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delta opioid receptor modulation of several voltage-dependent Ca(2+) currents in rat sensory neurons.

Endogenous enkephalins and delta opiates affect sensory function and pain sensation by inhibiting synaptic transmission in sensory circuits via delta opioid receptors (DORs). DORs have long been suspected of mediating these effects by modulating voltage-dependent Ca(2+) entry in primary sensory neurons. However, not only has this hypothesis never been validated in these cells, but in fact several previous studies have only turned up negative results. By using whole-cell current recordings, we show that the delta enkephalin analog [D-Ala(2), D-Leu(5)]-enkephalin (DADLE) inhibits, via DORs, L-, N-, P-, and Q-high voltage-activated Ca(2+) channel currents in cultured rat dorsal root ganglion (DRG) neurons. The percentage of responding cells was remarkably high (75%) within a novel subpopulation of substance P-containing neurons compared with the other cells (18-35%). DADLE (1 microM) inhibited 32% of the total barium current through calcium channels (I(Ba)). A delta (naltrindole, 1 microM), but not a mu (beta-funaltrexamine, 5 microM), antagonist prevented the DADLE response, whereas a DOR-2 subtype (deltorphin-II, 100 nM), but not a DOR-1 (DPDPE, 1 microM), agonist mimicked the response. L-, N-, P-, and Q-type currents contributed, on average, 18, 48, 14, and 16% to the total I(Ba) and 19, 50, 26, and 20% to the DADLE-sensitive current, respectively. The drug-insensitive R-type current component was not affected by the agonist. This work represents the first demonstration that DORs modulate Ca(2+) entry in sensory neurons and suggests that delta opioids could affect diverse Ca(2+)-dependent processes linked to Ca(2+) influx through different high-voltage-activated channel types.

Animals↗

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open up new perspectives in the coming millennium.

Amputation, Surgical↗

[Hand transplantation and implantation of nerve chips. New developments within hand surgery].

Injuries and diseases of the hand naturally have an enormous impact on hand function and on quality of life, both occupational and social. The majority of hand-injury patients are under 30 years of age. Hand surgery, an established specialty in Sweden since 1969, is of great importance in terms of clinical developments, education and research. In the coming decade, scientific and clinical advances are to be expected in several fields such as nerve injuries including brachial plexus lesion, microsurgery, flexor tendon injuries and tendon transfer. Bioimplant research and new advances at the biotechnological interface will yield new options in nerve reconstruction, microchip implants in the nervous system, and the restoration of muscle-tendon function following injury. Artificial limbs with advanced motor and sensory functions will be important future aids in the rehabilitation of amputees. Transplantation of human hands is another promising reconstructive procedure which may open iup new perspectives in the coming millennium.

Amputation, Surgical↗

[The pyramidal tract: new pathways].

OBJECTIVE: To review some anatomofunctional aspects of the pyramidal tract which are relevant in clinical practice, especially the newer concepts. DEVELOPMENT: a) Although the motor function is best known, the pyramidal tract also has sensory functions, modulating the transmission of impulses in the spinal cord. In fact, motor function is a recent acquisition on the evolutionary scale. b) Other descending pathways, such as the cortico reticulospinal path, participate in voluntary movements. However, the pyramidal pathway is necessary for fine movements of the hand. c) Most of the pyramidal fibres control movements of the contralateral side of the body, but there are a few fibres which do not cross to the other side and play a part in ipsilateral body movements. These fibres seem to contribute to motor recovery following a brain lesion. d) Classically it is recognized that the motor cortex and pyramidal fibres follow a somatotopical distribution. Nevertheless territories corresponding to different parts of the body are superimposed to a considerable extent and may be modified on very diverse occasions. e) Experimentally it has been proved that a circumscribed lesion of the pyramidal pathway does not cause hyper reflexia or spasticity. The hyper reflexia and spasticity habitually seen in patients with pyramidal syndrome is due to lesions of other descending pathways. CONCLUSION: The pyramidal tract is anatomically and functionally related to other nerve structures and its activity is therefore integrated within the nervous system.

Animals↗

[Physiological and clinical recall on equilibrium disorders].

Static and dynamic equilibrium (posture and gait) is indispensable for a normal behavior in human. Its mechanisms are nearly the same in superior species and in man, but humans are the only ones to have acquired exclusively biped upright position and gait. Equilibrium is a sensory function involving 3 sub systems: visual, vestibular and sensori-motor (proprioceptive), controlled by cerebellum and cerebral structures. Information coming from those 3 sub systems must be concordant. In case of discordance, the patient is in a state of sensory conflict. This conflict can induce disequilibrium or true vertigo. After a recall on equilibrium, the authors report the results of an epidemiologic study upon 5298 patients suffering of balance disorders and treated by an alpha-blocker: nicergoline (30 mg/day during 6 months).

Humans↗

Evoked brain potentials and disability in brain-damaged patients.

Various measures of evoked brain potential abnormality (EPA) were correlated with disability ratings (DR) for 35 brain-damaged patients. EPA data consisted of judgements of abnormality of ipsilateral, contralateral and bilateral responses to auditory and visual stimuli reflecting activity in the brain stem, subcortex and cortex. DR data were obtained from a scale developed for this study to quantize and categorize patients with a wide range of disabilities from coma to normal functioning. EPA scores based on visual and auditory cortical responses showed significantly positive correlations with degree of disability. Visual response correlation was .49, auditory .38 and combined visual and auditory .51. It was concluded that EPA measures can reflect disability independently of clinical information. They are useful in assessing brain function in general and, specifically, in assessing impairment of sensory function. The evoked potential technique was particularly useful in patients who were not able to participate fully in their own examination. There were indications that the technique may also be valuable in monitoring progress and in predicting clinical outcome in brain-damaged patients.

Adult↗

Reflex modification and the detection of toxicant-induced auditory dysfunction.

There are numerous environmental chemicals that adversely impact sensory functioning in exposed populations. Test methods are needed that can rapidly and efficiently assess the potential of chemicals to induce sensory toxicity. Reflex modification of the startle response is a technique that provides rapid, objective and quantitative assessments of sensorimotor function. This procedure has been shown to be sensitive to a variety of neurotoxic compounds. Reflex modification can also provide independent estimates of chemical-induced alterations in both sensory and motor function. Future efforts should focus on expanding the use of this procedure in both the identification and characterization of neurotoxic chemicals.

Animals↗

Lower extremity paralysis after operative laparoscopy from conversion disorder. A case report.

BACKGROUND: Neurologic complications are rarely associated with laparoscopic procedures, and most nerve injuries are transient palsies. We present the first case of paraplegia following gynecologic laparoscopy. CASE: A 34-year-old woman, gravida 2, para 0-1-1-0, with long-standing infertility, underwent an uncomplicated laparoscopic ovarian cystectomy for a persistent ovarian cystadenoma. In the immediate postoperative period, the patient developed bilateral lower extremity paralysis. She regained her sensorimotor function in one extremity within hours, while both motor and sensory functions, but not proprioception, were deficient in the other extremity in a pattern of distribution that was inconsistent and paradoxical. Diagnostic studies to evaluate the patient's central and peripheral nervous systems and evoked sensory potentials were all normal. The patient's indifference to her persistent yet paradoxical neurologic deficits was a clue to her diagnosis. In the absence of an organic lesion to account for the patient's symptoms, the diagnosis of conversion disorder was made. CONCLUSION: Neurologic complications following laparoscopy are rare, generally involving nerve palsies from local injury. This is the first report of lower extremity paralysis after laparoscopy. Although conversion disorder is rare, it may occur in the gynecologic setting owing to its prevalence in women and especially in the presence of underlying affective disorders.

Adult↗

The sensational contributions of Erik Moberg.

Erik Moberg is the father of functional sensory testing. During the past three decades, his research into quantitative testing of hand sensibility has provided the insight to bring us from classic academic tests (permitting localisation of lesions within the central nervous system) to clinical capability of restoring sensation to the hand. He introduced the Ninhydrin test to document objectively innervation. He defined hand function as precision-sensory and gross-sensory grips. He correlated Weber two-point discrimination with hand function. He introduced the pick-up test to document hand function. He coined the term "tactile gnosis". He hypothesised that proprioception is principally due to skin, not joint, afferents. He classified the tetraplegic hand according to its combined sensory and motor capacity. He set the standard for sensory recovery after primary nerve repair, relating recovered two-point discrimination to age (Onne's line) and he inspired the present generation of researchers to quantify their own studies of sensation.

General Surgery↗

Variability in function measurements of three sensory foot nerves in neuropathic diabetic patients.

We have examined the variability in function measurements of three sensory foot nerves in neuropathic diabetic patients and have compared them to measurements from healthy non-diabetic subjects. Sixty-six healthy, non-diabetic subjects (30 (45%) males, mean age 56 years (range, 21-84 years)) and 61 age and sex matched diabetic patients (33 (54%) males, mean age 55 years (range, 34-78 years) Type 1 diabetes mellitus (DM), mean duration of DM 24 years (range, 2-48 years)) were tested. Current perception threshold (CPT) at 250 Hz was employed to test the sensory function of three nerves: superficial peroneal, sural and posterior tibial. The vibration perception threshold, (VPT) and the cutaneous perception threshold (CCPT) were also assessed at the great toe. According to the results of the neuropathy disability score (NDS), mild neuropathy was present in 8 (13%) patients, moderate in 33 (54%) and severe in 20 (33%). In both groups the CPT of the posterior tibial nerve was higher than the other two nerves (P < 0.0001) while no difference was found between the superficial peroneal and sural nerves (P = NS). CPT was different between the two feet at the superficial peroneal nerve in 39 (64%) diabetic patients and 34 (52%) controls (P = NS), at the sural nerve in 40 (65%) and 45 (68%) (P = NS), and at the posterior tibial in 36 (59%) and 33 (50%), respectively (P = NS). VPT was different by more than 10% at the great toes in 26 (43%) diabetic subjects and CCPT in 21 (34%). We conclude that although there is variation in sensory nerve function tests in diabetic patients this is similar to that noticed in healthy subjects. The great variability of all quantitative sensory testing indicates that more than one site should be tested.

Adolescent↗

Modification of visceral sensitivity and pain in irritable bowel syndrome by 5-HT3 antagonism (ondansetron).

Intrinsic neurons containing serotonin (5-HT) are involved in the regulation of gastrointestinal motor function and are also thought to be important in the modulation of visceral sensory function. We have evaluated the effect of a specific 5-HT3 antagonist (ondansetron, O) on visceral sensation and rectal compliance in a randomized, double-blind, cross-over, placebo (P) controlled study of O 16 mg 3 times/day, in healthy volunteers and patients with irritable bowel syndrome (IBS). Symptoms were also evaluated in the latter group. A 2-week run-in period was followed by two 2-week treatment arms of P and O, separated by a 2-week wash-out period. Twelve healthy subjects and 9 patients with IBS were recruited. Assessment was by daily symptom and bowel function diary, and physiological tests of anal manometry, rectal sensory testing to distension and electrical stimulation, and rectal compliance. Ten healthy subjects completed the entire study, and 6 IBS patients completed the diary card evaluation, including 5 who also completed the physiological evaluation. O caused significantly (p < 0.01) firmer stools when considering both subject groups together. In the healthy subjects no physiological parameters were altered by O. In IBS patients the rectal sensory threshold to electrical stimulation tended to increase with O (20 vs. 28 mA, P vs. O, median, p = 0.06) while the urge (80 vs. 60 ml, p = 0.05) and maximum tolerated volumes (130 vs. 90, p = 0.03) to distension tended to decrease with O. Patients with IBS experienced significantly fewer daily episodes of pain while on O (2 vs. 1, p = 0.03). Serotonin-3 antagonism (O) causes firmer bowel actions in all subjects, and may affect gut sensitivity and pain in patients with IBS.

Adult↗

[Results of surgical treatment for traumatic injury of upper extremity peripheral nerves taken from personal material].

A series of 52 patients with peripheral nerve injury, treated operatively is presented. Motor function has been assessed according to Highet (MO-M5). Sensory function has been evaluated according to Nicholson and Seddon (S0-S4). An attempt to show decisive factors for successful peripheral nerve reconstruction. Clinical analysis proved surgical technique, modified with experience gained influences the final result remarkably. Imposition of microsurgical techniques and instrumentation as well as operative microscopy improved efficacy of the treatment. Delay of final reconstruction worsens ultimate outcome. Age of the patient and coexisting injury of the skin, tendons and bone that change conditions of nerve regeneration are also important. The longer the skin nerve graft is the worse motor and sensory recovery.

Adolescent↗

Neuropeptide expression in rat paraventricular hypothalamic neurons that project to the spinal cord.

The paraventricular hypothalamic nucleus (PVH) exerts many of its regulatory functions through projections to spinal cord neurons that control autonomic and sensory functions. By using in situ hybridization histochemistry in combination with retrograde tract tracing, we analyzed the peptide expression among neurons in the rat PVH that send axons to the spinal cord. Projection neurons were labeled by immunohistochemical detection of retrogradely transported cholera toxin subunit B, and radiolabeled long riboprobes were used to identify neurons containing dynorphin, enkephalin, or oxytocin mRNA. Of the spinally projecting neurons in the PVH, approximately 40% expressed dynorphin mRNA, 40% expressed oxytocin mRNA, and 20% expressed enkephalin mRNA. Taken together with our previous findings on the distribution of vasopressin-expressing neurons in the PVH (Hallbeck and Blomqvist [1999] J. Comp. Neurol. 411:201-211), the results demonstrated that the different PVH subdivisions display distinct peptide expression patterns among the spinal cord-projecting neurons. Thus, the lateral parvocellular subdivision contained large numbers of spinal cord-projecting neurons that express any of the four investigated peptides, whereas the ventral part of the medial parvocellular subdivision displayed a strong preponderance for dynorphin- and vasopressin-expressing cells. The dorsal parvocellular subdivision almost exclusively contained dynorphin- and oxytocin-expressing spinal cord-projecting neurons. This parcellation of the peptide-expressing neurons suggested a functional diversity among the spinal cord-projecting subdivisions of the PVH that provide an anatomic basis for its various and distinct influences on autonomic and sensory processing at the spinal level.

Animals↗

Effects of lesions invading the postcentral gyrus on somatosensory thresholds on the face.

Patients with unilateral removals from either the parietal, frontal or temporal lobe and normal control subjects were examined on three tests of tactile sensibility. The patients with surgical excisions from the parietal lobe were subdivided into two groups: those whose lesions invaded the face area in the primary sensory cortex and those whose lesions spared this area. A significant percentage of patients with lesions that invaded the face area had mild to severe sensory deficits on the side of the face contralateral to the lesion. A much smaller number of patients had deficits on the ipsilateral side. Lesions to the face area in the primary sensory cortex were, however, associated with a lower incidence of severe and persistent sensory deficits when compared to previous results on the effects of lesions to the hand area on the sensory capacity of the hand. These results suggest that there is some preservation of sensory function after damage to the face area in the primary sensory cortex, presumably due to the bilateral representation of the face.

Adolescent↗

Dynamic organization of intersensory function.

Issues related to infant intersensory functioning are reviewed. The argument is offered that limitations of sensory inputs during early stages of development are necessary and provide structure and organization which determine behavioural characteristics at later stages. It is also suggested that infant organisms respond to the intensity of stimulation rather than organizational characteristics and that this is responsible for the form of sensory equivalence apparent during early development. A scheme for the investigation of sources of intersensory organization is presented which involves a prospective analysis of how consideration of the times of onset of sensory functions helps us to understand intra- and intersensory development. The advantages of this experimental approach are outlined.

Arousal↗

Cholangiocyte cilia detect changes in luminal fluid flow and transmit them into intracellular Ca2+ and cAMP signaling.

BACKGROUND & AIMS: Cholangiocytes have primary cilia extending from the apical plasma membrane into the ductal lumen. While the physiologic significance of cholangiocyte cilia is unknown, studies in renal epithelia suggest that primary cilia possess sensory functions. Here, we tested the hypothesis that cholangiocyte cilia are sensory organelles that detect and transmit luminal bile flow stimuli into intracellular Ca2+ ([Ca2+]i) and adenosine 3',5'-cyclic monophosphate (cAMP) signaling. METHODS: Scanning electron microscopy, transmission electron microscopy, and immunofluorescent confocal microscopy of rat isolated intrahepatic bile duct units (IBDUs) were used to detect and characterize cholangiocyte cilia. The fluid flow-induced changes in Ca2+ and cAMP levels in cholangiocytes of microperfused IBDUs were detected by epifluorescence microscopy and a fluorescence assay, respectively. RESULTS: In microperfused IBDUs, luminal fluid flow induced an increase in [Ca2+]i and caused suppression of the forskolin-stimulated cAMP increase. The fluid flow-induced changes in [Ca2+]i and cAMP levels were significantly reduced or abolished when cilia were removed by chloral hydrate or when ciliary-associated proteins polycystin-1 (a mechanoreceptor), polycystin-2 (a Ca2+ channel), and the Ca2+-inhibitable adenylyl cyclase isoform 6 were individually down-regulated by small interfering RNAs. CONCLUSIONS: Cholangiocyte cilia are sensory organelles containing polycystin-1, polycystin-2, and adenylyl cyclase isoform 6 through which luminal fluid flow affects both [Ca2+]i and cAMP signaling in the cell. The data suggest a new model for regulation of ductal bile secretion involving cholangiocyte cilia.

Animals↗

Iatrogenic nerve lesions of the upper extremity.

Thirty-three patients are presented who suffer from iatrogenic nerve injury of the upper extremity. Depending on the nature, duration, and degree of nerve injury, we performed neurolysis (16), direct nerve coaptation (4), and nerve grafting (13). Fourteen (70%) of 20 patients presenting with motor nerve injury achieved motor function against resistance. In 26 of 30 patients (87%) with sensory nerve involvement, at least some superficial sensory function was restored. Surgeons should be familiar with clinical and electroneurophysiological tests for early diagnosis of iatrogenic nerve injuries to allow early intervention for maximal nerve recovery.

Adolescent↗

Functional relationship between human rolandic oscillations and motor cortical excitability: an MEG study.

Synchronization and desynchronization of the neural rhythm in the brain play an important role in the orchestration of perception, motor action and conscious experience. Based on the results of electrocorticographic and magnetoencephalographic (MEG) recordings, it has been considered that human rolandic oscillations originate in the anterior bank of the central sulcus (20-Hz rhythm) and the postcentral cortex (10-Hz rhythm): the 20-Hz oscillation is closely related to motor function, while the 10-Hz rhythm is attributed mainly to sensory function. To test whether the rolandic oscillations are functionally relevant to the motor cortical excitability, we examined effects of 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the left primary motor cortex (M1) on movement-related changes of the rolandic oscillations in 12 normal subjects. MEG data recorded during brisk extension of the right index finger in two different sessions (with and without rTMS conditioning) were compared. Motor-evoked potential (MEP) of the right hand muscle was also measured before and after rTMS to assess the motor cortical excitability. We found that 1-Hz rTMS over M1 significantly reduced the movement-related rebound of the 20-Hz oscillation in association with decreased motor cortical excitability. In particular, movement-related rebound of the 20-Hz rhythm was closely tied with motor cortical excitability. These findings further strengthen the notion of functional relevance of 20-Hz cortical oscillation to motor cortical excitability. In the framework of previous studies, the decrease in movement-related rebound may be regarded as a compensatory reaction to the inhibited cortical activity.

Adult↗