cotton cloth or cotton ball to wipe clean the area of treatment ( wiping in a direction away from their eyes) prior to washing of the face. The only side effect noted by the three patients was a burning sensation at the site of application, which decreased with continued application of the cream. All three patients noted cessation of the burning within 10 FIG. 2. Peripheral nerve endings of the trigeminal system: infraorbital nerve, infratrochlear nerve, and anterior superior alveolar nerves. J Neuw- Ophllwlmol, Vol. 18, No. I, 1998 20 N. S. 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