Congenital Insensitivity To Pain Research Articles

Tension-type headache as the unique pain experience of a patient with congenital insensitivity to pain

Congenital insensitivity to pain (CIP) is a rare clinical syndrome characterized by dramatic impairment of pain perception since birth and is generally caused by a hereditary sensory and autonomic neuropathy (HSAN) with loss of the small-calibre, nociceptive nerve fibres. We report the case of a 32-year-old woman with CIP and a presumptive diagnosis of HSAN type V, who experienced physical pain for the first and unique time in her life shortly after the sudden loss of her brother. This patient had sustained innumerable painless injuries during childhood, including bone fractures and severe burns. The only pain she ever felt consisted in an intense headache, which took place in a context of strong emotional overload and anxiety, 3 weeks after her younger brother died suddenly in a car accident. The description of this inaugural episode of headache fulfilled the diagnostic criteria of episodic tension-type headache. This case strongly suggests that the transcription of the grief of bereavement into physical pain may sometimes occur independently of the peripheral mechanisms of nociception and despite the lack of previous pain experience. In the light of recent experimental data showing that the same neural mechanisms that regulate physical pain may also control the expression of separation distress and the feeling of social exclusion, this unique case helps to better understand why some patients may feel physically hurt after the loss of someone they love.

Anesthetic Management of a Child With Congenital Insensitivity to Pain With Anhydrosis

1. Notami K, Satoh C, Hashimoto J, et al: Intracranial Aspergillus infection from the paranasal sinus. Oral Surg Oral Med Oral Pathol 89:9, 2000 2. Meyer RD: Aspergillus species, in Gordobach SL, Bartlett JG, Blacklow NR (eds): Infectious Diseases. (ed 2). Philadelphia, PA, Saunders, 1998, pp 2327-2334 3. Napoli JA, Donegan JO: Aspergillosis and necrosis of the maxilla: A case report. J Oral Maxillofac Surg 89:532, 1991 4. Kim DG, Hong SC, Kim HJ et al: Cerebral aspergillosis in immunologically competent patients. Surg Neurol 40:26, 1993 5. Myoken Y, Sugata T, Kyo T, et al: Pathologic features of invasive oral aspergillosis in patients with hematologic malignancies. J. Oral Maxillofac Surg 54:263, 1996 6. Ellis M, Richardson M, de Pauw B: Epidemiology. Hosp Med 61:605, 2000 7. Waxman JE, Specter JC, Sale SR, et al: Allergic Aspergillus sinusitis. Concepts in diagnosis and treatment of a new clinical entity. Laryngoscope 97:261, 1987 8. Talbot GH, Huang A, Plovench M: Invasive Aspergillus rhinosinusitis in patients with acute leukemia. Rev Infect Dis 13:219, 1991 9. Beal WF, O’Carrol CP, Kleinman GM, et al: Aspergillosis of the nervous system. Neurology 32:473, 1982 10. Meikle D, Yarington CT, Winterbauer RV: Aspergillosis of the maxillary sinuses in otherwise healthy patients. Laryngoscope 95:776, 1985 11. Henderson VJ, Hirvela ER: Emerging and reemerging microbial threats. Nosocomial fungus infections. Arch Surg 131:330, 1996 12. Walsh TJ, Hier DB, Caplan LR: Fungal infections of the central nervous system: Comparative analysis of the risk factors and clinical signs in 57 patients. Neurology 35:1654, 1985 13. Walsh TJ, Pizzzo PA: Nosocomial fungal infections: A classification for hospital-acquired fungal infections and mycoses from endogenous flora or reactivation. Annu Rev Microbiol 42:517, 1998 14. Saah D, Drakos PE, Elidan J, et al: Rhinocerebral aspergillosis in patients undergoing bone marrow transplantation. Annu Otol Rhinol Laryngol 103:306, 1994 15. Mauriell JA, Yepez N, Mostatavi R, et al: Invasive rhinosinoorbital aspergillosis with precipitus visual loss. Can J Ophthalmol 30:124, 1995

Knee dislocation in a patient with congenital pain insensitivity?a case report

This case report describes a patient who suffered a knee dislocation with a vascular injury following a high-velocity injury. In addition he suffered with congenital pain insensitivity. As a result there was a delay in diagnosing his major injury. In addition he underwent conservative therapy despite multidirectional knee instability. After a prolonged course of non-operative treatment, he underwent reconstruction of anterior and posterior cruciate ligaments. Following operative treatment, knee stability was dramatically improved. The case report highlights the difficulties in diagnosing patients with major injuries who suffer with pain insensitivity and shows that operative treatment for the multidirectional knee instability gives a more favourable outcome than non-operative treatment.

The changing sensitivity in the life of the nociceptor

Plasticity of the central nervous system has been shown to be an important correlate in the generation of chronic pain. However, there is now also increasing evidence for profound changes of the primary sensory neurons including nociceptors throughout the life of an organism and these changes account for clinically relevant alterations of pain perception. During development sensory neurons require one or more growth factors that rescue neurons during critical periods of programmed cell death and growth factors also play an important role for the development of the appropriate phenotype. Neurotrophin-3 may initially have an effect on proliferation of many subtypes of sensory neurons including cells destined to become nociceptors during early development. During a critical period of late prenatal development nerve growth factor (NGF) signalling through its cognate high affinity receptor trkA has been shown to be the main survival factor during a critical period of prenatal development. Humans deficient of trkA suffer from the rare disorder of congenital analgesia. Postnatally, the subpopulation of non-peptidergic nociceptors lose their ability to respond to NGF, start to express receptor element for and begin to respond to glial cell line-derived neurotrophic factor (GDNF). Both NGF and GDNF have also been shown to regulate the sensitivity of nociceptors to heat and capsaicin in the adult. Changes in the levels of endogenous trophic factors have also been implicated for the generation of ongoing activity and sensitisation to heat that are the hallmark of nociceptors innervating inflamed tissue. Whereas the development of ongoing activity correlates with the intensity of ongoing pain, sensitisation of nociceptors to heat can explain the hyperalgesia to heat that typically accompanies inflammatory lesions in the skin. Dramatic changes of nociceptor phenotype occur following nerve injury. Sensory neurons, including nociceptors, start to express adrenoceptors and become responsive for catecholamines and these changes appear to be responsible for the development of sympathetically maintained pain in some patients.

Somatic pain–pathogenesis and prevention

because it is a key component of the body’s normal defence mech- anisms, protecting the body from a potentially hostile external environment by initiating behavioural and reflex avoidance strategies. This protective mech- anism operates as a result of the presence of a specific set of primary sensory neurones which encode the intensity, duration and quality of any noxious stimulus and, by virtue of their topographically organized projections to the spinal cord, its location [108]. Absence of these nociceptors, as in patients with congenital analgesia or peripheral neuropathies, is associated with tissue damage and poor healing as a consequence of the absence of the normal protective reflexes and behavioural responses elicited by the nociceptors. This “ouch” pain is, therefore, an important and adaptive element of the normal nervous system which, clinically, only needs to be temporarily suppressed or disabled during surgical procedures where damage is deliberately produced. The nociceptors terminate in a highly ordered way in the dorsal horn of the spinal cord with the thinly myelinated A ending in laminae I and V and the unmyelinated C-fibres in lamina II. These high threshold sensory fibres activate a large number of second order interneurones and projection neurones in the spinal cord, some of which are activated exclusively by noxious stimuli (

Plasma beta-endorphin levels and natural-killer cells in two cases of congenital indifference to pain.

We have investigated plasma beta-endorphin (beta-E), ACTH, and cortisol in two cases of congenital indifference to pain (CIP), a rare syndrome characterized by unresponsiveness to painful stimuli. As the two patients had frequent skin infections, we also studied lymphocyte response to mitogens in the absence or presence of beta-E. In addition, we explored a series of lymphocyte membrane antigens related to different aspects of the immune response, such as CD3+, CD4+, CD8+, B, NK Leu 7, Leu 9, and Leu 19, anti-interleukin-2 receptor (anti-TAC). Plasma beta-E levels in the two patients were significantly higher than in controls, whereas plasma ACTH and cortisol levels were normal. Lymphocyte response to the mitogen phytohemagglutinin was normal. The expression of Leu 7, Leu 9, and Leu 19, three antigens related to natural killer cells, was decreased by about 50%. The results indicate that in the two cases of CIP studied, high plasma beta-E levels are associated with a reduction in the expression of natural killer cells. This suggests that the two phenomena are specifically related to each other. These data represent further evidence of the possible pathophysiological relevance of the neuroendocrine-immune feedback.

Anaesthesia for congenital analgesia

Bilateral amputations were performed without analgesia on a patient with congenital insensitivity to pain (congenital analgesia). Positioning, vasomotor control and possible sensitivity to anaesthetic drugs are discussed.

Congenital absence of pain

Congenital absence of pain

Chronic pain: Principles of management

PAIN is an essential part of human sensory experience. It warns of external threat and internal illness and it provides the physician with a major diagnostic tool. Congenital absence of pain is a disabling, even deadly, disease? Yet pain as suffering is visited upon millions; it is a common, pressing reason for seeking medical help. Acute pain usually responds readily to appropriate treatment; both patients and physicians cope with it quite well. Chronic pain, with its many psychological and physical manifestations, is a far more difficult, frustrating problem. However, recent advances in the understanding of pain mechanisms, improved means of delivering older therapies, and development of new modalities of treatment have brought some hope to this previously gloomy field. Pain as suffering differs from pain as a specific sensation. The former is a psychological experience associated with, or at least described in terms of, tissue damage. The latter, designated nociception, is the neurophysiologic means of detection of tissue damage. Although usually closely related, suffering and nociception can exist independently, as in the opposing cases of pain-free celebrants of tissue-damaging religious rituals and patients with psychogenic pain. Understanding the current treatment of pain requires some knowledge of its neuroanatomy, neurochemistry, and psychology.

Congenital analgesia: Report of a case

Extensive injury to the tongue of a child led to the diagnosis of congenital analgesia. The injury was the first symptom of this dysfunction.

Isolation of a new urine metabolite excreted in generalized congenital analgesia

A new urinary metabolite was identified in eight cases of congenital analgesia, and was shown to be absent in numerous other normal and abnormal patients. The metabolite is excreted in a conjugated form, being hydrolyzed by acid. The isolation and purification of this metabolite is described. Color reactions, infrared and ultraviolet spectra suggest an aromatic amine, with a molecular weight around 214–233. The relation of this metabolite to the pain mechanism is discussed.

In Vitro Uptake of Labelled Amino Acids by the Skin of Children with Generalized Congenital Analgesia

SummaryThe “in vitro” uptake of labelled tyrosine, tryptophan and leucine by the skin of two children with GCA (Generalized Congenital Analgesia) was compared with that in normal (white and negro) individuals. Through radioactivity counts and radioautographic procedures it was shown that the uptake of the two aromatic amino acids was reduced in the GCA individuals the protein synthesis seemed to be normal.The possible relationship of these results to an abnormal metabolite isolated from the urine of these patients is discussed.

Nerves in the Skin of a Patient with Familial Dysautonomia (Riley-Day Syndrome)

The nerves in the skin of a patient with Riley-Day syndrome were studied by silver and cholinesterase techniques. Sensory nerve end-organs, nerve fibers, and autonomic nerve plexuses were found in normal distribution. Cholinesterase was observed in the sensory end-organs and the autonomic plexuses. It is proposed that the absence of axon flare in these patients, unlike patients with congenital analgesia, must rest on some pharmacologic abnormality, since the anatomy and histochemistry of the cutaneous nerves are normal.

Physiopathogenesis of pain

O estudo da dor é um capítulo do estudo das bases neurofisiológicas da sensação, pois a dor nada mais é que uma sensação de conteúdo desagradável originada por estímulos nocivos. Enquanto a função das outras modalidades sensoriais é informativa ou gnósica, a dor é de proteção. O estudo da fisiología da dor compreende o estudo dos receptores, dos estímulos, das vias, das estruturas do sistema nervoso central que partici- pam da fisiología da dor, da percepção dolorosa e das reações motoras e neurovegetativas. São analisados os receptores e as vias e discutidas sua especificidade, assim como a transmissão da dor rápida e lenta por vias nervosas diferentes até o córtex cerebral. É comentada a influência da atenção na intensidade da percepção dolorosa e, com base em estudos experimentais, é considerado que o circuito retículo-córtico-reticular seja indispensável para a percepção da dor. No tocante à patologia da dor é examinada a insensibilidade congênita à dor, sendo admitida a hipótese de que em algumas sinapses é modificado o esquema de impulsos que darão lugar à sensação dolorosa. É destacado o papel do lobo frontal como parte de um mecanismo pòtenciador que condiciona o sofrimento geral do paciente. A dor referida é explicada pela teoria da "convergência-projeção" de fibras viscerais com fibras cutâneas dolorosas sôbre o mesmo neurônio em algun ponto da via sensitiva. O resultado da hipofisectomia trazendo uma diminuição ou anulação da dor no câncer do seio abre debates em tôrno do papel dos hormônios na percepção dolorosa.

Isolation of a new urine metabolite excreted in generalized congenital analgesia

Abstract A new urinary metabolite was identified in eight cases of congenital analgesia, and was shown to be absent in numerous other normal and abnormal patients. The metabolite is excreted in a conjugated form, being hydrolyzed by acid. The isolation and purification of this metabolite is described. Color reactions, infrared and ultraviolet spectra suggest an aromatic amine, with a molecular weight around 214–233. The relation of this metabolite to the pain mechanism is discussed.

The electrodermogram (Tarchanoff effect) during sleep

The electrodermal response (Tarchanoff effect) was studied during sleep. 1. 1. Spontaneous EDRs were usually rare during wakefulness but, even if frequent, did not undergo striking changes during falling asleep. They increased in number with passage to stage IV. During stage II they were isolated or related to K complexes and, occasionally to the presence of generalized myoclonic jerks. During stage III and IV they frequently became virtually continuous. In stage I rem, however, they were infrequent and were either isolated or associated with bursts of rapid eye movements (REMs) and any of: partial myoclonic jerks, tachycardia or respiratory changes. 2. 2. EDRs could be elicited by various stimuli in all stages, always with a 1–4 sec latency. In stage II, III and IV the threshold was lowered, whereas in stage I rem it was quite high. In stage II, successful stimuli provoked a K complex before the EDR and rarely, a startle response. In stages III and IV the EEG changes were usually less marked whereas other autonomic reactivity persisted. EDRs provoked in stage I rem were sometimes associated with EEG changes (e.g., blocking of “saw-toothed” waves or a burst of posterior alpha activity) but not with partial jerks or REMs. 3. 3. Topographically, the EDR in all phases was seen to diffuse from the head caudally down the body axis and peripherally along the limbs, where conduction occurred at approximately 1 m/sec. In stage I rem apparently randomly distributed EDRs were occasionally recorded. 4. 4. In further studies EDRs were noted with various episodic sleep phenomena (enuresis nocturna, somnambulism, etc), certain abnormal movements, focal epileptic temporal lobe discharges, generalized or hemigeneralized epileptic discharges, and tonic epileptic seizures, even when reduced to their minimal expression. 5. 5. Prefrontal bilateral lobotomy, hemispherectomy, or congenital agenesis of the corpus callosum did not influence the evolution of the EDG. Congenital analgesia was associated with difficulty in provoking EDRs by painful stimuli. 6. 6. The apparent neurophysiological basis and certain psychological correlations are discussed.

Neuropathic Fracture

NEUROPATHIC bone and joint disease has been described in diabetes mellitus complicated by neuropathy, as well as in neurosyphilis, syringomyelia, congenital absence of pain, leprosy, congenital and acquired spinal cord lesions, and following peripheral nerve damage and intra-articular hydrocortisone injections.¹In diabetes, the changes usually seen are those of painless destruction of the tarsal joints, and occasionally of the ankles and knees. When found, they are usually present in association with other neurological features that have received the name of pseudotabes: Argyll-Robertson pupils, postural hypotension, nocturnal diarrhea, gastric atony, bladder dysfunction, pilomotor and sudomotor deficiencies, impotence, and edema. In addition, retinopathy and nephropathy are commonly present, completing the "triopathy" associated with long-standing diabetes mellitus. The present case report deals with a fracture of the tibia and fibula in a diabetic patient possessing many manifestations of pseudotabes and "triopathy." The history and nature of the fracture indicate that it was of

Congenital Absence of Pain

Congenital Absence of Pain

Congenital Absence of Pain

Congenital Absence of Pain

Congenital absence of pain. Report of a case and experimental studies.

Although a life without pain sounds Utopian, it is possible. Individual human organisms can develop and function—some of them in a fairly normal manner—without the information, the protective reflexes, or the paradoxical pleasure that pain affords. Some persons can tolerate specific stimuli that would be excruciating to the physiologically normal, and there are rare individuals who have a more or less generalized analgesia. Review and Description Reports and reviews of 45 such cases have been published, from Dearborn's 1 single instance in 1932 to the well-studied patients and stimulating discussion of Ogden, Robert, and Carmichael 2 in 1959. Fanconi and Ferrazzini 3 had summarized the literature in 1957. Kipnis and associates 4 in 1954 had noted that the studies performed had been adequate in only 11 cases and had mentioned that these were a heterogeneous group, for 6 of the patients had perceived pain occasionally and 2 of them had