Body mass index, sexual difficulties and sexual satisfaction among people in regular heterosexual relationships: a population-based study.

BACKGROUND/AIMS: The aims of this study were to clarify the relationship between body mass index (BMI) and sexual difficulties and to investigate if BMI influenced sexual satisfaction, over and above the effects of sexual difficulties. METHODS: Cross-sectional analyses of a nationally representative computer-assisted telephone interview. Eight thousand, six hundred and fifty-six respondents were recruited by random digit dialling in 2004-2005. Only those in a sexually active, heterosexual relationship were included in the current analyses. RESULTS: After adjustments for demographic factors, both overweight and obese male and female participants were more likely to report worrying during sex about whether their body was unattractive. Among women, associations were also found between higher BMI and lack of interest in sex. No other significant associations between BMI and sexual difficulties were evident. There was an association between BMI and extreme physical pleasure for women but not men over and above the effects of sexual difficulties, with obese women being more likely than normal weight women to report extreme physical pleasure. No associations were found for either men or women between BMI and whether or not they reported extreme emotional or sexual satisfaction with their relationship. CONCLUSIONS: With the exception of body image difficulties, there is little association between BMI and self-reported sexual difficulties. Furthermore, extreme sexual and emotional satisfaction appeared to be associated with the presence or absence of sexual difficulties and not overly influenced by BMI. Overall, clinicians and patients should be aware that being overweight is not necessarily detrimental to sexual functioning.

Association of lipoprotein(a) with puberty in IDDM.

OBJECTIVE: To determine serum lipoprotein(a) in a large sample of IDDM and control children and to examine a possible association with puberty. RESEARCH DESIGN AND METHODS: Serum lipoprotein(a), apoB-100, and apoA-I were measured under identical conditions in 170 Caucasian children with IDDM aged 12.3 +/- 3.59 yr and 233 Caucasian control children aged 13.6 +/- 1.12 yr. Patients with persistent microalbuminuria were excluded. Lipoprotein(a), apoB-100, and apoA-I were measured by nephelometry using a specific monoclonal antibody. Pubertal assessment was performed using Tanner staging and testicular volume measurement. RESULTS: Lipoprotein(a) was higher in the IDDM than control group (geometric mean 237 mg/L, 25-75th percentile 134-465 vs. 172 [99-316] mg/L, P = 0.0008). When analyzed according to pubertal stage, only pubertal and postpubertal patients had higher levels than control subjects (265 [148-560] vs. 174 [101-320] mg/L, P = 0.0001), with prepubertal patients showing no difference. Pubertal and postpubertal patients showed both higher lipoprotein(a) (P = 0.01) levels and higher albumin excretion rates (P = 0.02) than prepubertal patients, correcting for the other variable. Lipoprotein(a) was not related to HbA1c, albumin excretion rate, duration, age, sex, mean arterial pressure, or a family history of premature coronary artery disease in the IDDM group. Lipoprotein(a) was not higher in patients with overnight albumin excretion rate above the 95th percentile but below the microalbuminuric range. ApoB-100 did not differ between IDDM and control children. ApoA-I was significantly lower in the IDDM group (1.04 [0.94-1.17] vs. 1.21 [1.10-1.31] g/L; P < 0.0001). CONCLUSIONS: Pubertal and postpubertal IDDM patients have higher serum lipoprotein(a) than Caucasian control subjects. Our findings suggest a rise in lipoprotein(a) may occur during puberty in IDDM. Longitudinal studies are required to clarify the relationship between lipoprotein(a), albumin excretion rate, and puberty.

The effect of warfarin therapy on the charge properties of urinary prothrombin fragment 1 and crystallization of calcium oxalate in undiluted human urine.

Urinary prothrombin fragment 1 (UPTF1) is the principal protein in calcium oxalate (CaOx) crystals precipitated from human urine and is a potent inhibitor of CaOx crystallization, a property that should depend, at least in part, upon the extent of gamma-carboxylation of the 10 glutamic residues in its N-terminal region. Warfarin therapy limits full gamma-carboxylation of vitamin K-dependent proteins, including UPTF1. The aims of this study were to determine the effect of warfarin therapy on UPTF1, its occlusion into CaOx urinary crystals, and its influence on the crystallization of CaOx in undiluted human urine. In the first part of the study, urines were collected from six men prior to cardiac surgery and after stabilization on long-term warfarin treatment. Proteins in the urines and in the matrix of CaOx crystals precipitated from them were analyzed by two-dimensional SDS-PAGE and Western blotting. In urine, at least two charge variants of UPTF1 with low isoelectric point (pI) values were detected before and during warfarin therapy, but additional higher pI forms of the protein were also seen during anticoagulation. Nonetheless, the majority of UPTF1 was present in the more fully gamma-carboxylated state. CaOx crystals precipitated from the same urine samples contained only low pI forms of UPTF1. The effect of warfarin treatment on CaOx crystallization in urine was tested by collecting two consecutive 24-h urine samples from 16 men prior to cardiac surgery and during subsequent warfarin treatment. CaOx crystallization was induced in each sample by the addition of sodium oxalate. The size and volume of the particles deposited were determined using a Coulter counter, and the crystals were examined by scanning electron microscopy (SEM). There were no significant differences between the urinary metastable limits before or during warfarin treatment or in the total volume of crystals precipitated. A slight increase in the mean diameter of the crystalline particles precipitated from the urines during anticoagulant therapy was not significant. SEM showed little evidence of changes in overall particle size, although individual crystals of CaOx tended to be larger during warfarin treatment. It was concluded from these studies that the binding of UPTF1 to CaOx crystal surfaces is related to the degree of gamma-carboxylation of its Gla domain, which would also influence the protein's inhibitory effects on CaOx crystallization. However, during warfarin therapy the majority of UPTF1 exists in a highly charged state, indicating that it is completely, or almost completely, gamma-carboxylated, which would explain the lack of any difference between CaOx crystallization parameters in the urine of subjects before and during warfarin administration. We conclude that physiologically significant reductions in the inhibitory potency of UPTF1 would be likely to occur only as a result of proscription of gamma-carboxylation more extensive than that induced by warfarin.

Substituted vitamin K epoxide analogues. New competitive inhibitors and substrates of vitamin K1 epoxide reductase.

2- and 3-substituted vitamin K 2,3-epoxide analogues were synthesized and tested as inactivators, inhibitors, and substrates for beef liver microsomal vitamin K1 epoxide reductase. 2-(X)-3-phytyl-1,4-naphthoquinone 2,3-epoxides, where X is hydroxymethyl, chloromethyl, fluoromethyl, difluoromethyl, and formyl were all competitive inhibitors, but none was an inactivator. Only the 2-hydroxymethyl analogue was reduced to a quinone that was stable enough under the conditions of the experiment to be detected. Vitamin K1 epoxide analogues with modified phytyl chains (1'-hydroxy, 3'-fluoro with isomerized double bond, 1'-hydroxy and 1'-fluoro with saturated double bond, and the corresponding unsubstituted chains) were synthesized. All of the analogues were competitive inhibitors of vitamin K1 epoxide reductase. The nonfluorinated analogues also were shown to be substrates, being reduced to the corresponding quinone without enzyme inactivation. At least one other enzyme besides vitamin K1 epoxide reductase in beef liver microsomes also metabolizes all of these analogues.

An excitatory action of iontophoretically administered lithium on mammalian central neurones.

1 The action of iontophoretically administered lithium was studied on spinal Renshaw cells an interneurones and on supraspinal neurones in cerebral cortex, thalamus, hypothalamus and brain stem in anaesthetized cats and rats. 2 There was a correlation between the effects of Li+ and those of acetylcholine (ACh), although rather more cells were unaffected by Li+ than by ACh. 3 The usual effect was an excitation of rather slow onset, but occasionally effects were produced with time courses similar to those of ACh. The excitation was blocked by ACh antagonists and was best demonstrated with dihydro-beta-erythroidine on Renshaw cells. 4 The postsynaptic excitant action of ACh on Renshaw cells was reduced by Li+. 5 Depressant actions of Li+ were encountered on cells also depressed by ACh. 6 It is concluded that Li+ may facilitate cholinergic transmission at some sites in the CNS by increasing the release of ACh by an unknown mechanism. Similar effects at non-cholinergic synapses might also occur but would appear to be of less importance. Since facilitation of neuronal firing with Li+ was usually observed, the depressant effects on postsynaptic responses to ACh may be of little consequence.

The antinociceptive action of etorphine in the dorsal horn is due to a direct spinal action and not to activation of descending inhibition.

1--Etorphine, microinjected into the brainstem or administered intravenously, inhibited the firing of dorsal horn neurones to noxious heat in spinal or non-spinal anaesthetized cats and in decerebrate, non-anaesthetized cats with intact spinal cords. 2--Small doses of etorphine sometimes caused facilitation, especially when the cord was intact, but this was invariably followed by inhibition at higher doses. 3--The ED50 for inhibition (mean 3.9 micrograms/kg) after microinjection into nucleus raphe magnus, nucleus reticularis magnocellularis or the lateral tegmental field was similar at all sites in anaesthetized, non-spinal cats. 4--The ED50 for microinjection was not increased by spinal transection in anaesthetized cats (mean ED50, 2.6 micrograms/kg) and was similar to the ED50 in decerebrate, non-anaesthetized cats. 5--Intravenous administration was 2 to 3 times more effective than microinjection and the time course of inhibition was faster after intravenous administration than after microinjection. 6--It is concluded that etorphine inhibits dorsal horn neurones after microinjection or intravenous administration by a direct action on the spinal cord and not by activating a descending inhibition. After microinjection it rapidly enters the general circulation and subsequently distributes into the spinal cord. 7--It is also concluded that naloxone readily gains entry to the circulation from the brain because microinjection antagonized the effects of systemic etorphine on dorsal horn neurones in spinal cats.

A re-evaluation of acetylcholine receptors on feline Renshaw cells.

1 The effects of atropine, methylatropine and lachesine administered by ionophoresis were examined on responses of Renshaw cells to acetylcholine, acetyl-beta-methylcholine, nicotine and DL-muscarine in cats anaesthetized with pentobarbitone or chloralose. 2 The antagonists were as effective in antagonizing excitation by nicotine as they were in antagonizing excitation by acetylcholine and were only slightly more effective in antagonizing excitation by acetyl-beta-methylcholine. 3 These results are discussed in relation to the characterization of acetylcholine receptors on Renshaw cells. 4 It is concluded that there are two distinct populations of receptors but that the nicotinic receptors are non-selective in their activation by agonists and antagonists, whereas the muscarinic receptors display greater selectivity.

Inhibition by substance P of some peripheral actions of acetylcholine in the cat.

1 The effect of substance P on contractions of the nictitating membrane and pressor responses to acetylcholine (ACh) and dimethylphenyl-piperazinium (DMPP) which were mediated via nocotinic receptors was studied in cats anaesthetized with chloralose.2 Substance P (2-20 nmol) injected into the lingual artery giving estimated concentrations in arterial blood of 10(-6) to 10(-5) M, or intravenously giving estimated concentrations in blood of 10(-8) to 10(-7) M, reduced hexamethonium-sensitive but not atropine-sensitive responses.3 The pressor effects of ACh and DMPP injected intra-arterially in atropinized and non-atropinized cats respectively were consistently attenuated by substance P given intra-arterially or intravenously.4 The contractile effect of ACh in atropinized and of DMPP in non-atropinized cats was attenuated by substance P injected intra-arterially but only rarely when the polypeptide was injected intravenously.5 The depressor effects of substance P per se were variable in magnitude and duration as were the inhibitory effects upon nicotinic receptors. The depressor and inhibitory effects of substance P were unrelated.6 There was desensitization to all of these effects of substance P which probably contributed to the variation in the magnitude of the effects observed.7 Substance P had no effect on muscarinic actions of acetyl-beta-methylcholine on the nictitating membrane or blood pressure.8 The results are discussed in relation to the ubiquity of the modulatory actions of substance P on nicotinic receptors and in relation to the possible physiological significance of the action.

Mustard oil excites but does not inhibit nociceptive dorsal horn neurones in the rat: a presumed effect on A-delta fibres.

1. Mustard oil was applied topically in concentrations of 10-20% to the excitatory and inhibitory nociceptive receptive fields in glabrous and hairy skin of the anesthetized rat while recording the activity of nociceptive dorsal horn neurones. The noxious stimulus was radiant heat which is known to activate C-fibres in glabrous and hairy skin. 2. Mustard oil had little effect when applied to glabrous skin and this was attributed to poor penetration of the skin. 3. Mustard oil excited cells in the dorsal horn which were excited by noxious heat in the receptive field on hairy skin. 4. Mustard oil excited cells in the dorsal horn which were inhibited by noxious heat in the receptive field on hairy skin. 5. Inhibitory effects of mustard oil were never seen, even when applied to receptive fields in which noxious heating caused inhibition. 6. The excitatory effects of mustard oil on cells inhibited by noxious heating of the skin are attributed to the reported activation of A-delta fibres which probably masked any C-fibre activation.

Opiates distinguish spinal excitation from inhibition evoked by noxious heat stimuli in the rat: relevance to theories of analgesia.

1. Experiments were performed to test the hypothesis that a significant part of the action of opiates in reducing responses to noxious stimuli is a reduction in the release of neurotransmitter from primary afferent fibres. 2. The effects of locally and systemically administered opiates were examined on the excitatory and gamma-aminobutyric acid (GABA)-mediated inhibitory responses of spinal dorsal horn neurones to noxious heat stimulation in the anaesthetized rat: the inhibitions are thought to involve the same C-fibre afferents as the excitation. 3. Microionophoretically administered morphine reduced the excitatory response i a small proportion of the cells, reduced the background firing in a larger proportion but was ineffective on the inhibition. 4. Intravenously injected morphine (0.5-6 mg kg-1) or etorphine (0.1-2 micrograms kg-1) invariably attenuated the excitation of dorsal horn neurones by noxious stimuli but had no effect on the inhibition. 5. It was concluded that the data do not support the hypothesis that the production of analgesia is due mainly to a reduction in the release of transmitter from primary afferent fibres.

The relative significance of spinal and supraspinal actions in the antinociceptive effect of morphine in the dorsal horn: an evaluation of the microinjection technique.

Large quantities of morphine injected directly into the brainstem of spinal anaesthetized cats inhibited the noxious heat-evoked excitation of dorsal horn neurones. The amounts required were similar to those that were required intravenously in cats with the spinal cord intact or transected. When the spinal cord was intact the amount of morphine microinjected into the brainstem required to inhibit the excitation of dorsal horn neurones was about ten fold less than it was in spinal animals. It is concluded that large, but not small doses of morphine microinjected into the brainstem can exert effects on the spinal cord after first entering the circulation. The effects of small doses are attributed to a local action in the brainstem which causes inhibition of spinal neurones either by activating descending inhibitory neuronal systems or by liberating endogenous substances which reach the spinal cord via the cerebro-spinal fluid. The concentrations of morphine achieved at various distances from the site of injection by the microinjection of microgram quantities and the time courses of the concentration changes were calculated from diffusion equations, assuming diffusion coefficients of 3 or 5 X 10(6) cm2 s-1. The curves obtained closely approximated those obtained experimentally. The concentrations achieved at distances up to 2 mm from the site of injection of 10 micrograms of morphine were calculated to exceed 10(-4)M and the time-courses of these concentration changes were compatible with the time course of inhibition of spinal neurones, or the production of analgesia after microinjection. Such concentrations are vastly in excess of those achieved in the brain after the systemic administration of morphine in analgesic doses. It is concluded that the local effects in the brainstem produced by the microinjection of microgram quantities of morphine have no relevance to the mechanism of analgesia produced by systemic administration.

Safety and immunogenicity of three doses of a Neisseria meningitidis A + C diphtheria conjugate vaccine in infants from Niger.

BACKGROUND: High rates of endemic disease and recurrent epidemics of serogroup A and C meningococcal meningitis continue to occur in sub-Saharan Africa. A meningococcal A + C polysaccharide diphtheria-toxoid-conjugated vaccine may address this issue. METHODS: In Niger three doses of a bivalent meningococcal A + C diphtheria-toxoid-conjugated vaccine (MenD), containing 1, 4 or 16 microg of each polysaccharide per dose, administered at 6, 10 and 14 weeks of age, were compared with Haemophilus influenzae type b-tetanus toxoid-conjugated (PRP-T) vaccine given with the same schedule or with a meningococcal A + C polysaccharide vaccine (MenPS) given at 10 and 14 weeks of age. One blood sample was taken at the time of enrollment (6 weeks of age) and another was taken 4 weeks after the primary series. RESULTS: All doses of MenD were well-tolerated. After the primary series a higher proportion of infants had detectable serum bactericidal activity against serogroup A for each dose of MenD (from 94% to 100%) than for MenPS (31%) or H. influenzae type b-tetanus toxoid-conjugated vaccine (18.9%); P < or = 0.05. Significant differences were also observed for serogroup C MenD 4 microg or MenD 16 microg (100%) vs. MenPS (69.7%) or Haemophilus influenzae type b-tetanus toxoid-conjugated vaccine (24.3%); P < or = 0.05. When MenPS vaccine was given to 11-month-old children, the immune response measured by both enzyme-linked immunosorbent assay and serum bactericidal assay was greater in those previously immunized with MenD than in those immunized with MenPS vaccine. CONCLUSION: MenD was safe among infants in Niger, and immunization led to significantly greater functional antibody activity than with MenPS. The 4-microg dose of MenD for both the A and C serogroups has been selected for further studies.

A microtechnique for measuring red cell osmotic fragility of infants.

Chloramphenicol (D-threo-2-dichloroacetamido-1-p-nitrophenylpropane-1,3-diol) added to blood samples did not alter the observed shift in the red cell osmotic fragility curves as the samples were aged in vitro for 24 hours at 37 degrees C. Nor was the normal rate of loss of 2,3-diphosphoglycerate, ATP, or glutathione from the red cells affected by the presence of chloramphenicol over the same period. Consequently, this bacteriostatic agent can be added to blood samples taken under non-sterile conditions, such as from the heel of an infant, in order to preserve them from the effects of microbial contamination. In this way red cell osmotic fragility results can be obtained on non-sterile samples after their incubation at 37 degrees C for 24 hours. A miniaturisation of the standard osmotic fragility procedure is described, which allows results to be produced from the small, non-sterile samples obtained by heel-prick of infants.

Effect of sulphydryl inhibition on the uptake of transferrin-bound iron by reticulocytes.

Iron transferrin, the highly stable carrier of plasma iron, may be dissociated, under physiological conditions, by sodium thioglycollate, a reaction which involves the formation of iron thioglycollate complexes. This suggested that sulphydryl radicals, which are the active groups in thioglycollate and related compounds, may play a part in the uptake of iron by immature red cells from iron transferrin. If this were so, it could be predicted that the sulphydryl inhibitor, p-hydroxymercuribenzoate, would depress the uptake of iron by reticulocytes. It is demonstrated here that inhibition of uptake of transferrin-bound iron by reticulocytes, which have been exposed to micromolar concentration of p-hydroxymercuribenzoate, is virtually complete. It is suggested that sulphydryl-containing compounds are intimately involved in the process of iron uptake by immature red cells.

Effect of total leucocyte count on whole blood filterability in patients with peripheral vascular disease.

An abnormal filterability of whole blood through micropore membranes in vitro has been reported in peripheral vascular disease and has been thought to indicate abnormal red cell deformability. Blood from 68 patients with symptomatic peripheral vascular disease of varying severity and from 32 age-matched controls without a history of peripheral vascular disease was studied by the technique of whole blood filtration. In agreement with earlier findings, whole blood filterability was significantly reduced in patients with symptoms of vascular disease, but also their total leucocyte count was significantly higher than that of the controls. Variation in leucocyte count was found to affect significantly whole blood filterability, and the abnormal filterability in peripheral vascular disease could be entirely ascribed to this factor and not to an alteration in red cell deformability. The raised leucocyte count was not due to smoking but its cause could not be explained.

Rectal cancer: the Basingstoke experience of total mesorectal excision, 1978-1997.

OBJECTIVE: To examine the role of total mesorectal excision in the management of rectal cancer. DESIGN: A prospective consecutive case series. SETTING: A district hospital and referral center in Basingstoke, England. PATIENTS: Five hundred nineteen surgical patients with adenocarcinoma of the rectum treated for cure or palliation. INTERVENTIONS: Anterior resections (n = 465) with low stapled anastomoses (407 total mesorectal excisions), abdominoperineal resections (n = 37), Hartmann resections (n = 10), local excisions (n = 4), and laparotomy only (n = 3). Preoperative radiotherapy was used in 49 patients (7 with abdominoperineal resections, 38 with anterior resections, 3 with Hartmann resections, and 1 with laparotomy). MAIN OUTCOME MEASURES: Local recurrence and cancer-specific survival. RESULTS: Cancer-specific survival of all surgically treated patients was 68% at 5 years and 66% at 10 years. The local recurrence rate was 6% (95% confidence interval, 2%-10%) at 5 years and 8% (95% confidence interval, 2%-14%) at 10 years. In 405 "curative" resections, the local recurrence rate was 3% (95% confidence interval, 0%-5%) at 5 years and 4% (95% confidence interval, 0%-8%) at 10 years. Disease-free survival in this group was 80% at 5 years and 78% at 10 years. An analysis of histopathological risk factors for recurrence indicates only the Dukes stage, extramural vascular invasion, and tumor differentiation as variables in these results. CONCLUSIONS: Rectal cancer can be cured by surgical therapy alone in 2 of 3 patients undergoing surgical excision in all stages and in 4 of 5 patients having curative resections. In future clinical trials of adjuvant chemotherapy and radiotherapy, strategies should incorporate total mesorectal excision as the surgical procedure of choice.

Measurement of urinary flow rate.

The various methods for measuring urinary flow rate from the first attempt by Rehfisch in 1897 to current techniques are described. The benefits or deficiencies of each method are considered, and it is concluded that while some of the more technically sophisticated pieces of equipment are necessary for the accurate determination of flow rates in the research laboratory, they are not necessarily the most appropriate for use in the consulting office or clinic.

Differential excitatory and inhibitory effects of opiates on non-nociceptive and nociceptive neurones in the spinal cord of the cat.

Morphine, levorphanol, dextrorphan and naloxone were applied microelectrophoretically to cells identified as either having nociceptive inputs or non-nociceptive inputs in the dorsal horn of the cat. Morphine excited non-nociceptive cells and depressed nociceptive cells. Naloxone reversed morphine excitations on non-nociceptive cells, but only reversed about one-third of morphine depressions on nociceptive cells. Levorphanol depressed nociceptive cells, whilst dextrophan ejected with similar currents caused less depression or had no effect. It is concluded that excitation of non-nociceptive cells may constitute a spinal action relevant to the analgesic action of opiates, acting synergistically with a depressant effect on nociceptive neurones.

Systematic mapping of descending inhibitory control by the medulla of nociceptive spinal neurones in cats.

Inhibition descending the spinal cord from the medullary brainstem was systematically mapped in two dimensions in anaesthetized cats. Fifty-four ipsi- and contralateral sites and 27 ipsilateral sites were electrically stimulated with concentric bipolar or with monopolar electrodes, respectively, whilst extracellularly recording firing of dorsal horn neurones to noxious heat. Effective bipolar stimulation, but not monopolar stimulation caused gross lesions at the stimulated sites. There were 3 ipsilateral sites at which descending inhibition was evoked with the smallest stimuli. These areas corresponded to nucleus raphe magnus, nucleus reticularis magnocellularis and the lateral tegmental field. Contralateral stimulation was as effective or more effective than ipsilateral stimulation. The inhibition of dorsal horn neurones was not due to the cardiovascular changes which sometimes accompanied stimulation of the brainstem. The data are discussed in relation to the analgesia which results from stimulating these areas of the brainstem.

The differential effects of 5-hydroxytryptamine, noradrenaline and raphe stimulation on nociceptive and non-nociceptive dorsal horn interneurones in the cat.

The effects of 5-hydroxytryptamine (5-HT), noradrenaline (NA) and stimulation of the inferior central nucleus of the raphe (RN) were examined on nociceptive and non-nociceptive spinal neurones in anaesthetized cats. 5-HT reduced excitation evoked by noxious stimulation, but increased spontaneous firing and firing evoked by DL-homocysteic acid (DLH) on both nociceptive and non-nociceptive cells. NA reduced spontaneous activity, DLH-evoked excitation and excitation evoked by a noxious stimulus on nociceptive neurones, but had little action on non-nociceptive units. RN inhibited spontaneous, stimulus-evoked and DLH-evoked firing of nociceptive cells and caused briefer inhibitions of non-nociceptive cells. Excitatory effects were also observed. Strychnine antagonized short-duration inhibitions from RN of non-nociceptive cells responding to hair movement, but failed to antagonize any of the other effects of RN. No antagonism of the inhibitory effect of RN was observed with phenoxybenzamine, phentolamine, sotalol, bicuculline or methysergide. However, methysergide antagonized some excitatory effects of 5-HT and RN, but also produced non-specific actions on some cells. It was concluded that, although glycine may mediate some of the brief duration inhibitions evoked by RN, the longer duration inhibitions were unlikely to have been mediated by either glycine or GABA. 5-HT may be a mediator of raphe-spinal actions but may have presynaptic inhibitory actions coupled with postsynaptic excitatory effects. NA could mediate some descending inhibition of nociceptive neurones.