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Cocaine- and amphetamine-related transcript peptide and somatostatin in rat intracardiac ganglia.

The distribution of somatostatin and cocaine and amphetamine-regulated transcript (CART) was investigated in rat intracardiac ganglia. Somatostatin immunoreactivity was only present in nerve terminals, always colocalised with choline acetyltransferase immunoreactivity, surrounding approximately 10% of intracardiac neurons. Somatostatin-immunoreactive terminals particularly targeted intrinsic cardiac neurons that were immunoreactive for calbindin. Somatostatin was also present in sympathetic cholinergic neurons in the stellate ganglia, but could not be detected in neurons of the nucleus ambiguus and dorsal motor nucleus of the vagus in the brainstem. CART immunoreactivity was present in 46% of intracardiac neuronal somata, including those that expressed either NOS or calbindin immunoreactivity but was never present in terminals forming pericellular baskets around intracardiac neurons. CART immunoreactivity was absent from sympathetic cell bodies in the stellate ganglia, but was present in nerve terminals around sympathetic neurons. Based on the results of this study, additional chemical diversity was identified among elements of the rat cardiac nervous system that may define neural pathways of different function.

Animals↗

A thoracoscopic view of the nerve of Kuntz.

The nerve of Kuntz and alternate neural pathways (ANPs) have long been considered crucial for upper limb sympathetic supply. However, at thoracoscopy, these structures are neither consistently identified nor searched for. This is probably reflective of the effectiveness of an isolated second thoracic ganglionectomy for upper limb sympathectomy. We present the case of a 19-year-old male who underwent a second thoracic ganglionectomy for palmar hyperhidrosis. On the left side, approximately 2.5 cm lateral to the typically located sympathetic chain, a filamentous structure (one-quarter the diameter of the sympathetic chain), identified as the nerve of Kuntz, was noted coursing across the neck of the second rib.

Adult↗

[Relevance of nerve blocks in treating and diagnosing low back pain--is the quality decisive?].

Diagnostic nerve blocks: The popularity of neural blockade as a diagnostic tool in painful conditions, especially in the spine, is due to features like the unspecific character of spinal pain, the irrelevance of radiological findings and the purely subjective character of pain. It is said that apart from specific causes of pain and clear radicular involvement with obvious neurological deficits and corresponding findings of a prolapsed disc in MRI or CT pictures, a diagnosis of the anatomical cause of the pain can only be established if invasive tests are used [5]. These include zygapophyseal joint blocks, sacroiliacal joint blocks, disc stimulation and nerve root blocks. Under controlled conditions, it has been shown that among patients with chronic nonradicular low back pain, some 10-15% have zygapophyseal joint pain [58], some 15-20% have sacroiliacal joint pain [36, 59] and 40% have pain from internal disc disruption [60]. The diagnostic use of neural blockade rests on three premises. First, pathology causing pain is located in an exact peripheral location, and impulses from this site travel via a unique and consistent neural root. Second, injection of local aneasthetic totally abolishes sensory function of intended nerves and does not affect other nerves. Third, relief of pain after local anaesthetic block is attributable solely to block of the target afferent neural pathway. The validity of these assumptions is limited by complexities of anatomy, physiology, and psychology of pain perception and the effect of local anaesthetics on impulse conduction [28]. Facet joints: The prevalence of zygapophyseal joint pain among patients with low back pain seems to be between 15% and 40% [62], but apparently only 7% of patients have pure facet pain [8, 29]. Facet blockade is achieved either by injection of local anaesthetic into the joint space or around the medial branches of the posterior medial rami of the spinal nerves that innervate the joint. There are several problems with intraarticular facet injections, mainly failure to enter the joint capsule and rupture of the capsule during the injection [11]. There is no physiological means to test the adaequacy of medial nerve block, because the lower branches have no cutaneous innervation. Medial ramus blocks (for one joint two nerves have to be infiltrated) are as effective as intraarticular joint blocks [37]. Reproducibility of the test is not high, the specifity is only 65% [61]. For diagnosis of facet pain fluoroscopic control is always necessary as in the other diagnostic blocks. Sacroiliacal joint: Definitely the sacroiliacal joint can be the source of low back pain. Stimulation of the joint by injection in subjects without pain produces pain in the buttock, in the posterior thigh and the knee. There are many clinical tests which confirm the diagnosis, but the interrater reliability is moderate [53]. Intraarticular injection can be achieved in the lower part of the joint with fluoroscopic guidance only, but an accurate intraarticular injection, which is confirmed by contrast medium, even at this place is often difficult. It is not clear whether intraarticular spread is necessary to achieve efficacy. Discography: Two primary syndromes concerning the ventral compartment have been described: anular fissures of the disc and instability of the motion segment. In the syndrome of anular tear, leakage of nucleus pulposus material into the anulus fibrosus is considered to be the source of pain. The studies of Vaharanta [71] and Moneta [41] show a clear and significant correlation between disc pain and grade 3 fissures of the anulus fibrosus. intervertebral discs are difficult to anaesthetize. Intradiskal injections of local anaesthetics may succeed in relieving the patient's pain, but such injections are liable to yield false negative results if the injected agent fails to adequately infiltrate the nerve endings in the outer anulus fibrosus that mediate the patient's pain. In the majority of cases MRI provide adaequate information, but discography may be superior in early stages of anular tear and in clarifying the relation between imaging data and pain [71]. Selective spinal nerve injection: In patients with complicated radiculopathy, the contribution of root inflammation to pain may not be certain, or the level of pathology may be unclear. Diagnostic root blocks are indicated in the following situations: atypical topography of radicular pain, disc prolapses or central spinal stenosis at more than one level and monoradicular pain, lateral spinal stenosis, postnucleotomysyndrome. Injection of individual spinal nerves by paravertebral approach has to be used to elucidate the mechanism and source of pain in this unclear situations. The premise is that needle contact will identify the nerve that produces the patient's characteristic pain and that local anaesthetic delivered to the pathogenic nerve will be uniquely analgesic. Often, this method is used for surgical planning, such as determining the site of foraminotomy. All diagnostic nerve root blocks have to be done under fluoroscopic guidance. Pain relief with blockade of a spinal nerve cannot distinguish between pathology of the proximal nerve in the intervertebral foramen or pain transmitted from distal sites by that nerve. Besides, the tissue injury in the nerve's distribution and neuropathic pain (for instance as a result of root injury) likewise would be relieved by a proximal block of the nerve. Satisfactory needle placement could not be achieved in 10% of patient's at L4, 15% at L5 and 30% at S1 [28]. The positive predictive value of indicated radiculopathy confirmed by surgery ranged between 87-100% [14, 22]. The negative predictive value is poorly studied, because few patients in the negative test group had surgery. Negative predictive values were 27% and 38% of the small number of patients operated on despite a negative test. Only one prospective study was published, which showed a positive predictive value of 95% and an untested negative predictive value [66]. Some studies repeatedly demonstrated that pain relief by nerve root block does not predict success by neuroablative procedures, neither by dorsal rhyzotomy nor by dorsal gangliectomy [46]. Therapeutic nerve blocks - facet joints: Intraarticular injection of steroids offer no greater benefit than injections of normal saline [8, 15] and long lasting success is lacking. In this case, a denervation of the medial branches can be considered. To date three randomized controlled studies of radiofrequency facet denervation have been published. One study [20] reported only modest outcomes and its results remained inconclusive, another study [72] with a double blind controlled design showed some effects in a small selected group of patients (adjusted odds ratio 4.8) 3, 6 and 12 months after treatment, concerning not only reduction of pain but alleviating functional disability also. The third study (34a) showed no effect 3 months after treatment. Discogenic pain: Intradiscal radiofrequency lesions, intradiscal injections of steroids and phenol have been advocated, but there are no well controlled studies. Just recently, intradiscal lesion and denervation of the anulus has been described with promising results, but a randomized controlled study is lacking up to now [31, 55]. Epidural Steroids: Steroids relieve pain by reducing inflammation and by blocking transmission of nociceptive C-fiber input. Koes et al. [33] reviewed the randomized trials of epidural steroids: To date, 15 trials have been performed to evaluate the efficacy, 11 of which showed method scores of 50 points (from 100) ore more. The trials showed inconsistent results of epidural injections. Of the 15 trials, 8 reported positive results and 7 others reported negative results. Consequently the efficacy of epidural steroid injections has not yet been established. The benefits of epidural steroid injections seem to be of short duration only. Future efficacy studies, which are clearly needed, should take into account the apparent methological shortcomings. Furthermore, it is unclear which patients benefit from these injections. In our hands the injection technique can be much improved by fluoroscopic guidance of the needle, with a prone position of the patient, and lateral injection at the relevant level and with a small volume (1-2 ml) and low dose of corticosteroid (20 mg triamcinolone in the case of a monoradicular pain, for example). In the case of epidural adhesions in postoperative radicular pain [50], the study of Heafner showed that the additional effect of hyaloronidase and hypertonic saline to steroids was minimal. In our hands there was no effect in chronic radicular pain 3 months after the injection.

Humans↗

Distress before chemotherapy predicts delayed but not acute nausea.

INTRODUCTION: Posttreatment nausea (PTN) is a common side effect of cytotoxic cancer chemotherapy. Previous retrospective research has suggested that the severity of PTN may be, in part, related to pretreatment psychological factors (e.g., emotional distress and expectations for nausea). MATERIALS AND METHODS: The purpose of the present study was to examine these relationships prospectively, with distress and nausea expectations assessed by validated self-report measures completed in the clinic before the participants' first outpatient treatment infusion and with PTN (0-100) assessed by end-of-day diaries completed at home on each of the first 5 days after treatment. The participants were chemotherapy-naive women (N=56) scheduled for standard adjuvant treatment for stage I-II breast cancer (mean age=45.6 years). PTN was evaluated for acute (days 0-1) and delayed (days 2-5) responses. RESULTS: The results revealed a significant relationship between pretreatment distress and the severity of the patients' subsequent delayed nausea (p<0.007) but not a relationship with acute PTN (p<0.19). No significant relationships were seen between expectations and PTN. However, there was evidence of an additive effect of nausea expectations and distress, with the highest levels of delayed PTN seen in patients with both expectations and higher distress before treatment. The results suggest a selective effect of pre-infusion psychological variables on the delayed phase of nausea after chemotherapy, consistent with an emerging view that the different phases of nausea are mediated by different neural pathways. CONCLUSION: Future research should examine the possibility that delayed nausea, which the literature suggests is more resistant to antiemetic drugs than acute nausea, might be responsive to psychological interventions before initial treatments.

Adult↗

Reliability of electrophysiologic anal tests in predicting the outcome of sacral nerve modulation for fecal incontinence.

INTRODUCTION: Sacral nerve modulation has been demonstrated to be a new efficacious treatment for fecal incontinence. The effectiveness of the procedure is preliminarily tested by means of a peripheral nerve evaluation. Integrity of the sacral neural pathway is generally believed to be a necessary condition for a good response, but no data are available to confirm whether electrophysiologic anal tests are predictive of the clinical outcome of the peripheral nerve evaluation. METHODS: Eighty-two incontinent patients underwent the peripheral nerve evaluation after full evaluation of the anorectal physiology. Univariate analysis was performed, and the positive predictive value, sensitivity, and specificity were calculated for each of the tests. RESULTS: Forty-six patients had successful results to the peripheral nerve evaluation and were subjected to permanent implant of a sacral electrostimulator. Anal sphincter electromyography had been performed in 60 patients, whereas pudendal nerve terminal motor latency had been assessed in 68 and evoked sacral potentials in 29 patients. Anal electromyography was statistically related to the outcome of the peripheral nerve evaluation ( P = 0.0004) with a positive predictive value of 81 percent, a sensitivity of 44 percent, and a specificity of 81 percent. Pudendal nerve terminal motor latency on the right side did not correlate with the outcome, but left pudendal nerve terminal motor latency was weakly correlated ( P = 0.02), although both tests had a low positive predicting value and sensitivity vs. good specificity. Evoked sacral potentials did not correlate with the outcome and had a low positive predictive value, sensitivity, and specificity. CONCLUSIONS: Simple anal sphincter electromyography can predict the outcome of the peripheral nerve evaluation with good positive predictive value and specificity in patients with fecal incontinence. Other, more expensive, electrophysiologic anal tests do not add further prognostic information.

Aged↗

Nocturnal penile tumescence is diminished but not ablated in postproctectomy impotence.

PURPOSE: We aimed to assess objectively the integrity of the parasympathetic neural pathway that controls the inflow choke vessels to the corpora cavernosa in a group of male patients with postproctectomy erectile dysfunction. METHODS: The study group was male patients with erectile dysfunction after proctectomy for rectal cancer and inflammatory bowel disease identified by sexual function questionnaire. The group underwent two consecutive nights of home nocturnal penile tumescence monitoring with the Nocturnal Electrobioimpedance Volumetric Assessment device. The control group was also monitored. It comprised preoperative potent patients with rectal cancer and inflammatory bowel disease who had not yet undergone a variety of surgical procedures. Demographics and nocturnal penile tumescence parameters were recorded, including number, duration, and percentage increase in penile volume of tumescent events. RESULTS: Thirty-four impotent study group and 28 potent control group patients underwent nocturnal penile tumescence monitoring. The groups were well matched for mean age (difference, 1.4 years; 95 percent confidence interval, -5.8 to 8.6 years) and proportion with rectal cancer (difference, 6 percent; 95 percent confidence interval, -1 to 13 percent). The number of nocturnal penile tumescent events was greater for the potent group than for the control group (mean rank, 40.4 vs. 24.2; P = 0.0004). There was no significant difference between the mean duration (difference, 2.6 minutes; mean rank, 27.9 vs. 34.4; P = 0.16) or the mean penile volume increase (difference, 5.4 percent increase; mean rank, 30.6 vs. 32.6; P = 0.66) for tumescent events between the study and control groups. Mean age was significantly higher in complete than in partial impotence (60.9 vs. 53.1 years; difference, 7.8 years; 95 percent confidence interval, 0.1 to 15.5 years). There was a nonsignificant trend to a lower mean number of tumescence events among sildenafil responders than among nonresponders (3.5 vs. 4.8 events; mean rank, 11.2 vs. 17.3; P = 0.14). CONCLUSION: Nocturnal penile tumescence activity is diminished but not ablated by the trauma of surgical dissection. This suggests that some of the cavernous nerves that govern inflow to the corpora cavernosa are intact after surgery and that the nerve lesion responsible for erectile dysfunction is partial, and it explains why the response to sildenafil in such patients is surprisingly high.

Adult↗

Laterality biases to chimeric faces in Asperger syndrome: what is 'right' about face-processing?

People show a left visual field (LVF) bias for faces, i.e., involving the right hemisphere of the brain. Lesion and neuroimaging studies confirm the importance of the right-hemisphere and suggest separable neural pathways for processing facial identity vs. emotions. We investigated the hemispheric processing of faces in adults with and without Asperger syndrome (AS) using facial emotion and identity chimeric tasks. Controls showed an LVF bias in both tasks, but no perceptual bias in a non-social control task. The AS group showed an LVF bias during both tasks, however the bias was reduced in the identity condition. Further, the AS group showed an LVF bias in the non-social condition. These results show a differential pattern of hemispheric processing of faces in AS.

Adult↗

Selective Spinal Injections for Lower Back Pain.

Tremendous progress has been made in the understanding of neural pathways and tissues involved in back pain, and new treatment techniques for back pain have evolved. This article focuses on a technique called epidural neuroplasty (lysis of epidural adhesions). Originally performed as a single-catheter technique using the caudal approach, this technique now features a number of variations. These variations include emphasis on anterior placement of the catheter tip, use of a transforaminal approach, and use of one or two catheters.

Journal Article↗

The genetics of alcoholism and alcohol abuse.

Twin studies have established that there are substantial genetic influences on alcoholism (0.5-0.6) in both men and women. Our knowledge of behaviors predisposing to alcoholism, including anxiety and impulsivity, is advancing rapidly through animal and human studies. Although alcoholism is often comorbid with other substance abuse and psychiatric disorders, recent studies have shown that, with the exception of nicotine, the heritability of alcoholism is largely substance-specific. Increasing understanding of the neurobiology of addiction has identified neural pathways in which genetic variation at candidate genes could influence vulnerability. Some functional variants of these genes have been identified. Recent linkage analyses in humans and rodents have pointed to genomic regions harboring genes that influence alcoholism. Refinement of clinical phenotypes and use of intermediate phenotypes will improve chances of gene identification. All these advances in the understanding of the genetics of alcoholism should facilitate the development of more accurately targeted therapies using molecular diagnostic approaches.

Alcoholism↗

Choosing the right medication for the treatment of alcoholism.

In the past decade, scientists have made important progress toward understanding the neurobiology underlying an alcohol disorder. This knowledge has led to the development of promising pharmacotherapies that target the neural pathways involved in the brain's reward center in such a way that the usual treatment response (via counseling) is substantially improved upon. There are now four US Food and Drug Administration (FDA)-approved pharmacotherapies for the treatment of alcohol dependence: disulfiram (Antabuse; Odyssey Pharmaceuticals, East Hanover, NJ), oral naltrexone (ReVia; Barr Pharmaceuticals, Inc., Pomona, NY), acamprosate (Campral; Forest Laboratories, Inc., New York, NY), and, as of April 2006, an extended-release (30-day) injectable suspension formulation of naltrexone (Vivitrol; Alkermes, Inc., Cambridge, MA). Other types of medications (eg, topiramate and quetiapine) are currently under investigation for the treatment of alcohol dependence. Research also has provided insights into best practices for prescribing the available medications. This report reviews the latest innovations in pharmacotherapy for the treatment of alcohol dependence, focusing on FDA-approved medications presently available to the treatment community.

Acamprosate↗

Esophageal motility disorders (distal esophageal spasm, nutcracker esophagus, and hypertensive lower esophageal sphincter): modern management.

The group of hypercontractile esophageal motility disorders includes distal esophageal spasm (DES), nutcracker esophagus (NE), and hypertensive lower esophageal sphincter (LES). The clinical relevance of these abnormalities identified during esophageal manometry is debated, and their management can be challenging. Hypercontractile esophageal motility abnormalities are defined through specific manometric criteria. Current pathophysiologic concepts for these abnormalities include defects in the nitronergic neural pathways and imbalances between the cholinergic and nitronergic pathway. Proposed treatments for NE, DES, and hypertensive LES include proton-pump inhibitors, nitrates, calcium channel blockers, phosphodiasterase inhibitors, and tricyclic antidepressants or serotonin reuptake inhibitors. Small case series reported benefits after botulinum toxin injections, dilatations, and myotomies. The optional management of esophageal spasm, NE, and hypertensive LES is still debated. Treatment recommendations are based on controlled studies with small numbers of patients or on case series. Medical treatment, including acid suppression, smooth muscle relaxants, and visceral analgesics, should be tried first. In nonresponding patients, botulinum toxin injections or balloon dilatations can be tried. Pneumatic dilatations or myotomies should be regarded as last-option treatments for nonresponding patients.

Journal Article↗

The effect of hypothalamic lesions on the length of gestation in fetal sheep.

Twenty-nine sheep fetuses were subject to stereotaxic surgery at 106 to 110 days of gestation. Electrolytic lesions were placed bilaterally in the anterior hypothalamus. Sham-operated controls (n = 4) were delivered at 146.3 +/- 4.3 days. Of the fetuses with lesions, two were excluded because histologic confirmation of the lesion was not possible. Those fetuses with bilateral lesions of the suprachiasmatic nuclei (n = 4) were delivered at 148 +/- 10 days. In 10 animals with bilateral lesions of the paraventricular nuclei, delivery was significantly (p less than 0.0001) prolonged to at least 165.6 +/- 5.1 days. In nine animals with lesions not involving the endocrine hypothalamus, delivery was at 148.1 +/- 4.3 days. All animals that were delivered after 157 days (n = 9) had lesions including the paraventricular nuclei bilaterally (p less than 0.01). The adrenal glands of fetuses with prolonged gestation were normal in weight and light microscopic appearance. These observations demonstrate that fetal neural pathways involving the paraventricular nuclei are essential for parturition in the sheep. However, fetal adrenal growth can continue without such influences.

Adrenal Glands↗

Spontaneous return of function after surgical excision of the seventh cranial nerve in parotid tumor surgery.

Spontaneous return of function after surgical excision of the seventh cranial nerve in surgery of parotid tumors is not impossible. This seems to occur through the several existing neural pathways between the fifth and seventh cranial nerves. It is probable that voluntary motor impulses by reeducation find their way from the cortex through the fifth cranial nerve to the respective muscles.

Adult↗

Nerve terminal proteins of the rabbit visual relay nuclei identified by axonal transport and two-dimensional gel electrophoresis.

The proteins in nerve terminals can be uniquely identified by two-dimensional gel electrophoresis of proteins labeled during synthesis in the cell body and then transported intra-axonally to the terminals. We have explored the potential of the identification procedure by comparing the proteins which are transported from the retina to the lateral geniculate nucleus (LGN) and the superior colliculus (SC) of the rabbit. We have been able to identify between 150 and 200 proteins which ate common to both LGN and SC nerve terminals, very few of which are present at significantly different concentrations in one nucleus relative to the other. The similarity between proteins sent from the retina along two neural pathways subserving different functions illustrates the subtlety of biochemical changes that must underlie physiological differences. Only a small fraction of the labeled proteins are major proteins of the relay nuclei as judged by Coomassie-staining, and some of these arise from in situ nonspecific labeling with blood-borne radioactivity, rather than by transport to the terminals. We have shown that about 5 times more proteins are transported at fast than at intermediate transport rates. More than 50% of the fast proteins turn over rapidly and are gone in 24 h. Few intermediate proteins turn over rapidly. Since only 6% of the proteins in the relay nuclei (at 36 h) could not be detected in the optic tract at that time, transsynaptic labeling by breakdown and resynthesis must be small, if it occurs at all.

Animals↗

PRL and ACTH secretion following acute heat exposure, in intact and in hypothalamic deafferentated male rats.

Adult male rats, intact or bearing complete, anterior or posterior hypothalamic deafferentiations (CHD, AHD AND PHD, respectively) were acutely exposed to environmental temperature of 36 degrees C, and serum PRL and ACTH concentrations were determined by RIA. In intact animals, heat exposure resulted in elevated serum PRL and ACTH levels. None of the deafferentations affected basal serum PRL concentrations, whereas those of ACTH were elevated in both CHD and AHD, but not in PHD groups, as compared to intact controls. The PRL heat response was completely absent in CHD, attenuated in AHD, and delayed in PHD animals, and the ACTH heat response was absent in all three groups. These results demonstrate (1) that acute exposure to elevated environmental temperature stimulates secretion of PRL and of ACTH; (2) that this stimulation is carried out by diverse neural pathways; and, (3) that hypothalamic modulation of the secretion of PRL and ACTH is effected by independent mechanisms.

Adrenocorticotropic Hormone↗

Corticotrophin and corticosterone secretory patterns following acute neurogenic stress, in intact and in variously hypothalamic deafferented male rats.

Adult male rats, intact (N) or bearing complete (CHD), anterior (AHD), or posterior (PHD) hypothalamic deafferentations, were acutely exposed to either visual or audiogenic stimulation. At 2, 4, 10 or 30 min following the onset of stress exposure the animals were decapitated and trunk blood was collected for ACTH (RIA) and corticosterone (CS, CBG) determinations. Basal serum concentrations of both hormones were elevated in CHD and AHD, but not in PHD animals as compared to N animals. In N rats, exposure to both stresses resulted in elevated serum ACTH and CS concentrations, with the ACTH response to audiogenic but not visual stimulation being biphasic. In CHD animals, serum ACTH concentrations decreased, and those of CS were unchanged following stress exposure. While audiogenic stimulation caused elevation in serum levels of both hormones in AHD rats, the normal ACTH and CS response to visual stimulation were completely abolished by anterior hypothalamic deafferentation. In PHD animals, no ACTH response to either of the stress exposures was apparent; in spite of this, partial CS responses were elicited. These data thus describe the temporal aspects of the ACTH and CS secretory responses to different neurogenic stresses, and provide insight into the neural pathways mediating these responses.

Adrenocorticotropic Hormone↗