|CONTINUING MEDICAL EDUCATION
|Year : 2002 | Volume
| Issue : 3 | Page : 123-130
Cutaneous and mucosal pain syndromes
"Parakruthi", 2830, 4th Main, M. C. Colony, 'B' Block, Davangere-577 044. Karnataka State, India
"Parakruthi", 2830, 4th Main, M. C. Colony, 'B' Block, Davangere-577 044. Karnataka State, India
The cutaneous and mucosal pain syndromes are characterized by pain, burning sensation, numbness or paraesthesia of a particular part of the skin or mucosal surface without any visible signs. They are usually sensory disorders, sometimes with a great deal of psychologic overlay. In this article various conditions have been listed and are described. The possible causative mechanisms are discussed when they are applicable and the outline of their management is described.
|How to cite this article:|
Siddappa K. Cutaneous and mucosal pain syndromes. Indian J Dermatol Venereol Leprol 2002;68:123-30
Many of us have encountered Patients with cutaneous and mucosal pain syndromes. Because of no visible signs, these patients move from specialist to specialist in search of relief for their symptoms. They look to the dermatologists as the symptoms involve the skin and the adjoining mucous membranes.
As dermatologists, we must try to know about these conditions to deal with these patients.
| What are these conditions?|| |
The cutaneous and mucosal pain syndromes are characterized by pain, burning sensation, numbness or paraesthesia of a particular part of the skin or mucosal surface. They are usually sensory disorders, sometimes with a great deal of psychologic overlay. They could be possibly linked by some unknown common denominator likely a peripheral and/or central dysfunction of afferent nerve fibers.
| Which are these conditions?|| |
1. Notalgia paraesthetica
2. Brachioradial pruritus
3. Skin-ache syndrome
4. Chronic skin pain
5. Atypical facial pain
6. Syndrome of oral cimplaints.
7. Burning mouth syndrome
9. perianal pain syndrome
10. Scrotodynia, penilodynia
11. Chronic perianal pain and "perianal syndrome"
12. Prostatodynia, scalpodynia
13. Even intractable pruritus ani, vulvae and scrotum may be a vatiant of these chronic pain disorders.
| Conditions:|| |
| 1. Notalgia paraesthetica (NP)|| |
This unique Pain syndrome was first described in 1934. It is characterized by episodes of localized itching or burning pain in the midscapular area. Initially starting as a unilateral prurtus close to the medial border of the scapula, can progress to distressing burning pain in the region and often extending from there to a more widespread distribution including the scalp., In most cases it probably arises as the consequence of an isolated sensory neuropathy. Although popularly believed to be a rare condition, in its milder form it appears to be quite common. It has been even described in multiple family members and reported in association with multiple endocrine neoplasia type 2a and macular amyloidosis.
Etiology and pathogenesis
Although the cause is not known, there is some electromyographic evidence to support the theory that it is an isolated peripheral sensory neuropathy affecting spinal nerves in the T-2 to Tb region. According to Massey and Pleet the spinal nerves arising at these levels emerge at right angles through the multifidus spinae muscle and may be exposed to harm from otherwise innocuous insults such as back trauma. Neutopeptides may play a role in the pathophysiology of this condition in view of the therapeutic success of capsaicin.
There are no specific primary changes in the skin. But features of lichenification and postinflammotory pigmentary changes apparently due to trauma induced melanin within the macrophages may be detected in some longstanding cases. Other changes observed included necrotic keratinocytes in the epidermis, proliferation of substance-P immunoreative nerve endings and increased cutaneous innervation which may represent nonspecific change and features of macular amyloidosis in some cases: keratin derived amyloid deposition may be the consequence of repetitive scratching or friction.,
The patient cimplains of itching in the midscapular region, usually localized to one side or the other. Tingling, burning, formication, hyperalgisia and even tenderness may be present. There are no visible cutaneous changes in most of the cases but in some long standing cases secondary changes such as lichenification, hype rpigmentation and amyloid deposition may develop due to rubbing or scratching.,
Diagnosis is usually based on the characteristic complaint of itching or related symptoms localised to the upper back, usually to one side or the other of the mid line.
| 2. Brachioradial pruritus|| |
This is a sunlight-induced chronic pruritus characterized by an intermittently burning itch localized to the bilateral outer aspects of the elbow and adjacent lower and upper arms-C6 to C8 area. There is cutaneous hyperaesthesia in the area. The condition is commoner in faircoloured persons living in tropical climates and rare in temperate climates. Atypical female patient who had spent much of the year sailing and golfing in the Carribean region responded to the treatment by topical capsaicin cream.
Pruritus due to chronic sun exposure may occasionally be much more widespread and has been termed 'solar pruritus'. It is probably identical to brachioradial pruritus.
| 3. Skin-ache syndrome|| |
In skin-ache syndrome, patients experience pain of unknown aetiology characterized by cutaneous trigger points. Relief of symptoms is reported after injection of lidocaine or surgical removal of the skin trigger point.
| 4. Chronic skin pain|| |
The diagnosis of dysmorphophobia or dermatological non-disease should always be condidered when patients present with chronic skin pain (especially when areas important to body image are involved). These include burning vulva syndrome (vulvodynia), and burning scrotum syndrome (scrotodynia) as well as orodynia. However other entities including notalgia paraesthetica, skin-ache syndrome and postherpetic neuralgia should also be kept in mind.,
| 5. Atypical facial pain (AFP)|| |
There are several psychogenic types of orofacial pain, and in some population studies nearly 40% of people have reported frequent headache and facial pain., It is an ill-defined entity which includes atypical facial pain (or neuralgia), atypical adontalgia and the 'syndrome of oral cimplaints'.
In atypical facial pain patients, who are often middle aged or elderly females, complain of constant chronic discomfort or pain-dull, boring or burning type and not localized to any specific site. Patients who suffer from psychogenic pain appear to belong to four main groups: (a) normal individuals under extreme stress; (b) those with a personality trait such as hypochondriasis; (c) neurotic often depressed persons, and (d) psychotic patients.
There is a total lack of objective signs, and cure is uncommon.
| 6. The syndrome of oral complaints|| |
Multiple type of pains and other complaints (such as dry mouth or disturbed taste) may occur simultaneously or sequentially, and relief is rarely found.,
| 7. Burning mouth syndrome (BMS)|| |
(synonyms: glossodynia, glassopyrosis, orodynia, burning tongue, hot tongue syndrome and oral dysesthesia).
Oral musosa usually burns but rarely itches. Burning sensation of oral mucosa occurs in a variety of oral conditions, but the burning mouth syndrome is an intraoral pain disorder and irritation of mucosal origin that is unaccompained by clinical signs., Therefore it is essentially diagnosed by rulingout other possible causes.
The numerous causes which have been suggested to produce burning mouth include.
1. Systemic causes
(a) Nutritional dificiencies
- Vitamin B Deficiencies
- Folate deficiency
- Zinc deficiency
- Iron deficiency
- Vit. B12 deficiency
(c) Thyroid disorders
(d) Menopausal (postmenopausal (hypoestrogenism)
(f) Drug therapy (antibiotic)
(g) Temporal arteritis
2. Local causes
(a) Candidial infection
(b) Infection by coliform species Enterobacter and klebsiella species)
(c) Fusospirochetal infection (in edentulous patients)
(d) Denture microtrauma to oral mucosa
(e) Mouth wash use
(f) A variety of irritants that may cause microtrauma to the oral mucosa.
(g) Oesophagial reflux
(h) 'Busy' tongue
(j) Periodontal disease
(k) Referred pain (apical abscess)
(l) Stomatitis medicamentosa
3. Misellaneous causes
(b) Sensory neuropathies
4. Idiopathic Aetiology
The cause is unclear. The disorder may be considered as secondary to psychologic disturbance or idiopathic in many patients. In large number of patients psychological aspects such as anxiety, depression and neurotic tendencies are of great importance. Two studies conducted by Gorsky and his colleagues have indicated that the BMS may be a functional disorder. Another study by Rhodus and colleagues has demonstrated significantly elevated levels of substance-P, a potentially neurogenic source of chronic pain. The finding of these data indicate that BMS patients have significantly decreased serotonin, estrogen and progesterone levels. In view of recent evidence, BMS may be associated with damage to the chorda tympani with loss of central inhibition of the trigeminal nerve. A painful burning tongue may develop during temporal arteritis or be the initial presenting symptom. Burning symptoms in the mouth may of cource be a manifestation of hysteria in neurotic patient. Galvanism (the phenomenon of electrochemical currents between different metal restorations with the saliva acting as a conductor) is also hypothesized as a possible cause.
Although its prevalence is uncertain, it has been reported worldwide, and it mostly affects peri and postmenopausal women. Onset is gradual in majority of the patients and sudden in minority of the patients.
Patients complain either of burning on waking which persists throughout the day or develop burning the day, worsening as the day goes on. Whole of the oral cavity can be affected, but the burning occurs most frequently in the distal structures of the mouth, affecting the tongue predominantly. It is usually bilateral and often is relieved by eating and drinking. There is a significant decrease in pain tolerance of oral mucosa to noxious stimuli in BMS., The associated symptoms include dry mouth, persistent taste, altered eating habits, thirst, difficulty in swallowing, other throat problems, altered smell, sleep distrurbances, mood changes, dry eyes, swollen face/cheeks, pain complaints, nonspecific health problems and severe menopausal complaints.,,
Immunological abnormalities and elevated ESR appear to be more in BMS patients.
On oral examination the tissues appear clinically normal.
| 8. Vulvodynia|| |
(Odynia-a Greek term for pain, localised discomfort).
The complaint of burning seems more common on mucous membranes than on keratinized epithelium and pruritus is reported to occur more frequently on gential mucosa than on oral mucosa.
Chronic gential pain, burning or the sensation of irritation in the absence of obvious physical findings is an occasional but debilitating syndrome. Vulvodynia (burning of the vulva) is far more common that scrotodynia or penile pain. Complaints of vulval pain are becoming much more common. The term 'vulvodynia' has been applied to a group of symtoms characterized by chronic and often unremitting pain, burning, stinging or rawness of the vulval area. Pruritus is absent. Examination shows neither signs of primary disease nor secondary changes associated with rubbing or scratching.,, Adult age groups are involved and many patients will indicate the precise localization of symtoms. Vulvodynia is ofen multifactorial. Vast majority of women are extremely depressed and experience major disruption in their sexual functioning., It is generally not belived to result primarily from psychosexual dysfuction. Since the cause of this syndrome is unknown, treatment is empirical and should be as conservative as possible.
There are four subtypes of vulvodynia.
(a) Cyclic vulvovaginitis (cyclic vulvitis-CV)
Episodic vulvodynia with freedom from symtoms between recurrences is typical of cyclic vulvovaginitis. It is characterized by intermittent pruritus and burning that may be associated with erythema or the sensation of swelling. Symptoms vary with the menstrual cycle and are worsend after coitus. Usually seen in premenopausal woman or a woman on oestrogen replacement therapy. These patients have redness and inflammation at the introtus, and the skin splits easily, probably as a result of underlying oedema. Vaginal discharge is rare. There is history of frequent candidial infection and frequent use of antibiotics for sinus conditions, urinary tract infection or acne.
The speculation is that this condition may be associated with changes in the vaginal ecosystem, because many patients report recurrence of symptoms at the time of menses or after intercourse.
(b) Vulvar vestibulitis sysnrome (V V S)
The vestibule is the inner portion of the vulva. It extends from the hymenal ring laterally to Hart's line (the junction of the keratinized skin and mucosa) on the inner surface of the labia minora, anteriorly to and includes the frenulum of the clitoris and posteriorly down to and includes the fourchette. This marks the beginning of vulvavaginal mucous membrane. This is the only portion of the female genital tract that is derived from endoderm. It is covered with epithelium that is not keratinized, and has characteristics that lie between mucous membrane and skin. It has all the sensitivity of mucous membrane and little of the resistance of skin. Into this space open the major vestibular glands (Bartholins, skenes and periurethral) and minor vestibular glands, which may number a few to many.,
The term vulvar vestibulitis syndrome is applied to a constellation of symptoms and signs consisting of (1) pain on penile entry (introital dyspareunia), (2) findings confined to focal erythema within the vulvar vestibule, and (3) exquisite tenderness on light palpation of erythematous areas that involve and limited to the vulvar vestibule.
In those, who are not sexually active, complaints range from pain on touching the vulvar vesibule, to pain on tampon insertion, on prolonged sitting, on riding a bicycle, on crossing the legs or wearing tight jeans. Except for these activities, patients are asymptomatic. The pain of VVS is typically chronic and continuous. Clinical findings are meager and confine to the vulvar vestibule. There is always erythema. Vulvar vestibular syndrome is one of the recognized subsets of vulvodynia.
It is one of the most disabling sub type of vulvodynia and is the most dificult to treat. The term V V S must be reserved for those patients whose symptoms are more than 6 months duration. Pain is not spontaneous, it is elicited by pressure on the erythematous areas within the vulvar vestibule. In a study by Furlonge, et al 92% of patients had symptoms that persisted for more than 6 months and in 25% for more than 2 years.
Though the incidence is increasing recently, the exact prevalence is not known. In a study of a general gynecologic practice population, 15% of 210 patients fulfilled the criteria of VVS.
The cause of V V S is unknown. The great majority of cases are idiopathic. According to one recent theory the alkalineurine from dietary oxalate, is irritating the genital skin and inflames the vestibular glands. Hence the patients are advised to take low-oxalate diet (e.g; asparagus, chocolate and many green leafy vegetables) and to take calcium citrate to bind the dietary exalates. It has been found to be associated with sub-clinical HPV infection, chronic recurrent candidiasis and persistant alteration of vaginal PH above or below normal PH which varies from 4.0 to 4.5. and therapy for some of these conditions sometimes leads to amelioration of the symptoms. There are also some reports of development of V V S after the disappearance of acute vulvitis due to chemical therapeutic agents and after laser therapy. Many believe that this syndrome is a form of reflex sympathetic dystropy.
Patients who describe episodic vestibulitis with symptom free intervals, even if they are only occasional, have a better prognosis for recovery. Remissions have occured spontaneously and with conservative therapy.
| Pudendal neuralgia (PN)|| |
Unprovoked burning pain radiating from the vulva to the rest of the prineum, groin or thighs is typical of pudendal neuralgia. It is often accompanied by a deep aching component and with occasional paroxysms of severe lanciating pain.
Deep itching, formication, a painful burning sensation on light touch, discomfort or burning on movement of pubic hairs, postcoital dypareunia and a sensation of labial swelling are additional cimplaints. Dysuria and frequent clitoris pain, sciatica like pains, and radiation of pain to the perineal area may be experienced by some patients. In general their discomfort is aggravated during midcycle or just before the onset of their menstrual period, as well as by sitting and standing for periods of time.
There are no visible changes, except for mild erythema around the opening of vestibular glands.
Most patients are on the age group of 20-30 years, but the age of the patient can vary from the late teens to 70 years.
Sendory testing of the area may elict a multiplicity of responses and these sensory responess may vary from day to day. Though these sensory findings are not confined to strict dermatomes, they stay in the general area innervated by the pudendal nerve.
The cause is idiopathic in majority of cases. In rare cases it may be associated with recurrent HSV infection, and following trauma or surgical procedure. The similarity of the symptoms to those described for postherpetic neuralgia and diabetic neuropathy suggests neuropathic pain in the area innervated by the pudendal nerve (S-2 to S-5).
(c) Dysesthetic ("Essential") vulvodynia (DV)
The term dysesthetic vulvodynia suggests a simple descriptive term for non specific burning on a neurologic basis. It consists of constant displeasurable more diffuse burning of the vulva independent of touch. Usually older or postmenopausal women are involved. They often complain of urethral or rectal discomfort in addition to vulvar burning, who are rarely receiving oestrogen replacement. If they are sexually active, they seldom complain of dyspareunia. These patients describe awareness of a low-grade burning that is always present.
The proposed theory for this neuralogic problem is that the sensory nerves are damaged and there is altered central sensory processing. Many clinicians believe that this is also a neuropathic pain, but more often a manifestation of pudendal neuralgia.
| Perianal pain syndrome|| |
In several syndromes, such as levator syndrome, dyspareunia is also a problem. However, in none of the descriptions of these entities, there is any mention of sensory abnormalities.
| Scrotodynia, penilodynia|| |
Scrotum or penis, usually glans penis, burns often. Patients describe of significant erythema, but on examination there is very little inflammation. Because of the rarity of this condition (scrotodynia), it is poorly understood. There is very little published information regarding causes and therapy. Some experienced clinicians feel that it is usually a manifestation of psychosexual dysfunction.
Chronic perianal pain and the "perianal syndrome"
Sensations of pain without any evident organic cause localised to the anogential region have been described under a number of names.,
Proctalgia fugas, which affects young adult males, occurs chiefly at night in the form of a sudden cramp-like pain and resolves in a few minutes.
'Coccygodynia','descending perineum pain, and 'chronic idiopathic anal pain' affect chiefly females. Pain is dull and throbbing and is often precipitated by sitting. Treatment is disappointing.
Dermatologists sometimes may be confronted by a problem in which the patient cimplains of short-lived episodes of intense burning limited to perineum or occasionally scrotum, which may be accompanied by sweating. The attacks occur without any warning but sometimes may be brought about by a full rectum. The patients usually tends to be under stress and the skin is entirely normal in these conditions.
Mechanism is unknown. Cholinergic may be suggested because of relief from propantheline. The group may also fall into the group of 'dermatological non-diseases.
Similar condition has been reported in childern suffering from intrafamilial stresses.
When we begin wondering about these pain syndromes, we will hear and see other areas of the body involved as pain and itch sensation are carried on the same unmyelinated type C nerve fibers.
| How to manage these conditions?|| |
1. The first step in dealing with these patients is reassurance that their problem is not likely to be in their head and that there is a definable diagnosis.
2. Give them adequate time to tell you about the nature of their problem.
3. Treatment of any underlying or associated conditions if any. V V S is a condition whose exact cause is not known, and it may even be the final pathway of several causative agents. Therefore therapies directed at those conditions thought to playa role in the origin of V V S can be used.
4. Review oral habits (in BMS).
5. Consider alternations of dentures if needed (in BMS).
6. Relativity large proportions of milder, less chronic cases clear up spontaneously, and even with a minimum intervention, so conservative symptomatic management is of the utmost importance.
Symptomatic therapy consists of:
I. Use of drugs:
1. Some topical agents:
a) Notalgia paraesthetica has been successfully treated with topical application of 0.025% capsaicin cream, EMLA (Eutectic micture of lidocaine and prilocaine) and 5% doxepin (zonolan) cream (a potent H1 and H2 antagonist). Lidocaine and EMLA help to break the peripheral pain circuit, and capsaicin acts on neuropeptides.
b) In VVS application of 5% xylocaine ointment 15 to 30 minutes prior to intercourse and the use of sore protective coating (e.g. petroleum jelly, etc) are useful.
c) In dysesthetic vulvodynia topical 5% lidocaine ointment applied as often as the patients wish is often helpful.
d) In some cases of cyclic vulvoginitis intermittent douching with sodium bicarbonate or vinegar may be beneficial.
e) There are anecdotal reports that topical steroids and capsaicin offer temporary relief.
f) Some patients experience some relief from cold applications to the area.
2. Systemic adminstration of drugs:
a) Trycyclic antidepressants (TCAS),, (amytryptyline, clomipramine, doxepin, imipramine).
Antidepressants are used widely to treat symptoms other than depression, many of which fit into a general category of pain. TCAs are effective in several of these conditions (postherpetic neuralgia, diabetic neuropathy, antypical facial pain, etc). They have serotonergic, noradrenergic, anticholenergic and antihistamine properties. Their analgesic effect differs from their antidepressant effect, in that way that lower dose is sufficient.
They have two roles in managing chronic pain. 1) When the pain relief particularly if the pain is neuropathic, is inadequate, the therapequtic trial of TCAs is justifiable.
2. They can be used in addition to conventional analgesics. Usually at a dose of 50150 mgs/day, they are beneficial in majority of patients. Eeven tetracyclic antidepressants can be tried.
b) Phenytoin and carbamazine are the most commonly used anticonvulsants for the patients who experience paroxysmal stabbing or shooting pains in addition to the constant burning component. The anticonvulsants work by increasing the threshold at which nerve tranmission occurs.
c) There are anecdotal reports that hydroxyzine, some muscle relaxants and intermittent courses of systemic antibiotics offer temporary relief.
d) Consistent longterm anticandidial therapy seems to be successful treatment strategy in cyclic vulvovaginitis.
3. In V V S, there are anecdotal reports of temporary relief of pain from pudendal and epidural nerve block with or without the addition of systemic steriods.
4. Patients with V V S who are recalcitrant to conservative measures sometimes improve with local interferon alpha injections and surgical excision of the painful area with advancement of vaginal mucosa.
5. In V V S at times various forms of laser therapy have been used successfully but therapy carries the risk of worsening the condition.
6. There is some evidence that hormone replacement may help in a few postmenopausal patients.
7. Biofeedback, stress reduction techniques, acupuncture, transepidermal nerve stimulation and muscle relaxation techniques, which have been tried in other pain conditions can be evaluated as alternative therapies.
8. Supportive psychotherapy might be indicated for some patients, in whom chronic pain leads to depression, to help them cope with this problem.
| References|| |
|1.||Bowers KE. Cutaneous and mucosal pain syndromes. Med and Surg Dermatol 1995;2:129-132. |
|2.||Astwazaturow H. Uber parasthetische Neuralgien Und Cine benondere from derselben-Notalgia paraesthetica. Ner-venarzt 1934;133:88-96. |
|3.||Archer CB. The skin and the nervous system. In: RH. Champion, JL. Burton, DA Burns, SM Breathnach, eds, Textbook of Dermatology. 6th Ed. Oxford: Blackwell 1998:2773-2783. |
|4.||Greaves MW. Pruritus. In: RH Champion, JL Burton, DA Burns, SM Breathnach, eds. Textbook of Dermatology. 6th ed. Oxford: Blackwell 1998;617-628. |
|5.||Bernard JD. Neurogenic pruritus and strange skin sensation. In: Bernard JD, ed.Itch: Mechanisms and management pruritus. New York: McGraw-Hill 1994;185-201. |
|6.||Bugalho MJGM, Limbert E, Sobrinho LG, et al. A kindred with multiple endocrine neoplasia type 2a associated with pruritic skin lesions. Cancer 1992;70:2664-2667. |
|7.||Goulden V, Highet A, Shanay H. Notalgia paraesthetica: Report of an association with macular amyloidosis. Clin Exp Dermatol 1994;19:346-349. |
|8.||Massey EW, Pleet AB. Electromyogrophic evaluation of Notalgia paraesthetica. Neurology 1981;31:642. |
|9.||Wallengren J Treatment of notalgio paraesthetica with capsaicin. J Am Acad Dermatol 1991;24:286-288. |
|10.||Leibson I, Honecke H, Mas P Puzzling posterior pigmented pruritic patches. Cutis 1973;23:471-473. |
|11.||Weber PJ, Poullos EG. Notalgia paraesthetica. J AM Acad Dermatol 1988;18:25-30. |
|12.||Springall DR, Kranth SS, Kirkham N, et al. Symptoms of notalgia paraesthetica may be explained by increased dermal innervation. J Invest Dermatol 1991;97:555-561. |
|13.||Sumitra S, Yesudian P Friction amyloidosis: A variant or an etiologic factor in amyloidosis cutis? Int J Dermatol 1993;32:422-423. |
|14.||Walcy KPJ, Elpern DJ. Brachioradial pruritus: a tropical dermopathy. Br J Dermatol 1986;115:177-180. |
|15.||Knight TE, Hayashi T Solar (brachioradial) Pruritus-response to capsaicin cream. Int J Dermatol 1998;33: 206-209. |
|16.||Bech Thomsen N, Thomsen K. Solar pruritus. Acta Derm venereal (stockh) 1995;75:488-489. |
|17.||Bassoe CF. Skin-ache syndrome. J R Soc Med 1995;88:565-569. |
|18.||Cotterill JA. Clinical features of patients with dermatological nondisease. Semin Dermatol 1983;2:203-205. |
|19.||Fienman C, Harris M. Psychogeni facial pain. Br Dent J 1984;156:165-168. |
|20.||Remick RA, Blasberg B. Psychiatric aspects of atypical facial pain. Can Dent Assoc J 1985;12:913-16. |
|21.||Ziskin DE, Moulton R. Glossodynia: a study of idiopathic orolingual pain. J Am Dent Assoc 1946;33:1423-1432. |
|22.||Basker RM, Sturdee DW, Davenport JC. Patients with burning mouths. A clinical investigation of causative factors including the climatric and diabetes. Br Dent J 1978;145:9-16. |
|23.||Rhodus NL, Schwartz BJ, Myers S, et al. Clinical characteristics and substance-p levels of patients with burning mouth syndrome, Oral Surg Oral Med Oral Pathol 2000;89:453. |
|24.||Cotterill AJ. Psychiatry and skin disease. Recent Advances in Dermatology, No.6. Churchill Livingstone; Edindurgh 1983:189-212. |
|25.||Rojo L, Silvestre FJ, Bagan JV, devincente T Psychiatric morbidity in burning mouth syndrome. Psychiatric interview versus depression and anxiety scales. Oral Surg 1993;75:308-311. |
|26.||Browning S, Hislop S, Scully C, et al. The association between burning mouth syndrome and psychological disorders. Oral Surg 1987;64:171-174. |
|27.||Lamb AB, Lamey PJ, Reeve PE. Burning mouth syndrome: psychological aspects. Br Dent J 1988;165:256-260. |
|28.||Bartoshuk MG. Atypical odontalgia: Evidence for damage to the chordo tympani oral Surg oral Med oral Pathol, 2001;91:414. |
|29.||Friedlander AH, Runyon C. Polymyalgia rheumatica and temporal arteritis. Oral Surg oral Med Oral Pathol 1990;69:317-321. |
|30.||Powell FC, Rogers RS. A Practical Approach to oral lesions. Primary care 1983;10:495-511. |
|31.||Bergman M, Ginstrup O, Nilsson B. Potentials of currents between dental metallic restorations. Scand J Dent Res 1982;90:404-408. |
|32.||Van der ploeg HM, van der wal N, Eijkman MAI, et al. Psychological aspects of patients with burning mouth syndrome. Oral Surg Oral Med Oral Pathol 1987;63:664-668. |
|33.||Gruska M. Clinical features of burning mouth syndrome. Oral Surg 1987;83:30-36. |
|34.||Main DMG, Baskar RM. Patients complaining of burning mouth. Br Dent J 1983;154:206-212. |
|35.||Ferguson MM, Carter J, Boyle P et al. Oral complaints related to climacteric symptoms in oropherectomized women. J R Soc Med 1981;74:492-498. |
|36.||Mckay M. Vulvodynia. Dermatol Clin 1992;10:423-433. |
|37.||Edwards L. Gential dermatoses. IN: Holmes KK, sparling PF, Mardh PA, Lemon SM, Stamm WE, plot 0, Wasserheit JN, eds. Sexually Transmitted Diseases, 3th edn. New York: Mc Grow- Hill 1999: 893-902. |
|38.||Mckay M. Vulvodynia, Arch Dermatol 1989; 125:256-262. |
|39.||Ridley CM. International Society for the study of vulvar disease (ISSVD). Report of committee on vulvodynia. J reprod Med 1993;38:14. |
|40.||IVE FA. The umbilical, perianal and genital Regions, In: RH Champion, JL Burton, DA Burns, SM Breathnach, eds. Textbook of Dermatology, 6th ed. Oxford: Blackwell 1998;3163-3238. |
|41.||Mckay M. Vulvodynia: A multifactorial problem. Arch Dermatol 1989;125:256. |
|42.||Holmes KK, Stamm WE. Lower Gential tract infection syndromes. In: Holmes KK, sparling PF, Mardh PA, Lemon SM, Stamm WE, Piot P, Wasserheit JN, eds. Sexually transmitted diseases, 3rd edn. New York: McGraw-Hill 1999;761-781. |
|43.||Mckay M. Subsets of vulvodynio. J Reprod Med 1988;33:695. |
|44.||Marinoff SC, Turner MLC. Vulvar vestibulitis syndrome. Dermatol Clin,1992;10:435-444. |
|45.||Friedrich EG Jr. Vulvar vestibulitis syndrome. J Reprod Med 1987;32:110-114. |
|46.||Turner MLC. Gential disorders In: KA Arndt, PE Leboit, JK Robinson, BU Wintroub, eds. Cutaneous Medicine and Surgery. Philadepphia: WB sounders 1996:1340-1359. |
|47.||Furlonge CB, Thin RN, Evans BE, et al. Vulvar vestibulitis syndrome. A clinico-pathological study. Br J Obstet Gynecol 1991;98:706-709. |
|48.||Goetsch ME. Vulvar vestibulitis: prevalence and historic features in general gunecologic practice population. Am J Obstet Gynecol 1991;164:1609-1616. |
|49.||Solomons CC, Melmed MH, Heitler SM. Calcium citrate for vulvar vestibulitis. A case report: J Reprod Med 1991;36:879-882. |
|50.||Layzer RB, Connant MA. Neuralgia in recurrent herpes simplex. Arch Neural 1974;31:233-237. |
|51.||Howard EJ. Postherpetic pudendal neuralgia. JAMA 1985;253:2196. |
|52.||Amarenco G, Lecocquen-Amarenco A, Kerdraon J, et al. Perineal neuralgia. Presse Med 1991;20:71-74. |
|53.||Turner MLC, Morinaff SC. Pudendal neuralgia. Am J obstet Gynecol 1991;165:1233-1236. |
|54.||Lynch PJ, et al. Anogential Pain In: Gential Dermatology. New York: Sounders 1994:247-248. |
|55.||Neil ME, Swash M. Chronic perianal pain: an unresolved problem. JR Soc Med 1982;75:96-101. |
|56.||Parks AG, Porter NH, Hard Castle J. The Syndrome of descending perineum. Proc R Soc Med 1966;59:477-482. |
|57.||Lask B. Chronic Perinnal pain. JR Soc Med 1982;75:370. |
|58.||Kelly CA. Antidepressants and chronic pain (Editorial). BMJ 1997;314:336-337. |
|59.||Swerdlow H. Review; Anticonvulsant drugs and chronic pain. Clin Neuropharmacol 1984;7:51-82. |
|60.||Bensigor-Le HenaffM, LabatJJ, RobertR, etal. Perineal Neuralgia in connection with suffering pudendal nerves. Agressologie 1991;5:277-279. |
|61.||Wardrop RW, Hailes J, Burger M, et al. Oral discomfprt at menopause. Oral Surg 1989;67:535-548. |