Orofacial pain management: An update

MARTORELL-CALATAYUD L, GARCÍA-MIRA B, PEÑARROCHA-DIAGO M. OROFACIAL PAIN MANAGEMENT: AN UPDATE. MED ORAL 2004;9:293-9.

SUMMARY

New treatments for orofacial pain have been developed in recent years. In the case of cluster headache, new drugs are now administered via the intranasal route, while in patients with chewing pain the topical application of capsaicin and the use of oral splints in combination with jaw movement exercises are the most widely used management approaches. In the case of neurogenic pain new anticonvulsivants have been introduced, with fewer side effects than carbamazepine. The latest pharmacological advances involve the use of nonsteroidal antiinflammatory drugs and opioids via the topical route, and the combination of different analgesics. The present review discusses the latest advances in the treatment of orofacial pain.

Key words: Orofacial pain, vascular pain, chewing pain, neurogenic pain.

INTRODUCTION

A review is made of the most important articles on advances in the management of orofacial pain published in the literature between 1998 and 2002, based on a Medline search and evaluation of the different Spanish dental journals.

1.-LOCAL OROFACIAL PAIN: MUCOSA, DENTAL AND GLANDULAR

In situations of oral tissue infection, antibiotics provide pain relief by reducing the inflammation (1). However, in cases of irreversible pulpitis, penicillin does not diminish pain, and endodontics is the treatment of choice (2).

Pain in endodontic treatment may develop following root canal instrumentation, as a result of acute periodontal tissue inflammation. Triamcinolone acetonide is a potent corticosteroid that can be used to eliminate or reduce severe inflammation secondary to endodontic treatment. The use of antibiotic-corticosteroid gel applied to the interior of the root canal reduces pain in the first hour in most patients, without adverse effects or recurrences (3).

In orofacial pain secondary to glandular obstruction, radiology (4), endoscopy (5,6) and ultrasound (7) allow identification of the obstruction and evaluation of the glandular alterations; removal of the culprit calculus or dilatation of the stenotic point will relieve duct pressure and eliminate the pain (8).

2.-VASCULAR PAIN

Peñarrocha and Bagán (9) reviewed the diagnostic criteria, differential diagnosis and treatment of autonomic trigeminal headaches. In cluster headache, sumatriptan is used via the subcutaneous route during the acute phase (10-13). Administration of the drug via the intranasal route has recently been introduced (14). Capsaicin has been administered as prophylaxis, though the side effects of this drug led to the adoption of a derivative (civamide), administered once a day for 7 days in the nostril homolateral to the pain - with a significant reduction in the number of pain episodes (15). Likewise, other drugs have been introduced in recent years as background treatment, such as verapamil, corticosteroids, valproic acid, serotonin inhibitors (11,12), topiramate (16) and naratriptan (17).

Indomethacin is the treatment of choice in patients with paroxysmal hemicrania, where it affords total pain remission (10). In hemicrania continua good results are also obtained with indomethacin (9,18). Pareja et al. (18), during an average follow-up of 3.8 years of a series of 26 patients treated with indomethacin, reported a reduction of over 60% in pain in 42% of the subjects. Other drugs such as the selective cyclooxygenase-2 (COX) inhibitors have also been employed. Peres et al. (19) used celecoxib and rofecoxib to treat 14 patents (5 and 9 subjects, respectively) with hemicrania continua. Symptoms remission was observed in three cases in each group.

SUNCT (short-lasting unilateral neuralgiform headache wit con-junctival injection and tearing) is resistant to indometacina, suma-triptan and amitriptyline (20), though remissions have been reported with carbamazepine and corticoids. In application to this type of headache new antiepileptic substances such as lamotrigine (20), gabapentin, and topiramate have also been used (21). D'Andrea et al. (20) in 5 patients diagnosed with SUNCT refractory to carbamazepine, administered lamotrigine at an initial dosage of 25 mg/day, followed by gradual increments to a maximum of 125-200 mg/day. As a result, the pain subsided in three of them and almost completely disappeared in two patients.

3.-CHEWING PAIN

The topical treatment of pain in the region of the temporomandibular joint (TMJ) with capsaicin is as effective as placebo - with 50% reductions in pain in both cases (after a period of four weeks)(22).

The oral administration of glycosamine and chondroitin sulfate is effective and safe for reducing the symptoms of TMJ osteoarthritis. A daily dose of 1500 mg of glycosamine hydrochloride combined with 1200 mg of chondroitin sulfate, for 12 weeks, reduces TMJ laxity, joint sounds and the number of analgesics required in patients with TMJ pain (23).

The use of oral acrylic splints exerts a moderate effect upon myofascial pain (24). A combination of mandibular mobilization exercises, manual distraction of the joint junction, mobilization of the condyle-disc complex, the correction of body posture, and relaxation techniques contribute to provide significant pain relief. This combination seems to be effective for the treatment of TMJ osteoarthritis symptoms (25). Such reduction in TMJ pain and dysfunction is achieved after several weeks of domiciliary controlled neuromuscular exercises (26).

4.-NEUROGENIC PAIN

-Medical management

Carbamazepine is still used for the treatment of trigeminal neuralgia (27-29). According to Reisner et al. (29), in a review of the use of anticonvulsivants for the treatment of orofacial pain, lamotrigine, gabapentin, oxcarbazepine, tiagabin and topiramate are all as effective as carbamazepine, though with the added advantage of causing fewer side effects (30-32). In the event pain fails to respond to carbamazepine, phenytoin could be the drug of second choice. If the presence of side effects limits the use of anticonvulsivants, baclofen (a gamma-aminobutyric acid agonist and muscle relaxant) could be used.

Delvaux et al. (30) administered lamotrigine to 25 patients diagnosed with trigeminal neuralgia, atypical pain facial, migraine, cluster headache and chronic tensional headache. The doses administered were progressive from 25 mg/day to the effective dosage (250 mg/day on average). After 18 months of follow-up, lamotrigine was seen to be more effective for the management of trigeminal neuralgia than in application to the rest of facial pain disorders.

Fischoff and Sirois (33) administered gabapentin to a patient with multiple sclerosis associated to trigeminal neuralgia. A dose of 2700 mg/day was required - tolerance being good, with the absence of pain in the two years of follow-up. Rowbotham et al. (34) administered gabapentin for 8 weeks at incremental doses to 3600 mg/day in 109 patients with postherpetic neuralgia, with pain reduction in 33% of the patients versus 7.7% of the controls.

Topical drugs have been applied for the treatment of neurogenic trigeminal pain (35,36). Epstein et al. (35), in a study of 7 patients, applied clonidine (an adrenergic agonist) in cream form at a concentration of 0.2 mg/g, four times a day. Fifty-seven percent of the patients improved (with pain reduction by over 50%). According to Padilla et al. (36), capsaicin (which stimulates the release of substance P and other neurotransmitter peptides) is effective when applied topically at doses of 0.025% and 0.075%.

-Surgery and radiotherapy

Neurosurgery

Pollock et al. (37), subjected 68 patients with trigeminal neuralgia refractory to pharmacological treatment to irradiation (70 or 90 Gy) using the Model B Leksell gamma knife system. The pain disappeared in 41% of the cases with low-dose irradiation, and in 61% with the high dose. The authors recommended the delivery of doses of under 90 Gy to avoid side effects such as permanent trigeminal nerve dysfunction and paresthesias.

Tyler-Kabara (38) performed intracranial microvascular decompression in a total of 2003 patients with typical trigeminal neuralgia, and in 673 subjects with atypical neuralgia. Eighty percent of the patients experienced complete pain resolution in the immediate postoperative period, and 73% maintained such improvement over the long term (more than 5 years).

5.-BONE PAIN

Bouquot and McMahon (39) amplified the term alveolar osteopathy, defining it as edema of the bone marrow, caused by vascular alterations that entail bone thrombosis and microinfarction. Treatment consists of complete resection of the bony tissue corresponding to the painful zone, identified following anesthetic block (39-41). Following extraction of the bone fragment, the marrow is subjected to curettage. After culture and an antibiogram, the authors applied an antibiotic to the zone, to increase the drug concentration in the area and reduce the incidence of side effects. This procedure has also been carried out with the help of hyperbaric oxygen (41).

Bouquot and McMahon (39) viewed cavitary alveolar osteopathy in the same way as any other disorder of the oral cavity, and in future special attention will have to focus on the dangerous potential prothrombotic effects in these patients. Knowledge in the field of imaging techniques should be expanded, and interest should focus on the systemic and local effects of alveolar infections and necrotic processes. To date, no uniform diagnostic or management criteria have been defined (40).

6.-POSTOPERATIVE PAIN

Deficient oral hygiene is associated with increased pain following lower molar surgery, and thus with a greater use of analgesics. Preoperative mouthrinses with chlorhexidine reduce the incidence of dry socket in simple extractions and in lower third molar surgery (42).

The latest studies focus on the topical application of opioids and NSAIDs, to avoid the side effects associated with systemic dosing (43), and on the combination of analgesics in order to reduce the individual doses and thus limit adverse effects (44).

-Nonsteroidal antiinflammatory drugs (NSAIDs)

Paracetamol at a dose of 1 g as single therapy or in combination with 60 mg of codeine has been shown to be effective for the treatment of pain after oral surgery (44). Codeine at a dose of more than 60 mg implies a significant increase in adverse effects, without concomitant improvement in analgesia (45). In the case of more intense pain it is advisable to combine 1 g of paracetamol with 10 mg of oxycodone (44). The use of NSAIDs and steroidal antiinflammatory drugs in the pre- and intraoperative phases is beneficial in terms of pain reduction and swelling after the operation (46).

Certain cytokines have been related to tissue damage, including IL-1b, whose pharmacological reduction with ibuprofen affords a reduction in pain (46). A dose of 400 mg of this drug every 8 hours leads to a reduction in postoperative pain in 65% of the patients subjected to dentoalveolar surgery (47). NSAIDs require higher doses in order to achieve adequate antiinflammatory effects compared with the dosage needed to afford good analgesia. In the case of ibuprofen, 2400-3200 mg/day are needed to achieve antiinflammatory action, while analgesia is provided by 200-600 mg 4 four times a day, or 800 mg three times a day (44).

Ketorolac with codeine also achieves adequate pain control after the extraction of impacted lower molars. The best results are obtained by combining 10 mg of ketorolac and 15 mg of codeine phosphate. In this way the amount of codeine required for pain relief is reduced (along with its adverse effects)(48).

Ketorolac and tramadol show similar postoperative analgesic performance, significant differences between the two drugs being limited to their respective side effects (49). No differences are observed between doses of 10 and 20 mg of ketorolac in the treatment of postoperative pain - efficacy being superior to that of 50 mg of ketoprofen (50).

Two specific cyclooxygenase-2 inhibitors (COXIBS), celecoxib and rofecoxib, have been introduced, with an efficacy similar to that of naproxen, ibuprofen, diclofenac and acetylsalicylic acid (aspirin) for the treatment of dental pain. Rofecoxib induces analgesia comparable to that afforded by other NSAIDs (such as ibuprofen 400 mg)(51), though the duration of the effect exceeds 24 hours after a single dose, and is not associated with gastrointestinal adverse effects. The duration of action in the case of celecoxib is similar to that of rofecoxib, though its analgesic potential is slightly less (52). Both drugs allow convenient dosing (1-2 daily doses)(51). A single dose of 50 mg of rofecoxib affords greater analgesia, a faster onset of analgesic action, and a longer-lasting effect than a single dose of 50 mg of diclofenac in patients with pain associated to lower molar surgery (53). However, since little is yet known of the long-term effects of the COXIBS, it is advisable to limit their use to patients with a risk of developing severe gastrointestinal complications due to NSAIDs, and when chronic pain is involved (54,55). Although rofecoxib is more expensive than other NSAIDs, it is less expensive than the sum of the cost of these latter drugs plus the addition of a gastroprotective agent such as omeprazole (54).

- Other drugs

The administration of an opioid or a local anesthetic prior to surgical intervention postpones the onset of pain. The efficacy of the local anesthetic administered before or after surgery is the same - provided it is applied before pain develops (56).

Fentanyl (an opioid) injected in combination with anesthetics such as mepivacaine, increases and prolongs the anesthetic effect in inflammatory zones. This in turn implies a lesser need for postsurgical analgesic measures (57).

Intranasal tartrate butorphanol (Stadol NS^®), a synthetic analgesic-opioid agonist-antagonist, offers great efficacy and safety in controlling pain after third molar extraction. It is moreover easy to administer, the analgesic effect is rapid, and administration is possible when the patient has difficulties swallowing. This medication affords 50% pain reduction within 15 minutes after the first dose, and the effect lasts about four hours. Ladov et al. (58) suggested the use of intranasal Stadol NS^® as first choice pharmacological treatment of pain after third molar extractions and oral surgery in general. Desjardins et al. (59) recommended a dose of 1.0 mg with the purpose of reducing the adverse effects.

(Note: for the prescription of these drugs, consult the dosage with the specific indications for each product as specified by the manufacturing laboratory)

REFERENCES

1. Sanz M, Herrera D, Martínez A, López JL, Aguirre JM, García MJ, et al. Estudio clínico comparativo de la eficacia de azitromicina frente a amoxicilina / ac. clavulánico en el tratamiento de infecciones orales agudas. RCOE 2001;6:387-94.        [ Links ]

2. Nagle D, Reader A, Beck M, Weaver J. Effect of systemic penicillin on pain in untreated irreversible pulpitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:636-40.        [ Links ]

3. Negm MM. Intracanal use of a corticosteroid-antibiotic compound for the management of posttreatment endodontic pain. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:435-9.        [ Links ]

4. Salerno S, Cannizzaro F, Lo Casto A, Lombardo F, Barresi B, Speciale R, et al. Interventional treatment of sialolithiasis in main salivary glands. Radio Med 2002; 103:378-83.        [ Links ]

5. Nahlieli O, Baruchin AM. Long term experience with endoscopic diagnosis and treatment of salivary gland inflammatory diseases. Laryngoscope 2000;110:988-93.        [ Links ]

6. Marchal F, Dulguerov P, Becker M, Barki G, Disant F, Lehmann W. Submandibular diagnostic and interventional sialendoscopy: new procedure for ductal disorders. Ann Otol Rhinol Laryngol 2002;11:27-35.         [ Links ]

7. Zenk J, Constantinidis J, Al- Kadah B, Iro H. Transoral removal of submandibular stones. Arch Otolaryngol Head Neck Surg 2001;127:432-6.        [ Links ]

8. Drage NA, Brown JE, Escudier MP, Wilson RF, McGurk M. Balloon Dilatation of Salivary Duct Strictures: Report on 36 Treated Glands. Cardiovasc Intervent Radiol 2002;25.        [ Links ]

9. Peñarrocha M, Bagán JV. Cefaleas trigeminales autonómicas. Medicina Oral 2000;5:96-108.        [ Links ]

10. Benoliel R, Sharav Y. Paroxismal hemicrania. Case studies and review if the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998;85:285-92.        [ Links ]

11. Pradalier A, Baudesson G, Vincent D, Imberty-Campions C. Treatment of cluster headache. Rev Med Interne 2001;22:151-62.        [ Links ]

12. Ekbom K, Hardebo JE. Cluster headache: aetiology, diagnosis and management. Drugs 2002;62:61-9.        [ Links ]

13. Matharu MS, Goadsby PJ. Persistence of attacks of cluster headache after trigeminal nerve root section. Brain 2002;125:976-84.        [ Links ]

14. Schuh-Hofer S, Reuter U, Kinze S, Einhaupl KM, Arnold G. Treatment of acute cluster headache with 20 mg sumatriptan nasal spray—an open pilot study. J Neurol. 2002;249:94-9.        [ Links ]

15. Saper JR, Klapper J, Mathew NT, Rapoport A, Phillips SB, Bernstein JE, for the intranasal Civamide Study Group. Intranasal civamide for the treatment of episodic cluster headaches. Arch Neurol 2002;59:990-4.        [ Links ]

16. Foderreuther S, Mayer M, Straube A. Treatment of cluster headache with topiramate: effects and side-effects in five patients. Cephalalgia 2002;22:186-9.        [ Links ]

17. Loder E. Naratriptan in the prophilaxys of cluster headache. Headache 2002;42:56-7.        [ Links ]

18. Pareja JA, Caminero AB, Franco E, Casado JL, Pascual J, Sanchez del rio M. Dose . Efficacy and tolerability of long term indomethacin treatment of chronic paroxysmal hemicrania and hemicrania continua. Cephalalgia 2001;21:906-10.        [ Links ]

19. Peres MF, Silberstein SD. Hemicrania continua responds to cyclooxygenase-2 inhibitors. Headache. 2002;42:530-1.        [ Links ]

20. D’Andrea G, Granella F, Ghiotto N, Nappi G. Lamotrigine in the treatment of SUNCT syndrome. Neurology 2001;57:1723-5.        [ Links ]

21. Matharu MS, Boes CJ, Goadsby PJ. SUNCT syndrome: prolonged attacks, refractoriness and response to topiramate. Neurology 2002;58:1307.        [ Links ]

22. Winocur E, Gavish A, Halachmi M, Eli I, Gazit E. Topical application of capsaicin for the treatment of localized pain in the temporomandibular joint area. J Orofac Pain 2000;14:31-6.        [ Links ]

23. Nguyen P, Mohamed SE, Gardiner D, Salinas T. A randomized double-blind clinical trial of the effect of chondroitin sulfate and glucosamine hydrochloride on temporomandibular joint disorders: A pilot study. Cranio 2001;19:130-9.        [ Links ]

24. Raphael KG, Marbach JJ. Widespread pain and the effectiveness of oral splints in myofascial face pain. J Am Dent Assoc 2001;132:305-16.        [ Links ]

25. Nicolakis P, Burak EC, Kollmitzer J, Kopf A, Piehslinger E, Wiesinger F, et al. An investigation of the effectiveness of exercise and manual therapy in treating symptoms of TMJ osteoarthritis. Cranio 2001;19:26-32.        [ Links ]

26. Zeno E, Griffin J, Boyd C, Oladehin A, Kasser R. The effects of a home exercise program on pain and perceived dysfunction in a woman with TMD: A case study. Cranio 2001;19:279-88.        [ Links ]

27. Rancurel G. Algies de la face non dentaires. Le point de vue du neurologue. Actualités Odonto Stomatologiques 2000;209:103-12.        [ Links ]

28. Peñarrocha M, Peñarrocha MA, Soler F, Bagán JV. Neuralgia trigeminal secundaria a dolicoectasia de la arteria basilar. Medicina Oral 2001;6:36-9.        [ Links ]

29. Reisner L, Pettengill CA. The use of anticonvulsivants in orofacial pain.Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;91:2-7.        [ Links ]

30. Delvaux V, Schoenen J. New generation anti epileptics for facial pain and headache. Acta Neurol Belg 2001;101:42-6.        [ Links ]

31. Zakrzewska JM, Patsalos PN. Long-term cohort study comparing medical (oxcarbazepine) and surgical management of intractable trigeminal neuralgia. Pain 2002;95:259-66.        [ Links ]

32. Serpell MG. Neuropathic Pain Study Group. Gabapentin in neuropathic pain syndromes: a randomised, double blind, placebo controlled trial. Pain 2002;99:557-66.        [ Links ]

33. Krimsky Fischoff D, Sirois D. Painful trigeminal neurophathy caused by severe mandibular resorption and nerve compression in a patient with systemic sclerosis: case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000;90:456-9.        [ Links ]

34. Rowbotham M, Harden N, Stacey B, Bernstain P, Magnus-Miller L. Gabapentin for the treatment of postherpetic neuralgia. JAMA 1998;280:1837-42.        [ Links ]

35. Epstein JB, Grushka M, Nhu L. Topical clonidine for orofacial Pain: a pilot study. J Orofac Pain 1997;11:346-52.        [ Links ]

36. Padilla M, Clark GT, Merrill RL. Topical medication for neuropathic pain: a review. J Am Dent Assoc 2000;131:184-95.        [ Links ]

37. Pollock BE, Phuong LK, Foote RL, Stafford SL, Gorman DA. High dose trigeminal neuralgia radiosurgery associated with increased risk of trigeminal nerve dysfunction. Neurosurgery 2001;49:58-62.        [ Links ]

38. Tyler-Kabara EC, Kassam AB, Horowitz MH, Urgo L, Hadjipanayis C, Levy EI, et al. Predictors of outcome in surgically managed patients with typical and atypical trigeminal neuralgia: comparison of results following microvascular decompression. J Neurosurg 2002;96:527-31.        [ Links ]

39. Bouquot JE, McMahon RE. Neuropathic pain in maxillofacial osteonecrosis. J Oral Maxillofac Surg 2000;58:1003-20.        [ Links ]

40. Zuniga JR. Challenging the neuralgia-inducing cavitational osteonecrosis concept. J Oral Maxillofac Surg 2000;58:1021-8.        [ Links ]

41. Carmony B, Bobbitt TD, Rafetto L, Cooper EP. Recurrent mandibular pain and swelling in a 37-year-old man. J Oral Maxillofac Surg 2000;58:1029-33.        [ Links ]

42. Peñarrocha M, Sanchis JM, Sáez U, Gay C, Bagán JV. Oral hygiene and postoperative pain after mandibular third molar surgery. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:260-4.        [ Links ]

43. Swift JQ. Nonsteroidal anti-inflamatory drugs and opioids: Safety and usage concerns in the differential treatment of postoperative orofacial pain. J Oral Maxillofac Surg 2000;58:8-11.        [ Links ]

44. Mehlisch DR. The efficacy of combination analgesic therapy in relieving dental pain. J Am Dent Assoc 2002;133:861-71.        [ Links ]

45. Ziccardi VB, Desjardins PJ, Daly-Dejoy E, Seng GF. Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions. Int J Oral Maxillofac Surg 2000;58:622-8.        [ Links ]

46. Reebye UN. Efficacy of anti-inflamatory drugs in the reduction of IL-1_ in third molar surgery. Int J Oral Maxillofac Surg 2000;58:75-6.        [ Links ]

47. Joshi A, Snowdon AT, Rood JP, Worthington HV. Pain control after routine dento-alveolar day surgery: a patient satisfaction survey. Br Dent J 2000;189:439-42.        [ Links ]

48. Garibaldi JA, Elder MF. Evaluation of ketorolac (Toradol)® with varying amounts of codeine for postoperative extraction pain control. Int J Oral Maxillofac Surg 2002;31:276-80.        [ Links ]

49. Zackova M, Taddei S, Calo P, Bellocchio A, Zanello M. Ketorolac vs tramadol in the treatment of postoperative pain during maxillofacial surgery. Minerva Anestesiol 2001;67:641-6.        [ Links ]

50. Olmedo MV, Galvez R, Vallecillo M. Double-blind parallel comparison of multiple doses of ketorolac, ketoprofen and placebo administered orally to patients with postoperative dental pain. Pain 2001;90:135-41.        [ Links ]

51. Moore PA, Hersh EV. Celecoxib and rofecoxib-the role of COX-2 inhibitors in dental practice. J Am Dent Assoc 2001;132:451-6.        [ Links ]

52. May N, Epstein J, Osborne B. Selective COX-2 inhibitors: A review of their therapeutic potential and safety in dentistry. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2001;92:399-405.        [ Links ]

53. Chang DJ, Desjardins PJ, Chen E, Polis AB, McAvoy M, Mockoviak SH, et al. Comparison of the analgesic efficacy of rofecoxib and enteric-coated diclofenac sodium in the treatment of postoperative dental pain: a randomized, placebo-controlled clinical trial. Clin Ther 2002;24:490-503.        [ Links ]

54. Salido M, Abásolo L, Bañares A. Revisión de los antiinflamatorios inhibidores selectivos de la ciclooxigenasa-2. Inf Ter Sist Nac Salud 2001;25:46-52        [ Links ]

55. Jeske AH. Selecting new drugs for pain control. Evidence-based decisions or clinical impressions? J Am Dent Assoc 2002;133:1052-6.        [ Links ]

56. Dionne RA. Pharmacologic advances in orofacial pain: From molecules to medicine. J Dent Educ 2001;65:1393-403.        [ Links ]

57. Anderson PE. Anesthetic and analgesic effects of locally administered fentanyl in inflamed dental models. Int J Oral Maxillofac Surg 2000;58:74-5.        [ Links ]

58. Ladov MJ, Precheur HV, Rauch DM, Engel PS, Stern RK. An open-label evaluation of the efficacy and safety of stadol NS with ibuprofen in the treatment of pain after removal of impacted wisdom teeth. J Oral Maxillofac Surg 2000;58:15-8.        [ Links ]

59. Desjardins PJ, Norris LH, Cooper SA, Reynolds DC. Analgesic efficacy of intranasall butorphanol (Stadol NS) in the treatment of pain after dental impaction surgery. J Oral Maxillofac Surg 2000;58:19-26.        [ Links ]