Oxytocin content of the cerebrospinal fluid of dogs and its relationship to pain induced by spinal cord compression.

OBJECTIVES: To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs. STUDY DESIGN: Prospective controlled study. ANIMAL POPULATION: A total of 15 purpose-bred beagles and 17 client-owned dogs. METHODS: CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay. RESULTS: Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 +/- 2.0 pg/mL and 3.61 +/- 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 +/- 0.86 pg/mL and 6.80 +/- 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls (P < .005 and P < .0001 respectively). CONCLUSIONS: Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs. CLINICAL RELEVANCE: In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.

Guanine nucleotides are present in human CSF.

Several studies have shown that experimentally added guanine nucleotides (GN) may extracellularly modulate the glutamatergic system. However, there is no previous report of the extracellular occurrence of GN in the CNS. This study used HPLC to investigate the presence of GN in cerebrospinal fluid (CSF) samples of 26 patients. We demonstrated the extracellular presence of GN in the CNS. In human CSF, GMP was detected in a remarkably high concentration (236.20 microM). This evidence stimulates further investigation of extracellular GN modulation of neurotransmission, physiological mechanisms of action(s), and therapeutic potential(s) in the CNS.

[Importance of the study of the cytology and proteins of the spinal fluid in lumbago]. / Intérêt de l'étude de la cytorachie et de la protéinorachie dans les lombalgies.

In the cerebrospinal fluid (C.S.F.) of hundred patients suffering from lumbago we have studied the existence of cytobiochemical and cytoradiological correlations in order to confirm the demonstration of cytologic and biochemical signs of organicisty or seriousness of this frequent pathology. We have realized cytorachia, that is to say differential cells counts and formulas on C.S.F. samples after cytocentrifugation and staining associated with biochemical determinations. Cytologically 96% of C.S.F. samples had normal count but 67% of them had a disturbed formula often associated with hyperproteinorachia. We have found lymphocytes and histiomonocytes the normal cells of C.S.F. but also neutrophilic, eosinophilic and basophilic polymorphonuclears and above all leptomeningeal cells. A disturbed cytorachia is often related with a pathological radiological picture (68% of cases). A cytologic anomaly with hyperproteinorachia in the same C.S.F. sample seems to be a sign of seriousness and to reveal a resistance to medical treatment. A technical presentation of cytorachia and an attempt of physiopathological explanation of observed cytologic abnormalities are proposed.

Evaluation of beta-endorphin/beta-lipotropin immunoreactivity content in the CSF of patients affected by deafferentation pain syndromes.

Beta-endorphin/beta-lipotropin immunoreactivity (BE/BLPH-IR) content was evaluated in the CSF of patients suffering by deafferentation pain syndromes. BE/BLPH-IR CSF concentrations of these patients were compared with those obtained in a group of patients affected by low back pain and in a control group without pain problems. No statistically significant variation in BE/BLPH-IR levels were found between controls and subjects with different types of chronic pain.

Cerebrospinal fluid concentrations of beta-endorphin in chronic low back pain patients. Influence of depression and treatment.

Cerebrospinal fluid (CSF) beta-endorphin concentrations were determined before and after treatment in 28 patients suffering chronic neuralgic low back pain/sciatica. Nine patients carried the additional diagnosis of major depressive disorder. Pain treatment was multimodal and resulted in variable pain reduction. CSF beta-endorphin concentrations spanned a wide range with no association to age, gender, pain ratings, depressive symptomatology, and drug intake. CSF beta-endorphin concentrations were not influenced by the presence of major depressive disorder and did not change with successful treatment of pain and resolution of depression.

Neuropeptide converting enzyme activities in CSF of low back pain patients.

The activity levels of a dynorphin converting enzyme (DCE), a substance P endopeptidase (SPE) and a substance P alpha-amidating enzyme (SP-GLYE) were measured in the cerebrospinal fluid (CSF) of 90 patients with chronic low back pain, sciatica and neurological signs of rhizopathy. The DCE activity was significantly higher in men than in women. Age was related to the DCE activity independent of sex, i.e., older patients had higher enzyme activity. The activities of two substance P converting enzymes were not related to sex or age. Self-reported pain experience and affective covariates (anxiety, depression, hostility, somatization) of pain, and myelography data were not found to be related to the enzyme activity levels once adjustment had been made for sex and age. The activity levels of the enzymes measured here had no predictive value for the long-term outcome of rehabilitation and therapy at the 5-year follow-up of the patients. The sex difference in DCE activity provides further evidence in favor of the role of gender in the psychoendocrine coping with pain distress.

Substance P-like immunoreactivity in human cerebrospinal fluid.

In a study to elucidate molecular mechanisms in pain, substance P-like immunoreactivity (SP-LI) was measured in lumbar CSF from 75 patients with lower back pain. Two samples--one before and one after lidocaine treatment--were obtained from each patient, and total SP-LI was measured in unfractionated (no HPLC) samples. SP-LI data were separated into three categories: placebo responders, pharmacological responders, and pharmacological non-responders. A significant difference was observed between the total SP-LI measurement of first and second samples of pharmacological non-responders. Distribution of SP-LI immunoreactive molecular species in two CSF patient samples (no ODS) was analyzed with a combination of reversed phase (RP) HPLC and RIA. Immunoreactivity in collected HPLC fractions was measured at calibrated retention times of synthetic SP-sulfoxide (SP-O), SP, and SP. Qualitative and quantitative differences in those HPLC-RIA metabolic profiles were observed within and between those two patients' samples. These data indicate that the type and amount of SP metabolism and SP precursor-processing differs in CSF between these two representative patients and within the short amount of time elapsed between acquiring these two samples.

Alterations in cerebrospinal fluid concentrations of somatostatin-like immunoreactivity in chronic pain patients.

Concentrations of somatostatin-like immunoreactivity in cerebrospinal fluid were significantly reduced in chronic pain patients compared to control patients without chronic pain. This difference was not influenced by demographic or clinical characteristics. Somatostatin has been shown to be a neurotransmitter in animal nociception; pharmacologic doses of this substance have moderated human pain. Our findings provide evidence that somatostatin may be involved in the pathogenesis of the chronic pain state.

Opioid receptoractivity in CSF from an atypical lower back pain patient.

One patient's lumbar CSF sample out of 54 studied for lower back pain had an atypical metabolic profile of opioid receptoractivity. To test our hypothesis that neuropeptides play a role in human lower back pain, endogenous opioid receptoractivity was compared between a control and that atypical sample. Two lumbar puncture samples were obtained from those two patients, one before and one after clinical evaluation. Total opioid receptoractivity was measured in each sample before HPLC separation, and opioid receptoractivity was measured in each fraction after HPLC separation. The latter data represent a metabolic profile of opioid receptoractivity in the human lumbar CSF. Those data demonstrate that the atypical patient had opioid receptoractivity measurements (total and profile) differing in a qualitative and quantitative sense from the other 53 patients studied. CSF opioid receptoractivity reflects the metabolism of opioid neuropeptidergic systems in the physiology in those patients, and opioid peptides may play a role in lower back pain.

CSF monoamine metabolites in chronic pain.

Metabolites of selected neurotransmitters (5-HIAA, HVA and DOPAC) and beta-endorphin were measured in the CSF of 39 chronic pain patients and compared to controls. Twelve of the pain patients also fulfilled criteria for major depression. The concentration of 5-HIAA was increased in female but not male pain patients; there was no significant difference in the CSF concentrations of HVA and DOPAC. The presence of depression did not influence the concentrations of neurotransmitters. No correlation was found between the concentrations of monoamine metabolites and beta-endorphin. However, there was a positive correlation between 5-HIAA and HVA in controls and chronic pain patients without depression but not in depressed patients. It is concluded: chronic pain states are associated with elevation of CSF 5-HIAA in female patients; depression abolishes a positive correlation between 5-HIAA and HVA.

HPLC receptorassay of opioid peptides in the cerebrospinal fluid of lower back pain patients.

Total opioid peptide receptoractivity in human cerebrospinal fluid is measured in patients who are experiencing lower back pain. Desalted CSF is eluted from a C18 Sep-Pak and is subjected to a radioreceptorassay (RRA) that employs tritiated etorphin, which is a ligand that is effectively displaced by opioids from several different types of opioid receptors. Three clinical groups have significantly different endogenous levels of 2.4, 4.5, and 6.4 pmol of methionine enkephalin-equivalents per mL CSF. Those three levels indicate that more opioid activity is correlated with the amount of drug to relieve the patient's perception of pain. When the total opioid content exceeds an empirical threshold, the sample is further fractionated with gradient reversed phase HPLC, and the opioid receptoractivity in each HPLC fraction is measured to determine the characteristic pattern of those receptoractive opioid peptides present in that patient's CSF. Different HPLC RRA patterns are found for different clinical categories. A possible interpretation of these two different sets of data.is that a lesion exists in one or several of the opioid peptidergic systems (metabolism, receptors) in this particular patient population.

Prolactin and cortisol responses to the experience of low back pain.

Demographic, clinical and psychological characteristics of 92 patients with low back pain were correlated with prolactin and cortisol levels in cerebrospinal fluid (CSF). Somatization and depression scores correlated statistically significantly with the CSF serum ratio of prolactin both in men and in the total group. An increased CSF/serum ratio of cortisol was slightly associated with somatization scores in the total group. Multiple stepwise regression, furthermore, revealed that somatization, anxiety and one of the pain indices contributed to the variance in the CSF prolactin level, which was mostly dependent on the respective serum level. Sex and electromyographic findings (EMG) accounted for 12 and 7%, respectively, of the variance in the afternoon cortisol levels. Women reported more somatization and depression feelings than did men. Most of the data support our earlier assumption that male and female pain patients have different coping mechanisms. In spite of the common underlying endocrine responses to distress in men and women, gender differences in psychological response appear to modify endocrine responses to the experience of low back pain.

Neurotransmission and the experience of low back pain; no association between CSF monoamine metabolites and pain.

We have investigated the possible associations between the demographic, clinical and psychological characteristics of 80 patients with low back pain and the CSF levels of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the principal central nervous system metabolites of serotonin, dopamine and noradrenaline, and of tryptophan, the amino acid precursor of serotonin. Neither the clinical measures nor the psychological characteristics were significantly correlated with the CSF neurochemistry. Therefore the hypothesis about an intimate relationship between monoaminergic neurotransmission and the experience of chronic low back pain was not confirmed. Among the other factors studied, body height contributed most to the variance in both 5-HIAA and HVA concentrations; the levels of MHPG increased with age.

Prolactin and cortisol in cerebrospinal fluid: sex-related associations with clinical and psychological characteristics of patients with low back pain.

Clinical and psychological characteristics of 33 patients with low back pain were correlated with prolactin and cortisol concentrations in cerebrospinal fluid (CSF). A significant sex difference was found in CSF prolactin levels: women secreted more prolactin into the CSF than did men. High CSF cortisol levels were associated with a rhizographically-demonstrable abnormality, suggesting a relationship between cortisol and an 'organic' origin of pain symptoms. Impairment-disability indices also were associated with CSF hormone levels. Moreover, the two hormones had dissociated psychological correlates. Prolactin was related to depression and anxiety, whereas cortisol was related to somatization. Sex differences were observed in the cortisol response to the symptoms of chronic low back pain, especially in the presence of anxiety and somatization. The sex differences in psychoneuroendocrine and emotional responses suggest that male and female pain patients have different coping mechanisms.

Relief of postlaminectomy syndrome in selected patients by injection of autogenous cerebrospinal fluid.

We have been using the differential spinal block to study patients referred to our Pain Clinic for treatment of their chronic pain syndromes. In a selected group of chronic-pain patients from whom cerebrospinal fluid (CSF) could not be obtained at the L4 or L5 interspace, administration of autogenous CSF obtained at a higher interspace gave immediate and complete but temporary pain relief. Endorphins were present in these autogenous CSF samples. These studies, indicating that CSF even from chronic-pain patients contains analgesic substances (possibly endorphins), may point to new treatment modalities for certain chronic back pain syndromes.

Diagnostic CSF analysis in neurological practice.

In order to establish the diagnostic value of clinical chemical analyses of C.S.F. samples, the C.S.F. data from seven hundred patients have been evaluated. The authors discuss the influence this investigation has exerted on their differential diagnostic evaluation.

Cerebrospinal fluid protein findings in various lower back pain syndromes.

Cerebrospinal fluid (CSF) total protein, albumin and IgG concentrations were measured in 53 patients with lower back pain syndromes. In the majority of the patients (81 %) the protein values were within normal ranges, a finding contrary to previous studies. In six of 28 patients with acute lumbar disc prolapse and in two of four cases with spinal stenosis, a clearly abnormal protein pattern was observed, while patients who had been earlier operated on for disc prolapse showed normal values. The calculated permeability indexes suggest that the elevation of various proteins is linked with increased permeability across the blood-brain barrier and that the local immunoglobulin synthesis in CNS is lacking. In only one of the cases with an abnormal CSF protein pattern could no evidence of the cause of the pathological finding be observed in subsequent examinations.