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Effects of dizocilpine on autotomy behavior after nerve section in mice.

The effects of acute administration of dizocilpine (MK-801) at different perioperative times on autotomy behavior after sciatic and saphenous nerve transection were studied in the mouse. Control mice developed a severe self-mutilating behavior starting 1-3 days postoperation and reaching a maximum by 11 days. Mice injected with a single dose of dizocilpine (0.4 mg/kg i.p.) before operation, the 1st or 3rd postoperative day autotomized significantly less than controls. An 1-wk treatment with the same dose once a day did not show further benefit. A single administration of dizocilpine the 5th day after surgery slightly halted further progression of autotomy. Dizocilpine did not have any deleterious effect on normal peripheral nerve function. These results suggest that NMDA receptor blockade prevents development of hyperalgesia and neuropathic pain after peripheral nerve injuries but only when it is administered before or during the first 3 days after injury.

Animals↗

Galanin antisense oligonucleotides reduce galanin levels in dorsal root ganglia and induce autotomy in rats after axotomy.

Antisense (AS) oligonucleotides (ONs) to galanin (GAL) were applied to the proximal end of a transected sciatic nerve, allowing their cellular uptake and transport into injured axons. GAL expression in dorsal root ganglia and self-mutilation behavior (autotomy) were then studied. AS-ONs with phosphorothioate or allyl modifications significantly suppressed the axotomy-induced increase in GAL levels, as demonstrated by immunohistochemistry and exaggerated autotomy behavior, whereas no significant effect on GAL mRNA levels could be demonstrated with in situ hybridization. Allyl-ONs were more effective than phosphorothioate-ONs. An AS-ON with three base mismatches did not induce any of the above effects. These results support the view that the inhibition of axotomy-induced GAL up-regulation is related to autotomy.

Animals↗

Behavioral and electrophysiological effects of various types of peripheral nerve lesions in the rat: a comparison of possible models for chronic pain.

Three types of nerve lesions involving the brachial plexus were produced in rats: (1) multiple dorsal rhizotomy; (2) spinal nerve section just distal to the dorsal root ganglia (DRG); (3) section of the median, ulnar and radial nerves. The 3 types of lesion caused self-mutilation (autotomy) of the denervated forelimb. Significant differences were found in the time course and severity of this abnormal behavior among the 3 groups. Rats that had undergone spinal nerve lesion (group 2) performed significantly less severe autotomy than rats with dorsal rhizotomy (group 1) or peripheral nerve lesions (group 3). The latency to the onset of autotomy was significantly shorter for group 2 than for groups 1 and 3. Electrophysiological investigation of rats in group 2 revealed neural activity in the dorsal roots. The characteristics of the neural discharge were largely a function of postoperative survival times. The possible role of the various types of nerve lesion in producing chronic pain states is discussed.

Afferent Pathways↗

Primary sciatic nerve repair using titanium staples.

The primary epineural repair of human peripheral nerves is most often achieved using non-absorbable microsutures, which can elicit a foreign-body reaction. We describe a new system for neural-tissue approximation, consisting of non-penetrating vascular closure staples (VCS) applied to the epineurium. These clips were initially developed for use in microvascular anastomosis, with no knowledge of their effectiveness in neural-tissue approximation. We compare the efficacies of VCS clips and monofilament nylon microsutures in the repair of transected sciatic nerves in 36 adult Sprague Dawley rats (18 treated with 9/0 sutures and 18 treated with VCS clips). In the rat, regeneration starts by day 5, and is well advanced by 4 weeks. To assess the overall repair success, the site of injury, after perfusion fixation, was harvested at 5, 7 and 30 days. The two methods were compared in terms of operative time, the degree of self-mutilation (autotomy), the macroscopic specimens in vivo and the microanatomical continuity through the repair site. Continuity was studied by using PGP-9.5-labelled cryosections and fluorescent secondary antibodies to visualise axonal regeneration. Clip repair was significantly faster in the VCS group (mean +/- s.e.m. = 7.09 +/- 0.36 min versus mean +/- s.e.m. 11.56 +/- 0.51 min in the sutured group) and an equal and minimal degree of autotomy was observed. Macroscopically, all 36 nerves were in continuity and free from neuroma. The use of VCS clips resulted in equivalent visualised regeneration across the repair site at each time point. We believe the use of VCS clips to be a faster and comparable alternative to non-absorbable sutures in primary nerve repair in this experimental model.

Animals↗

Neurologic crises in hereditary tyrosinemia.

Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.

Acute Disease↗

Up-regulation of cholecystokinin in primary sensory neurons is associated with morphine insensitivity in experimental neuropathic pain in the rat.

We examined the distribution of mRNA for the peptide cholecystokinin (CCK) with in situ hybridization in adult rat lumbar dorsal root ganglia following unilateral section of the sciatic nerve, as well as the effect of systemic CI 988, a selective antagonist of the CCK type B receptor, applied alone or in combination with intrathecal (i.t.) morphine, on the self-mutilating behavior of rats (autotomy) after axotomy, a sign of neuropathic pain and/or dysesthesia. There was a dramatic increase in the number of neurons in dorsal root ganglia synthesizing the peptide cholecystokinin (CCK) after sciatic nerve section. Furthermore, the autotomy behavior of rats was significantly inhibited by chronic i.t. administration of morphine in conjunction with subcutaneous (s.c.) injection of CI 988. Neither i.t. morphine nor s.c. CI 988 alone produced a comparable effect on autotomy. Our results suggested that up-regulation of the mRNA for CCK in primary afferents after nerve injury may be related to the clinical phenomenon of opioid insensitivity. Thus, coadministration of CCK antagonists in combination with opioids may offer a new approach in treating neuropathic pain.

Animals↗

[The "Moi-peau"].

To construct a coherent identity, humans must distinguish what belongs to the external, perceived world from what belongs to their own inner world and the inner world of other individuals. Based on the theory developed by S. Freud and on work by ethologists, a number of psychoanalysts (J. Bowlby, R.A. Spitz, D.W. Winnicott, etc.) have underlined the importance of early tactile exchanges with the mother if a child is to become an autonomous individual who feels secure within what he or she perceives to be sound and reliable mental and physical boundaries. More recently, other psychoanalysts (E. Bick, W.R. Bion, etc.) have studied the fantasized mental structures that form the limits between an individual's inner mental space and the external world (including other individuals). As part of this theoretical psychoanalytical movement, Didier Anzieu, a French psychoanalyst, started to develop the concept of the "Moi-peau" in 1974. The "Moi-peau" designates a fantasized reality that a child uses during its early development to represent itself as "me", based on its experience of the body surface. The child, enveloped in its mother's care, fantasizes of a skin shared with its mother: on one side the mother (the outer layer of the "Moi-peau"), and on the other side the child (the inner layer of the "Moi-peau"). These two layers must separate gradually if the child is to acquire its own me-skin. D. Anzieu's work allowed dermatologists and other specialists, such as pediatricians, to focus on the quality of early tactile exchanges between a mother and her child, including the child with a chronic skin disorder. It also helped dermatologists to recognize patients with "borderline" states, which are particularly frequent in dermatology (ereutophobia, dysmorphophobia, tattooing, self-mutilation, artefacta dermatitis). These borderline patients are adults who, as a result of their mental conflicts, adopt defense mechanisms derived from both neurotic and psychotic functioning. Their complaints reflect difficulties with the solidity of their mental and physical limits: their real skin is metaphorically linked to the fantasized mental structure that delimits the individual mental space. Among other clinical characteristics, they have a "pathology of action" and frequently attack their own skin, paradoxically, in order to test the solidity and reliability of their own limits. Finally, D. Anzieu's work encouraged dermatologists to use psychotherapeutic approaches in parallel to classical dermatologic approaches, when necessary, and helped them better understand how psychoanalysts work with patients who have not yet acquired their own "Moi-peau". As a result, D. Anzieu was among the first to reconcile dermatologists and psychoanalysts.

Adult↗

What is reflex sympathetic dystrophy?

In the literature there is no unanimity with respect to the diagnosis of reflex sympathetic dystrophy (RSD). Frequently, the diagnosis is established on mere clinical grounds. In our opinion, however, bone scintigraphy is of major importance for the diagnosis. Using this examination, true RSD can be clearly differentiated from other conditions which are incorrectly diagnosed and treated as RSD. If the bone scan is not suggestive of RSD, the clinical picture, radiological examination and vascular scan may lead to the correct diagnosis. This may be a pseudodystrophy, in which a hypovascularization is found right from the start, while in true RSD there is initially a hypervascularization. Other conditions which may be confused with RSD are causalgia, neurotic compulsive postures, hysterical conversion, malingering and even self-mutilation. In the spontaneous course of RSD three phases can be distinguished. Stage I is the warm or hypertrophic phase, stage II the cold or atrophic phase. Per definition the third phase corresponds to stabilization or, in rare instances, to healing. By means of the vascular scan the correct stage can be determined, and the results of treatment evaluated. Finally it should be noted that in children the condition is completely different from true RSD, as it concerns a pseudodystrophy or disuse-related dystrophy. This condition may also be seen in adults and adolescents, usually females. The bone scan is always negative. In this way bone scintigraphy constitutes the means to answer the question as to what RSD is and what it is not. An algorithm for the differential diagnosis is presented.

Adolescent↗

Strain differences in autotomy in rats undergoing sciatic nerve transection or repair.

The degree of self-mutilation (autotomy) following sciatic nerve injury was assessed in 6 rat strains. Experimental groups included sciatic nerve transection with and without repair and crush lesions. The degree of autotomy was measured using a standard grading system. There were statistically significant differences between the strains in the transected group in terms of both degree of autotomy and the time of onset of its appearance. The repair group showed a shorter mean time of onset, lower maximal scores, and lower percentage of affected animals. Autotomy was absent in the nerve crush group and in all Lewis rats. In experimental studies when the status of the foot is critical (e.g., to evaluate functional walking patterns) Lewis rats appear to be the most appropriate strain to utilize. These results suggest that there are definite strain differences in the degree of autotomy following nerve transection or repair.

Animals↗

Penile resurfacing with vascularized fascia lata.

Penis resurfacing is a challenging procedure, and should simultaneously ensure erectile function, tactile sensibility, sexual satisfaction, and aesthetic integrity. This article presents three cases with penile skin defects treated by means of a pedicled fascia lata attached either to the tensor fascia lata (one case) or an anterolateral thigh flap (two cases). The cause of the wounds included electrical burn, Fournier's gangrene, and self-mutilation. The size of flaps ranged from 10-13 cm in width and 15-30 cm in length. All flaps included vascularized fascia lata, which covered part or the circumference of the penis. All flaps survived completely. The lateral cutaneous nerve of the thigh was included in the designed flaps in all instances, and normal protective sensation was recorded postoperatively. The patients reported normal erectile function and ability to perform intercourse. The flaps, though relatively bulky and hairy, had a good color and texture match with the penis and suprapubic region. Based on our limited experience, we believe that the anterolateral thigh flap has greater dimensions with a longer pedicle, and allows for greater flexibility in flap design compared to the tensor fascia lata flap. An anterolateral thigh flap can be safely thinned in a second stage, and it is our flap of choice for penis resurfacing.

Adult↗

Procedures which increase acute pain sensitivity also increase autotomy.

Rats typically display self-mutilation (autotomy) of a paw that has been denervated by transection of the sciatic and saphenous nerves. The cause of autotomy, however, is not known. It may be due to hyperesthesia (comparable to that seen in humans after peripheral nerve injury) or anesthesia (as an attempt to shed an insensate appendage). The present study tested the assumption that if autotomy is produced by pain, then procedures that normally augment the expression of pain should enhance autotomy after transection of peripheral nerves. Groups of rats were subjected to procedures known to produce an increase in pain sensitivity: (i) prior heat injury of either the ipsilateral or contralateral paw; (ii) systemic injection of noradrenaline and the monoamine oxidase inhibitor, pargyline; and (iii) intrathecal administration of substance P. The results showed that each of these procedures produced an increase in the level of autotomy. These results strongly suggest that autotomy is due to a sensory phenomenon which, in terms of human experience, would be described as pain or dysesthesia.

Animals↗

Congenital sensory neuropathy with anhydrosis-a case report and investigation of autonomic nervous system abnormalities.

A review of the clinical profile of congenital sensory neuropathy with anhydrosis is presented. It is stressed that major diagnostic criteria of this recessively inherited condition should be limited to insensitivity to pain with normal tactile perception, anhydrosis, recurrent unexplained fever, self-mutilation, mental retardation, hypotonia, histologically normal sweat glands and variable autonomic abnormality. A case conforming to this description is reported and compared with 13 published cases. Special investigations of the autonomic nervous system through measurement of urinary catecholamine metabolites and psychophysiologic variables were conducted on this patient. Based on the analysis of 5 X 24-hour urine, values of metabolites of dopamine and epinephrine were normal. Metabolites of norepinephrine, such as 3-methoxy-4-hydroxy phenylglycol and normetanephrine, however, were significantly low when compared with those of four controls, suggesting decreased peripheral and central norepinephrine activity. Polygraph recording and evaluation of some orienting response components revealed no obvious signs of autonomic perturbation and, specifically, no phasic electrodermal activity. These two findings (biochemical and electrodermal) strongly suggest an autonomic imbalance, specifically component, both central and peripheral. It is suggested that autonomic disorder is an integral part of the syndrome and may be demonstrated by special investigations.

Autonomic Nervous System Diseases↗

[Autocastration of a young schizophrenic man].

OBJECTIVE: Self-mutilation of the genitals in man is a rare phenomenon mainly occurring in young males. The importance of conflicts about the male role, difficulties with the male identification in childhood and feeling of guilt for sexual offences are discussed in the literature. The influence of developmental crisis on this symbolic form of automutilation will be discussed in our case report. METHOD: We present a case of a young schizophrenic man whose illness started in adolescence. He committed genital automutilation already in early adolescence, as a young male he autocastrated himself. DISCUSSION: We demonstrate the connection of specific problems of development in adolescence and psychopathology. Autocastration will be discussed as a "psychotic" solution of the adolescent conflict of dependence. CONCLUSIONS: Developmental conflicts may be important pathoplastic factors who may lead to severe psychopathology and misbehavior. Additionally to a psychopharmacological treatment a specific adolescent- and conflictoriented psychotherapy for solving the developmental conflicts in young schizophrenic patients should be established.

Adolescent↗

Neonatal guanethidine sympathectomy suppresses autotomy and prevents changes in spinal and supraspinal monoamine levels induced by peripheral deafferentation in rats.

In the rat, sciatic and saphenous nerve section resulted in self-mutilation of the ipsilateral limb. Fifteen and 60 days after surgery, monoamine levels were altered not only in the spinal cord but also in supraspinal structures. Thus, in the ipsi- and contralateral sides of the spinal lumbar region, an increase in the levels of 5-hydroxyindoleacetic acid (5-HIAA) was observed 15 days after surgery and in the levels of serotonin (5-HT) and noradrenaline 60 days later. Changes in the content of 5-HT and its metabolite were also evident, at these time points, in periaqueductal gray matter and trigeminal nucleus. Chemical sympathectomy carried out by administering guanethidine to neonatal rats reduced the degree of autotomy and suppressed the changes in monoaminergic systems following peripheral neurectomy. This study supports the hypothesis that the local noradrenaline outflow from sympathetic fibers in the neuroma is one of the causal factors in autotomy and it indicates that autotomy is under the control of descending monoaminergic pathways originating in brain-stem nuclei.

Animals↗

Neuroma pain model: correlation of motor behavior and body weight with autotomy in rats.

A rat pain model was investigated by examining the correlation of autotomy (self-mutilation) score with motor behavior and body weight change after sciatic nerve transection, encapsulation and neuroma formation. Observations of motor behavior and body weight changes (e.g. feeding behavior) as an index of pain were considered to have several advantages over scoring the degree of autotomy. Motor activity of 14 rats (12 neuroma, 2 sham), measured using a stabilimeter, was compared on a weekly basis to autotomy scores for a total of 7 weeks after surgery. Additionally, body weight of 26 rats (20 neuroma, 6 sham surgery) was monitored for 4 weeks following surgery. While autotomy, changes in body weight and abnormalities in motor behavior were observed after surgery, no significant Spearman rank correlation coefficients were determined for any week and thus no significant relationships were found between autotomy score and motor activity or body weight. However, it was observed that rats after sham surgery gained significantly more weight than rats after sciatic nerve transection. Therefore, these results cast doubt on the validity of autotomy score as the sole index of pain.

Animals↗

[Enucleation as a form of self-aggression--2 case reports and review of the literature].

BACKGROUND: Autoenucleation is the worst form of self-mutilation of the eye. Patients affected are mostly those with psychosis and delusions, but such acts can also happen under the influence of drugs, alcohol, solvents and seldom with organic illnesses. Often, these patients are known to be autoaggressive and suicidal. PATIENTS: We present two psychiatric patients who autoenucleated one eye and injured the other. A 41-year-old patient with known organic epilepsy based on a temporal-lobe-hemangioma and psychosis with delusions autoenucleated his right eye and lacerated the conjunctiva of the other, following imperative voices. A 50-year-old female suffered from a long-standing paranoid schizophrenia and religious delusions, and autoaggressive acts with resulting amaurosis of the right eye and several suicidal attempts had preceded the autoenucleation of the left eye. DISCUSSION: After the completion of the autoaggressive act the patients experience relief, but often the autoaggresive or suicidal impulses persist or recur. A close cooperation between ophthalmologists and psychiatrist in these patients is imperative.

Adult↗

Self-destructive dermatoses.

It appears certain that the causes of self-destructive dermatoses are many and complex. The disorder spans diagnostic categories and varies from unconscious picking at the skin to severe self-destructive actions. Although not limited to any one diagnosis, skin disorders appear to be more prevalent in depression. This association may involve activation of the hypothalamic-pituitary-adrenal axis commonly found in depression. Two specific types of commonly occurring dermatoses-neurotic excoriations and dermatitis artefacta-are reviewed in this article. The major distinction of these disorders centers on whether the patient can admit to self-mutilation. Because of the difficulties in dermatitis artefacta with insight and body-image, it has been compared with anorexia nervosa. Often, dermatitis artefacta coexists with anorexia nervosa. In both disorders, neurotic excoriations and dermatitis artefacta, the personality style tends to be introverted with emotional immaturity. These patients have difficulty when they are under stress; the problem is compounded because of poor communication skills. Pharmacotherapy is of limited usefulness, and psychotherapy is often times hindered by strong resistance to exploring long-standing emotional issues. Once an alliance is established with the therapist, however, these issues may be examined. Prognosis is variable but does seem to directly correlate with the duration of the illness. Young individuals may experience alleviation of symptoms after one session of psychotherapy, whereas older patients may never have resolution. Dermatologic abuse involving psychosis has many presentations; one of the most common involves infestation. Organic causes must always be excluded as part of the differential diagnosis. In schizophrenia, this presentation has one of the highest incidences of suicide.(ABSTRACT TRUNCATED AT 250 WORDS)

Conflict, Psychological↗

Biochemical effects induced by REM sleep deprivation in naive and in D-amphetamine treated rats.

The neurochemical dysfunction present in patients showing self-mutilating behavior (SMB) is not well understood. In animal models, rapid eye movement (REM) sleep deprivation enhances the SMB induced by the chronic administration of d-amphetamine. To understand the mechanism underlying these effects the levels of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were measured in REM sleep deprived only, and in REM sleep deprived and d-amphetamine treated rats. DA levels were elevated (31%) after REM sleep deprivation (48 h) in the neostriatum and the cerebral cortex (33%), while the levels of NA and 5-HT remained constant. A 6-day treatment with d-amphetamine (7.5 mg/kg; i.p.) failed to affect, in REM sleep deprived rats, DA, NA and 5-HT levels. It was also found that REM sleep deprivation had no effects on the d-amphetamine induced [3H]DA release from slices of the same regions. Our results suggests that dopaminergic mechanisms are involved in the effects of REM sleep deprivation on SMB.

Animals↗