Clinical study of cerebrospinal fluid neuropeptides in patients with primary trigeminal neuralgia.

OBJECTIVES: To investigate the expression levels of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP), and ß-endorphin in the cerebrospinal fluid (CSF) and peripheral blood of patients with primary trigeminal neuralgia (TN). PATIENTS AND METHODS: We included 20 patients with primary TN who underwent percutaneous radiofrequency thermocoagulation and collected four types of samples from all of them: sample A: CSF samples; sample B: peripheral blood samples; sample C: peripheral blood samples collected one day before the operation; sample D: peripheral blood samples withdrawn one day after the operation. Another 20 CSF samples of patients with nervous system disease or gynecological disease were collected as a control (sample E). Samples A and B were obtained at the same time. We also evaluated the expression of CGRP, SP, ß-endorphin, and VIP by visual analog scale (VAS) scores one day before and one day after the operation. In addition, heart rate (HR) at baseline and at the time of sample collection, mean arterial pressure (MAP), and all side effects of the procedure were recorded. RESULTS: Significance were found concerning about CGRP, SP, ß-endorphin, and VIP in TN patients and the controls (P<0.001). The expression of CGRP, SP, and VIP in sample A was higher than that in sample E. However, the ß-endorphin level in sample A was lower than that in sample E. There was a positive correlation between sample A and B regarding the expression of CGRP, SP, ß-endorphin, and VIP (P<0. 01). There was no relationship between the time of disease onset and the expression of CGRP, SP, ß-endorphin, and VIP in sample A and sample B (P>0.05). No difference was detected between the neuropeptides levels in samples B and C (P>0.05). Notably, VAS in sample D was significantly lower than that in sample C (P<0.01). Finally, there was no difference between the intraoperative HR and MAP values in the studied samples. CONCLUSION: In primary TN patients, the blood levels of CGRP, SP, ß-endorphin, and VIP were associated with those in CSF samples. There was a significant difference between the levels of the four neuropeptides in CSF and control samples. Our results also indicated that the levels of neuropeptides in blood samples can be tested for those in CSF. The disease onset and duration exerted insignificant effects on the production and release of CGRP, SP, ß-endorphin, and VIP.

Do low levels of beta-endorphin in the cerebrospinal fluid indicate defective top-down inhibition in patients with chronic neuropathic pain? A cross-sectional, comparative study.

OBJECTIVE: Pain medicine still lacks mechanism-specific biomarkers to guide diagnosis and treatment, and defective top-down modulation is an important factor in the pathophysiology of chronic pain conditions. Using modern analytical tools and advanced multivariate statistical analysis, the aim of this study was to revisit two classical potential biomarkers of pro- and anti-nociception in humans (substance P and beta-endorphin), focusing particularly on the cerebrospinal fluid (CSF). DESIGN: Cross-sectional, comparative, observational study. SUBJECTS: Patients with chronic, post-traumatic and/or post-surgical, neuropathic pain refractory to conventional treatment (N = 15) and healthy controls (N = 19) were included. METHODS: Samples were taken from CSF and blood, and levels of substance P and beta-endorphin were investigated using a Luminex technology kit. RESULTS: We found low levels of beta-endorphin in the CSF of neuropathic pain patients (66 ± 11 pcg/mL) compared with healthy controls (115 ± 14 pcg/mL) (P = 0.017). Substance P levels in the CSF did not differ (20 ± 2 pcg/mL, 26 ± 2, P = 0.08). However, our multivariate data analysis showed that belonging to the patient group was associated with low levels of both substances in the CSF. A higher correlation between the levels of beta-endorphin and substance P in CSF was found in healthy controls than in patients (rs = 0.725, P < 0.001 vs. rs = 0.574, P = 0.032). CONCLUSIONS: Patients with chronic neuropathic pain due to trauma or surgery had low levels of beta-endorphin in the CSF. We speculate that this could indicate a defective top-down modulation of pain in chronic neuropathic pain. Our results also illustrate the importance of taking a system-wide, multivariate approach when searching for biomarkers.

A potential role for substance P and interleukin-6 in the cerebrospinal fluid of Cavalier King Charles Spaniels with neuropathic pain.

BACKGROUND: Neuropathic pain can be a clinical sign in Cavalier King Charles Spaniels (CKCS) with syringomyelia. The pathophysiology of this pain is not fully understood. HYPOTHESIS: Neuropathic pain in CKCS is a result of a neuroinflammatory process. ANIMALS: Twenty-six client-owned dogs: 15 dogs with clinical signs of cervical hyperesthesia (group 1), and 11 dogs without of clinical signs (group 2). METHODS: Dogs were examined by magnetic resonance imaging (MRI). Interleukin-6, tumor necrosis factor alpha, and substance P were measured in CSF and compared with morphological findings on MRI and clinical pain scores. RESULTS: All dogs without clinical signs had symmetrical syringomyelia, whereas in the group with pain, 6 dogs had symmetrical and 9 dogs had asymmetrical syringomyelia. Pain and syringomyelia asymmetry were correlated, and a strong association between pain and dorsal horn involvement of syringomyelia was observed. There was no significant difference between the mean width of the syringomyelia in dogs with or without pain. The concentrations of interleukin-6 and substance P were significantly higher in dogs with neuropathic pain. Tumor necrosis factor alpha was not detected in either group. Concentrations of substance P were significantly higher in dogs with asymmetrical syringomyelia or dorsal horn involvement, whereas interleukin-6 concentrations were not significantly different between groups. CONCLUSION: Release of interleukin-6 and substance P may initiate proinflammatory effects leading to development of persistent pain in CKCSs with syringomyelia.

Cerebrospinal fluid neurotransmitter changes during the perioperative period in patients undergoing total knee replacement: a randomized trial.

BACKGROUND: Total knee replacement (TKR) is of enormous benefit to patients with osteoarthritis of the knee; however, the acute postoperative pain can be severe and difficult to manage. The role of major spinal cord neurotransmitters in this acute postoperative period is not clear, although there are a few studies in humans. We performed the first prospective clinical study undertaken to delineate the changes in the spinal neurotransmitters after a surgery such as TKR. Furthermore, we also determined whether antihyperalgesic drugs at clinically acceptable doses modulate spinal neurotransmitter concentrations in patients during the perioperative period. METHODS: All patients had a spinal needle placed in the lumbar region and cerebrospinal fluid (CSF) obtained for baseline measurement of the neurotransmitters. An intrathecal catheter was then placed for spinal anesthesia for standard TKR and for continuous spinal postoperative analgesia. The spinal catheter was also used postoperatively to sample CSF at 2, 4, 8, 12, 24, and 32 hours after catheter placement. CSF samples were assayed for norepinephrine, substance P, calcitonin gene-related peptide (CGRP), and glutamate concentrations. SF-36 (36-item Short Form Health Survey) was measured preoperatively. Numerical rating scale (NRS) pain scores and intrathecal analgesic consumption were recorded postsurgery at 4-hour intervals for 32 hours. We performed a randomized, placebo-controlled, double-blind trial with 3 drug groups (n = 16 per group): placebo; single-dose pregabalin (150 mg administered before surgery); and multidose pregabalin (150 mg administered presurgery and 12 and 24 hours later), to determine the effect of an antihyperalgesic drug such as pregabalin on spinal neurotransmitters. RESULTS: Forty-eight patients were randomly assigned to the 3 perioperative treatment groups, and multiple CSF samples were successfully obtained from 44 patients. Before surgery, increased bodily pain (from preoperative SF-36 measure) was correlated with increased CSF norepinephrine concentration (P = 0.044). Compared with presurgery values, norepinephrine levels were lower in the placebo group at the 2- and 4-hour time points (P < 0.005) whereas in the single and multidose groups, the reduction (P < 0.001) continued until 12 and 24 hours, respectively. Substance P CSF levels had an early peak value (at 2 hours) in all 3 groups, and then returned to baseline. Compared with baseline value, the CGRP CSF levels only decreased at the 32-hour time point in the placebo group, but in both pregabalin groups, CGRP levels decreased over the 4- to 32-hour period. In the placebo group only, CSF glutamate decreased over 4 to 32 hours compared with presurgery values. However, there was no difference in the CSF neurotransmitter concentrations among the 3 treatment groups over the 32-hour sampling period. In the placebo group, the early NRS pain score area under the curve, AUC [0-12 hours], was positively correlated (R = 0.67, P = 0.0088) with the CSF norepinephrine concentration AUC [12-24 hours], but none of the other neurotransmitters was correlated with the NRS. None of the CSF neurotransmitter concentrations correlated with postoperative analgesic consumption. CONCLUSION: In the perioperative period, the concentration changes of the 4 spinal neurotransmitters have a distinct time course. CSF substance P seems to increase very rapidly with surgical intervention, whereas the CSF norepinephrine concentration tends to decrease. At clinical doses, pregabalin does not seem to modulate these spinal neurotransmitter concentrations.

Pemirolast reduces cisplatin-induced kaolin intake in rats.

Emesis is the most feared side effect in patients who are undergoing cancer chemotherapy. In particular, cisplatin causes severe acute and delayed emesis. Although early vomiting is well controlled by 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonists, delayed-phase vomiting is not sufficiently controlled. Substance P is thought to be involved in the development of emesis, and tachykinin NK(1) receptor antagonists can inhibit delayed vomiting. We previously have reported that substance P is involved in the paclitaxel-induced hypersensitivity reaction in rats, and anti-allergic agent pemirolast reduces these reactions via inhibition of substance P release. In the present study, we investigated the effect of pemirolast on cisplatin-induced kaolin intake, which is an index of nausea/vomiting in the rat. Cisplatin (5 mg/kg, i.p.) induced kaolin intake and reduced normal feed intake from days 1 to 5 after injection. Cisplatin-induced kaolin intake was significantly reduced by co-administration of ondansetron (2 mg/kg, i.p.), a 5-HT(3) receptor antagonist, and dexamethasone (2 mg/kg, i.p.) from days 1 to 5. Similarly, pemirolast (10 mg/kg, p.o.) and the tachykinin NK(1) receptor antagonist aprepitant (10 and 30 mg/kg, p.o.) significantly reduced cisplatin-induced kaolin intake on days 3 and 4. Moreover, pemirolast at the same dose significantly reversed the cisplatin-induced increase in the cerebrospinal fluid level of substance P in rats. These results suggest that substance P is involved in cisplatin-induced kaolin intake in rats, and pemirolast reduces kaolin intake by inhibition of substance P release.

Corticotropin-releasing factor, interleukin-6, brain-derived neurotrophic factor, insulin-like growth factor-1, and substance P in the cerebrospinal fluid of civilians with posttraumatic stress disorder before and after treatment with paroxetine.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with altered concentrations of stress-related neurohormones, neurotrophins, and neuropeptides in plasma and serum; however, few studies have examined central alterations of these measures in individuals with PTSD. Furthermore, no study to date has evaluated the effects of successful antidepressant treatment on cerebrospinal fluid (CSF) abnormalities in PTSD. METHOD: Sixteen medication-free outpatients with chronic PTSD (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria) due to physical and/or sexual abuse or motor vehicle accidents (mean ± SD age = 36 ± 11.4 years, 12 women) and 11 nontraumatized healthy subjects (mean ± SD age = 35.3 ± 13.1 years, 7 women) underwent a lumbar puncture for collection of CSF. Seven PTSD patients had a repeat lumbar puncture 12 weeks later, after successful treatment of PTSD with paroxetine. CSF was analyzed for corticotropin-releasing factor (CRF), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), and substance P concentrations. The study was conducted between January 2003 and August 2004. RESULTS: Compared to nontraumatized healthy controls, patients with chronic PTSD had similar pretreatment concentrations of CSF CRF, IL-6, BDNF, IGF-1, and substance P. Posttreatment CSF measures did not change significantly in patients whose symptoms remitted with paroxetine. CONCLUSIONS: Chronic, moderate PTSD due to civilian trauma, without psychotic symptoms and without significant rates of comorbid depression, alcohol dependence, or substance dependence, is not associated with abnormalities in CSF CRF, IL-6, BDNF, IGF-1, or substance P levels. Despite substantial reduction in PTSD symptoms, antidepressant treatment does not alter normal central concentrations of these neurochemicals, with the possible exception of substance P.

Propofol/alfentanil and propofol/ketamine procedural sedation in children with acute lymphoblastic leukaemia: safety, efficacy and their correlation with pain neuromediator expression.

Invasive procedures, such as the lumbar puncture, can cause anxiety and pain in children undergoing treatment for acute lymphoblastic leukaemia (ALL). We investigated the safety and efficacy of two different protocols for analgo-sedation in 20 children with ALL undergoing lumbar puncture. We have conducted a prospective, cross-over study. Protocol A was composed of an association between propofol and alfentanil. Protocol B consisted in the combination of propofol and ketamine. We also evaluated the levels of nerve growth factor, substance P and enkephalins in the cerebrospinal fluid of these patients. All patients showed a satisfactory sedation and analgesia. We found a statistically significant difference of vital parameters between protocol A and protocol B, while there were no significant differences between sedation scores and the other parameters evaluated. Patients in protocol A showed a higher incidence of major side effects, such as respiratory depression. Pain neuromediator levels did not show any statistical difference between the two groups. This study shows that both protocols are effective to obtain a good sedation and analgesia in children with ALL undergoing lumbar puncture, but the association between propofol and ketamine appears to be safer due to the lower incidence of side effects.

Fibromyalgia: an update and immunological aspects.

Fibromyalgia syndrome (FMS) is now understood as a chronic pain syndrome, and recent evidence indicates it is not a pure psychosomatic disorder. We review the current knowledge in FMS pain pathways, focusing on the central system sensitization phenomenon and the abnormalities in the inhibitory pain systems. Chronic headache is one of the most common symptoms in FMS, and better knowledge of their common pathophysiologic features can help us understand both conditions better. These features include the nerve growth factor actions and failure of the endocannabinoid system. In addition, we review new immunological aspects of FMS, both in their humoral (autoantibodies, antipolymer antibodies) and cytokine (interleukin-2) aspects.

Fibromyalgia--management of a misunderstood disorder.

PURPOSE: The purpose of this article is to review (a) what is currently known about the pathophysiology of fibromyalgia (FM), (b) how to identify patients who are susceptible to this disorder, and (c) the recommended pharmacological and nonpharmacological treatment options. DATA SOURCES: Data sources include reviews and original research from scholarly journals and Internet sites. CONCLUSIONS: There are approximately 6 million individuals in the United States diagnosed with FM, making it the third most prevalent rheumatologic disorder in this country. Failure to identify a specific causal mechanism for FM has resulted in a shift in the focus of research from etiology to treatment (Baumstark & Buckelew, 2002). Based on the literature, the most successful interventions for reduction of chronic symptoms in the FM patient is a combination of education, psychological assistance, and exercise, along with medications. It is essential that nurse practitioners (NPs) understand the issues and concerns of patients afflicted with this complex disorder. Although the organic etiology of FM syndrome remains unclear, the goals of treatment are to control pain and improve adjustment, well-being, and daily functioning of these patients to the maximum extent possible. IMPLICATIONS FOR PRACTICE: NPs are in a unique position to help identify patients who may be suffering from FM or those diagnosed with FM reporting inadequate relief of symptoms. The incomplete understanding of the biological underpinnings, as well as the multiple symptoms that characterize FM syndrome, make it a challenging disorder to diagnose and treat. It takes time and patience to care for FM patients, and there are no "quick fixes." Diagnosis is made by a combination of patient history, physical examination, laboratory evaluations, and exclusion of other causes of symptoms confused with FM. Understanding the symptomology and recommended treatments will allow NPs to give appropriate care that may include making referrals for multidisciplinary treatment of these complex patients.

Clinical significance of neurobiochemical profiles in the lumbar cerebrospinal fluid of Alzheimer's disease patients.

Immunoreactivities of total apolipoprotein E (ApoE-IR), amyloid beta peptide(1-42) (Abeta42-IR), interleukin-6 (IL-6-IR), substance P (SPIR) and total tau protein (TTIR) were measured in lumbar cerebrospinal fluid samples of patients with Alzheimer's disease (AD), non-Alzheimer's dementias (NAD), neurological disorders without cognitive impairment (OND) and controls without central nervous system disease using sensitive and specific enzyme immunoassay methods. TTIR was highly significantly increased (P < 0,001) and Abeta42-IR was significantly decreased (P < 0,001 vs. OND/CO, P < 0,03 vs. NAD) in the AD cohort compared with the other diagnostic groups. Significant increases in AD were also found for ApoE-IR (P < 0,001) and IL-6 (P < 0,03), but there was a considerable overlap between groups. In the total AD cohort, SPIR was not significantly changed, but AD patients with late disease onset (>65 years) showed significantly higher values than both early onset patients (<65 years) and controls (P < 0,05). Discriminant function analysis showed that Abeta42-IR (cut-off value 375pg/ml) and TTIR (cut-off value 440 pg/ml) levels contributed most to the group classification of patients. At 85% sensitivity for AD and 100% specificity for controls, the combined evaluation of Abeta42-IR and TTIR in this cross-sectional study resulted in a graph separating AD from non-AD patients with increased specificity of 91% and 75% for AD versus OND and NAD, respectively.

A high-recovery extraction procedure for quantitative analysis of substance P and opioid peptides in human cerebrospinal fluid.

This study reports an improved approach for the determination of neuropeptide levels in human cerebrospinal fluid (CSF). The method is based on sample acidification followed by liquid-liquid extraction (LLE) combined with radioimmunoassay. It was applied to study the recovery and level of some opioid peptides (Met-enkephalin-Arg(6)-Phe(7) and Leu-enkephalin-Arg(6)), substance P and the substance P(1-7) fragment, which are all compounds known to be present in human CSF. The results indicated that the use of LLE highly improved the recovery of these peptides compared to current liquid-solid-phase extraction methods by using silica gel cartridges or mini-columns for ion-exchange chromatography. Peptides added to CSF in concentrations down to 10 fmol/ml were recovered in yields exceeding 80%. The mean recovery of synthetic peptides as recorded by radioimmunoassay in the LLE procedure was significantly improved when HCl was added to the sample. In contrast, when the (125)I-labeled analogues of the peptides were added to CSF samples, the mean recovery of the four labeled peptides using the LLE procedure was markedly reduced in acidified samples. We also found that the inclusion of HCl effectively improved the removal of proteins present in the samples. As an application the levels of substance P and Met-enkephalin-Arg(6)-Phe(7) in CSF samples from patients with chronic pain (fibromyalgia syndrome) were measured using the new procedure. It was possible to confirm a significant difference in the CSF levels of both peptides when comparing patients and controls.

Chronic fatigue syndrome differs from fibromyalgia. No evidence for elevated substance P levels in cerebrospinal fluid of patients with chronic fatigue syndrome.

Levels of substance P were determined in the cerebrospinal fluid (CSF) in 15 patients with chronic fatigue syndrome (CFS). All values were within normal range. This is in contrast to fibromyalgia (FM). The majority of patients with FM have increased substance P values in the CSF. The results support the notion that FM and CFS are different disorders in spite of overlapping symptomatology.

Advances in fibromyalgia: possible role for central neurochemicals.

The neurophysiologic term allodynia has been applied to fibromyalgia because people with that disorder experience pain from pressure stimuli which are not normally painful. The nociceptive neurotransmitters of animal studies are now relevant to this human model of chronic, widespread pain. Evidence is presented to implicate several chemical pain mediators (including serotonin, substance P, nerve growth factor, and dynorphin A) in the pathogenesis of fibromyalgia. This perception is hopeful because it offers many new options for the development of innovative therapy.

Intrathecal adenosine analog administration reduces substance P in cerebrospinal fluid along with behavioral effects that suggest antinociception in rats.

UNLABELLED: Adenosine and adenosine analogs induce analgesia in humans and presumed antinociception in animal models when administered both systemically and intrathecally. In the present investigation in rats, we studied the effects of intrathecally administered adenosine analogs, with or without systemic coadministration of an adenosine antagonist (theophylline), on substance P (SP) and calcitonin gene-related peptide (CGRP) concentrations in cerebrospinal fluid (CSF). In parallel, nociceptive reflex testing (tail immersion latency) and motor function were evaluated. The potent unselective adenosine receptor agonist N-ethylcarboxamide-adenosine (NECA) and the relatively adenosine A1 receptor selective agonist R-phenyl-isopropyl-adenosine (R-PIA) both reduced SP-like immunoreactivity (-LI) by 50%, whereas CGRP-LI remained unchanged. There was a dose-dependent increase in tail immersion latency. This effect was present without motor impairment when R-PIA was administered in doses up to 5 nmol. R-PIA (10-100 nmol), as well as 1-100 nmol of the unselective agonist NECA, produced dose-dependent motor impairment. The reduction of SP-LI as well as the behavioral effects were reversed by theophylline. We conclude that SP reduction in CSF, which possibly reflects reduced SP turnover after adenosine receptor stimulation, provides an additional possible mechanism of action for the analgesic effects of adenosine. IMPLICATIONS: We studied the interactions between the known pain mediator substance P and substances with effects similar to the endogenous pain modulator adenosine in rats. The results suggest that the pain-reducing effect of adenosine is, at least partly, due to a reduction of substance P in cerebrospinal fluid.

Alterations in perivascular dilatory neuropeptides (CGRP, SP, VIP) in the external jugular vein and in the cerebrospinal fluid following subarachnoid haemorrhage in man.

A possible involvement of perivascular vasodilatory neuropeptides in subarachnoid haemorrhage (SAH) has been evaluated in man by measuring the levels of calcitonin gene related peptide (CGRP)-, substance P (SP)- and vasoactive intestinal peptide (VIP)-like immunoreactivity (LI) in the cranial venous outflow and in CSF in 34 patients admitted to the hospital after an acute SAH. After operation with aneurysm clipping and nimodipine treatment, blood samples were taken from the external jugular vein (EJV) or cerebrospinal fluid (CSF) and analysed for neuropeptide levels with specific radioimmuno assays (RIA) during the postoperative course. The degree of vasoconstriction in the patients was monitored with Doppler ultrasound recordings bilaterally from the middle cerebral (MCA) and internal carotid arteries (ICA) following the EJV blood sampling every second day. The mean value of all CGRP-LI measurements in EJV during the entire course of SAH (n = 20) revealed a significantly higher level as compared to controls. The highest CGRP-LI levels were found in patients with the highest velocity index values (vasospasm). The relationship Vmean MCA/Vmean ICA was used as an index of vasoconstriction. In patients with MCA aneurysms (n = 10), a significant correlation (r = 0.65, p < 0.05) was found between the vasospasm index and CGRP-LI levels. There were no changes observed in the SP- and VIP-LI levels. Alterations in cerebrovascular tone induced by changing arterial CO2 tension or lowering of blood pressure (ketanserin infusion test) did not alter the levels of the perivascular peptides in the EJV. In addition, CGRP-, SP-, VIP- and neuropeptide Y (NPY)-LI were analysed in CSF in the post-operative course after subarachnoid haemorrhage (SAH) in 14 patients. The CSF VIP-LI was lower in SAH than in control (p < 0.05). The CGRP-LI level was measurable in SAH CSF but not in CSF of controls. In individual patients with marked vasoconstriction increased levels of CGRP-LI (up to 14 pmol/L) and NPY-LI (up to 232 pmol/L) were observed. The results of this study are in support of our hypothesis that there is an involvement of the sensory peptide CGRP in a dynamic reflex aimed at counterbalancing vasoconstriction in SAH.

Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome.

OBJECTIVE: To measure, and seek clinical correlates with, levels of substance P (SP) in the cerebrospinal fluid (CSF) of fibromyalgia syndrome (FMS) patients. METHODS: CSF from 32 FMS patients and 30 normal control subjects was tested for SP by radioimmunoassay. Clinical measures included tender point examination and standardized questionnaires. RESULTS: CSF SP levels were 3-fold higher in FMS patients than in normal controls (P < 0.001), but they correlated only weakly with tenderness found on examination. CONCLUSION: SP is significantly elevated in FMS CSF, but other abnormalities must exist in FMS to more fully explain the symptoms.

Effects of dorsal root entry zone lesions on CSF and plasma neuropeptides and catecholamines.

Effects of dorsal root entry zone lesions (DREZLs) on cerebrospinal fluid (CSF) and plasma concentrations of neuropeptides, catecholamines, and cyclic nucleotides were studied in 9 patients with intractable chronic pain. Contents of beta-endorphin-like-material in CSF decreased in all patients 12-17 days following DREZLs during which complete to good pain relief was achieved. Contents of beta-endorphin-like-material in CSF increased again about one month after DREZLs in two and remained unchanged in one of three patients tested, who complained of partial reappearance of pain. Contents of beta-endorphin-like-materials in plasma showed no significant changes after DREZLs. Substance P, noradrenaline, adrenaline, and cyclic nucleotide levels in both CSF and plasma were variable among the subjects and did not change significantly following the operations. Thus, the results suggest that production of beta-endorphin-like-material in the central nervous system is decreased by DREZL, though the increase in its turn-over might not be neglected. The mechanisms of the decrease in contents of beta-endorphin-like-material in CSF after DREZLs were discussed in terms of our current knowledge of pain and pain inhibitory systems.

Somatostatin, substance P, prolactin and vasoactive intestinal peptide levels in serum and cerebrospinal fluid of children with seizure disorders.

Seventy patients aged from one month to 18 years with seizure disorders were classified into three groups: I. Patients who had hard control seizure attacks even under medication; II. those who had occasional seizure attacks (less than 6 times per year) and III. those who had no seizure attacks after receiving medication for at least one year. Blood samples were taken for somatostatin, substance P, prolactin and vasoactive intestinal peptide (VIP) assays. Lumbar puncture was made in 32 children and CSF samples were also assayed for neuropeptides. Somatostatin levels in serum were significantly elevated in group I and group II (P = 0.05, ANOVA) but not in group III and control group. Similar observations were made in substance P, prolactin and VIP studies. In CSF, the somatostation can better indicate the difference between epileptic and normal children (comparison with group I, P greater than 0.001; with group II, P less than 0.001; even with those who were seizure free after medication, P less than 0.05). In conclusion, the levels of several neuropeptides (somatostatin, substance P. prolactin, VIP) were elevated in children with seizure disorders both in serum and CSF. The present investigation provides a new category for the understanding of the pathogenesis, treatment as well as prognosis of seizure disorders.