Actigraphic assessment of periodic leg movements in patients with restless legs syndrome

The diagnosis of restless legs syndrome (RLS) relies upon diagnostic criteria which are based on history only, and dopaminergic treatment is not normally the first choice of treatment for all patients. It would be worthwhile to identify patients non‐responsive to dopaminergic treatment beforehand, because they may suffer from a restless legs‐like syndrome and may require alternative treatment. We included retrospectively 24 adult patients fulfilling the four essential criteria for restless legs and 12 age‐matched healthy controls. They were investigated by ambulatory actigraphy from both legs over three nights, and patients started treatment with dopamine agonists after this diagnostic work‐up. We examined 12 responders to dopaminergic treatment and 12 non‐responders and studied the association between response to dopaminergic treatment and the periodic limb movement index (PLMI) as assessed with actigraphy. Demographic characteristics, excessive daytime sleepiness and fatigue at baseline were similar in all three groups. Baseline RLS severity was similar between responders and non‐responders [International Restless Legs Severity Scale (IRLS): 25 ± 9 and 24 ± 8]. Group comparisons of PLMI before treatment initiation showed significant differences between the three groups. Post‐hoc pairwise comparisons revealed that healthy controls had significantly lower PLMI (4.9 ± 4.5) than responders (29.3 ± 22.7) and non‐responders (13.3 ± 11.2). Similarly, the PLMI in responders was lower than in non‐responders. PLMI day‐to‐day variability did not differ between responders and non‐responders and there was no correlation between treatment effect, as assessed by the decrease of the IRLS and baseline PLMI. Our retrospective study indicates that actigraphy to assess periodic limb movements may contribute to a better diagnosis of dopamine‐responsive restless legs syndrome.     

Epidemiology of restless legs syndrome in Korean adults

STUDY OBJECTIVES: To investigate the prevalence of restless legs syndrome (RLS) in Korea. DESIGN: A large population-based telephone interview method using the Korean version of the Johns Hopkins telephone diagnostic interview for the RLS. SETTING: A computer aided telephone interview method. PARTICIPANTS: A total of 5,000 subjects (2,470 men and 2,530 women) were interviewed in depth. A representative sample aged 20 to 69 years was constituted according to a stratified, multistage random sampling method. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Of the respondents, 373 respondents (7.5%) of the population (pop) met the criteria for the definite or probable RLS groups: 194 (3.9% of pop) respondents fulfilled the criteria for definite RLS and 179 (3.6% of pop) respondents fulfilled the criteria for probable RLS. The prevalence of RLS was generally higher for women than men (4.4% vs. 3.3% for definite, 8.7% vs. 6.2% for definite plus probable). About 90% of RLS individuals were experiencing symptoms at the time of the interview and this was similar for both RLS groups. Seventy-four respondents (1.48%) reported symptoms were moderately or severely distressing and were therefore classified as RLS "sufferers." Of those with a diagnosis of RLS sufferer, 24.3% reported being treated for their symptoms, compared to 12.4% of RLS not designated a "sufferer." CONCLUSION: RLS is common and underdiagnosed in Korea with nearly 1% of the population reporting disturbed sleep related to their RLS. These results are comparable to other countries.     

A potential role for zinc in restless legs syndrome

Study ObjectivesEvaluate serum and brain noniron metals in the pathology and genetics of restless legs syndrome (RLS).MethodsIn two independent studies (cohorts 1 and 2), in which subjects either remained on medications or tapered off medications, we analyzed serum levels of iron, calcium, magnesium, manganese, copper, and zinc both in RLS patients and controls, and assessed the prevalence of the MEIS1 and BTBD9 risk alleles previously established through genome-wide association studies. Human brain sections and a nematode genetic model were also quantified for metal levels using mass spectrometry.ResultsWe found a significant enrichment for the BTBD9 risk genotype in the RLS affected group compared to control (p = 0.0252), consistent with previous literature. Serum (p = 0.0458 and p = 0.0139 for study cohorts 1 and 2, respectively) and brain (p = 0.0413) zinc levels were significantly elevated in the RLS patients versus control subjects.ConclusionWe show for the first time that serum and brain levels of zinc are elevated in RLS. Further, we confirm the BTBD9 genetic risk factor in a new population, although the zinc changes were not significantly associated with risk genotypes. Zinc and iron homeostasis are interrelated, and zinc biology impacts neurotransmitter systems previously linked to RLS. Given the modest albeit statistically significant increase in serum zinc of ~20%, and the lack of association with two known genetic risk factors, zinc may not represent a primary etiology for the syndrome. Further investigation into the pathogenetic role that zinc may play in restless legs syndrome is needed.     

Association between irritable bowel syndrome and restless legs syndrome in the general population

This study aimed to explore the association between restless legs syndrome and irritable bowel syndrome in an epidemiological cohort. We included 3365 adults, of whom 1602 were female (age 52.5 ± 7.5 years), who had participated in the Korean Genome and Epidemiology Study (2005–2006). The diagnosis of restless legs syndrome was based on the criteria proposed by the International Restless Legs Syndrome Study Group, and irritable bowel syndrome was defined according to the Rome II criteria. The prevalence of each condition was determined and their association was tested by logistic regression analysis. Age, sex, haemoglobin concentration, renal insufficiency, use of medications and depressive mood were all adjusted for. The prevalence of restless legs syndrome and irritable bowel syndrome was 4.5 and 11.1%, respectively. Irritable bowel syndrome was more prevalent in the group with restless legs syndrome (24.0 versus 10.5%, P < 0.001). Subjects with restless legs syndrome were older (54.2 ± 8.4 versus 52.4 ± 7.4, P = 0.006) and more depressive (26.7 versus 12.5%, P < 0.001), and were predominantly female (57.3 versus 47.2%, P = 0.015), had more frequent insomnia symptoms (44.0 versus 28.2%, P < 0.001), had lower haemoglobin concentration (13.7 ± 1.5 versus 14.1 ± 1.6 g dL^?1P = 0.004) and higher highly sensitive C‐reactive protein (1.8 ± 5.1 versus 1.4 ± 2.9 mg dL^?1, P = 0.08). The adjusted odds ratio of restless legs syndrome in relation to irritable bowel syndrome was 2.59 (1.74–3.85, P < 0.001). Irritable bowel syndrome appeared to be associated with restless legs syndrome independently from other major risk factors for restless legs syndrome. Searching for the mechanisms underlying this association is indicated.     

Periodic leg movements during sleep in narcoleptic patients with or without restless legs syndrome

We compared periodic and non‐periodic leg movements during sleep and polysomnography in patients with narcolepsy with cataplexy (NC) with or without restless legs syndrome (RLS) with matched idiopathic RLS (iRLS) and control subjects. We enrolled 100 patients with NC: 17 having RLS were compared with 34 sex‐ and age‐matched patients without RLS and with 17 normal controls and 17 iRLS subjects. Periodic leg movements were highest in iRLS and lowest in controls, with those in NC with RLS very close to iRLS, but higher than those in NC without RLS. The periodicity indexes showed the highest value in iRLS followed by NC with or without RLS and, finally, by controls. The inter‐leg movement intervals peaked between 10 and 50 s in NC with RLS and in iRLS, the former did not display the nocturnal gradual decrease of periodic leg movements typical of iRLS. Periodic leg movements during sleep and polysomnography displayed specific features in RLS and NC, respectively, with NC with RLS showing an intermediate pattern. Even if RLS is only detected by targeted interview in NC, its frequency and impact on night‐time sleep architecture and continuity suggest that this condition should be routinely searched for in NC.     

Indications for performing polysomnography in the diagnosis and treatment of restless legs syndrome

Summary Restless legs syndrome (RLS) is diagnosed clinically by evaluating the patient's complaints. Diagnostic criteria based on the clinical symptoms were defined by the International Restless Legs Syndrome Study Group. Laboratory and/or neurophysiological assessments can differentiate a primary (idiopathic) RLS from a secondary (associated with an other disease) RLS. Some differential diagnostic and therapeutic issues may, however, require polysomnographic assessment. An investigation in the sleep laboratory should be considered in the following cases: 1) in patients with "atypical" RLS symptoms to support the diagnosis, before pharmacological treatment is begun; 2) in patients on sufficient dopaminergic treatment but still suffering from sleep disturbance, in order to exclude other sleep-related disorders; 3) in patients with mild RLS but marked daytime sleepiness as the main symptom; 4) to support the diagnosis in young patients with severe RLS before dopaminergic treatment is begun or in patients with severe RLS before the start of a treatment with opiates; 5) in patients with RLS and sleep-related respiratory disorders; 6) and finally in patients who are involved in a formal expert's opinion report. Further indications may exist in exceptional cases. A recommendation for performing polysomnography should be always made by a clinician experienced in the diagnosis and treatment of sleep disorders.     

Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H₂-receptor antagonists (H₂A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge–Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H₂A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13–1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03–1.95; p = 0.03) and H₂A (OR = 1.56; CI, 1.10–2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H₂As (OR = 1.29; CI, 1.20–1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17–1.38; p < 0.001), but not H₂As alone (OR = 1.18; CI, 0.92–1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H₂A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H₂A in populations at particular risk for RLS.     

Novel assessment of microvascular changes in idiopathic restless legs syndrome (Willis–Ekbom disease)

Many patients with restless legs syndrome (Willis–Ekbom disease) complain of burning sensations in their feet associated with the desire to move, such that they seek cooler environments. This pilot study aimed to characterise the microvascular skin changes in 12 patients with restless legs syndrome compared with 12 age‐ and sex‐matched controls. Patients with moderate or severe restless legs syndrome and controls underwent detailed thermovascular assessment in a controlled temperature room at three different stages (normothermic phase 23 °C, hot phase 30 °C, cold phase 18 °C). Microvascular activity was recorded during all phases by bilateral great toe laser‐Doppler flowmetry and also by whole‐body thermography. Patient and control measurements were compared. The study protocol was well tolerated. Parameters extracted from the laser‐Doppler flowmetry measurements were used to model a logistic function using binary logistic regression. This demonstrated a statistically significant difference between patients with restless legs syndrome and healthy controls (P < 0.001). Visual inspection of the body thermography image sequences showed increased lower limb movement in patients with restless legs syndrome patients compared with controls. Thermography analysis also showed significant differences between foot temperatures in patients with restless legs syndrome compared with controls during the hot phase (P = 0.011). Notably, patients with restless legs syndrome had more uniform foot temperatures, whereas controls had a wider variability in surface temperature across the feet. This novel study demonstrates impaired microvascular circulation in patients with restless legs syndrome in comparison to matched controls and a potential mechanism for the sensation of burning feet. The protocol also provides an experimental paradigm to test therapeutic interventions for the future.     

Symptom‐related changes in current perception threshold of restless legs syndrome

Few studies have investigated the mechanisms responsible for the symptoms of restless legs syndrome (RLS). However, these studies were mainly performed during the asymptomatic period and therefore their findings might not apply to changes in sensory processing that occur during the symptomatic period. The objective of this study was to investigate the function of sensory nerve fibres in RLS patients using the current perception threshold (CPT) test during the daytime and in the presence of symptoms. Ninety‐three patients with RLS and 34 healthy controls were included in the study. RLS patients were further divided into two subgroups, those who were experiencing RLS symptoms during the CPT test (symptom+) and those without symptoms (symptom?). Demographic data, RLS rating scale score and visual analogue scale were collected. Of the 127 enrolled subjects, CPT values were significantly lower in RLS patients than in controls for all three frequencies. Among the control and RLS subgroups (53 symptom+, 40 symptom?), symptom+ patients showed lower CPT values than controls. This finding indicates a relative hyperaesthetic state in the sensory afferents of peripheral nerves in symptom+ patients. There were no significant differences between the symptom? group and controls. The significantly lower CPT values for all three frequencies in symptom+ patients suggest that central sensory processing disturbance of sensory nerve fibres’ input may be involved in the development of symptoms in RLS patients.     

Prevalence of restless legs syndrome and sleep quality in carriers of the fragile X premutation

This study examined the relationship between the fragile X premutation and restless legs syndrome (RLS). Demographic, medical history and survey responses related to sleep were collected from 213 participants (127 carriers and 86 age matched controls). Subjects were asked about the presence of the four formal diagnostic criteria for RLS. Individuals with the premutation were 1.9 times as likely to meet criteria for RLS (95% CI 1.1–3.2, p = 0.025) as controls. Premutation carriers with RLS also experienced significantly worse symptoms than matched controls with adjusted mean scores of 15.1 ± 8.8 vs 7.9 ± 4.4, respectively on the International Restless Legs Scale (IRLS). As markers for domains of sleep disturbance, all subjects completed the Epworth Sleepiness Scale (ESS), the Insomnia Severity Index (ISA) and the Pittsburgh Sleep Quality Index (PSQI). Premutation carriers demonstrated significantly more pathology on these tests except for the ESS where there was a trend towards increased daytime sleepiness in carriers. RLS joins a host of other conditions that should be carefully screened for in those carrying the fragile X premutation and sleep should be a focus for clinicians providing care to them.     

Socio-economic risk factors for incident restless legs syndrome in the general population

Few and controversial data exist about the relationship between socio‐economic status and restless legs syndrome, and prospective analyses are lacking. We aimed to explore the associations between socio‐economic factors and incident restless legs syndrome in the general population. Two prospective population‐based cohort studies were conducted: the Dortmund Health Study with a mean follow‐up of 2.2 years; and the Study of Health in Pomerania with a mean follow‐up of 5.2 years. The studies included 1312 subjects and 4308 subjects, respectively. Restless legs syndrome was assessed twice according to the standard minimal criteria. The modified Winkler Index of social class, education, job status, partnership and income were assessed by interviews at baseline. The risk of restless legs syndrome associated with each socio‐economic factor was estimated by multivariable logistic regression adjusted for behavioural factors and co‐morbidities. Female gender, being retired and unemployment were independent risk factors of incident restless legs syndrome in both studies. Low level of education and income were independently associated with incident restless legs syndrome only in the Dortmund Health Study, but not in the other study. Migrational background and shiftwork were further independent risk factors of restless legs syndrome that were only assessed in the Dortmund Health Study. People with less favourable socio‐economic situation are at an increased risk of developing restless legs syndrome. Behavioural variables and co‐morbidities did not explain this association, thus further studies are required to reveal the mechanism behind the proposed relationship.     

Association of incident restless legs syndrome with outcomes in a large cohort of US veterans

Restless legs syndrome is a common sleep disorder, but there is a paucity of large cohort studies examining the association of restless legs syndrome with clinical outcomes, including all‐cause mortality, incident coronary heart disease, stroke and chronic kidney disease. From a nationally representative prospective cohort of over 3 million US veterans [93% male, median follow‐up time of 8.1 years (interquartile range: 7.0–8.5 years)] with baseline estimated glomerular filtration rate ≥60 mL min^?1 1.73 m^?2, a propensity‐matched cohort of 7392 patients was created, and the association between incident restless legs syndrome and the following was examined: (1) all‐cause mortality; (2) incident coronary heart disease; (3) incident strokes; and (4) incident chronic kidney disease defined as estimated glomerular filtration rate <60 mL min^?1 1.73 m^?2. Associations were examined using Cox models. The mean ± SD age of the propensity‐matched cohort at baseline was 59 ± 12 years; 89 and 8% of patients were white and black, respectively; 31% of the patients were diabetic; and the mean baseline estimated glomerular filtration rate was 83.9 ± 15.1 mL min^?1 1.73 m^?2. Propensity matching resulted in a balanced cohort, with the disappearance in baseline differences in comorbidities. Compared with restless legs syndrome‐negative patients, incident restless legs syndrome was associated with 88% higher mortality risk [hazard ratio and 95% confidence interval: 1.88 (1.70–2.08)], and almost four times higher risk of coronary heart disease and stroke [hazard ratio: 3.97 (3.26–4.84) and 3.89 (3.07–4.94), respectively]. The risk of incident chronic kidney disease was also significantly higher in incident restless legs syndrome patients [hazard ratio: 3.17 (2.74–3.66)] compared with restless legs syndrome‐negative counterparts. In this large and contemporary cohort of US veterans, incident restless legs syndrome was associated with higher risk of mortality, incident coronary heart disease, stroke and chronic kidney disease.     

Peculiar lifespan changes of periodic leg movements during sleep in restless legs syndrome

The objective of this observational cohort study was to analyse the age‐related changes of periodic leg movements during sleep using the newest international scoring rules, to expand past analyses, including patients in the paediatric age range, and also to analyse the changes of short‐interval and isolated leg movements during sleep throughout the lifespan. One hundred and sixty‐five patients (84 women) with restless legs syndrome were recruited in the following age groups: 16 preschoolers (≤5 years of age), 29 school‐age children (6–12 years), 19 adolescents (13–17 years), 17 young adults (19–40 years), 47 adults (41–60 years) and 37 seniors (>60 years). Total, periodic, short‐interval and isolated leg movements during sleep and periodicity indexes were obtained by polysomnography. The total index showed (quartic polynomial interpolation) a decrease before 10 years, followed by a steady increase up to 30 years, a relatively stable period until 60 years, and a final increase up to 80 years. This course was almost entirely due to changes in periodic movements. Isolated movements did not change significantly and short‐interval movements showed only an increase in seniors. Our study indicates that, in restless legs syndrome, the total index shows a peculiar and unique course throughout the lifespan, mainly due to periodic movements. These age‐related changes may mirror developmental changes in network complexity known to occur in dopaminergic circuits. These data further confirm the need to better assess the periodicity of leg movements in sleep during the human development period, in order to obtain clinically useful information.     

A time sequence analysis of the relationship between cardiovascular risk factors,vascular diseases and restless legs syndrome in the general population

Previous cross‐sectional studies regarding the association of restless legs syndrome (RLS) with cardiovascular morbidity are controversial. Our aim was to evaluate prospectively the relationship of cardiovascular risk factors and vascular diseases with incident RLS in the general population. The results are from two prospective population‐based cohort studies: the Dortmund Health Study (n = 1312, median follow‐up of 2.1 years) and the Study of Health in Pomerania (n = 4308, median follow‐up of 5.0 years). RLS status was assessed twice according to the minimal criteria. Diabetes, hypertension, myocardial infarction and stroke, as well as currently taken medications, were assessed as self‐reports. Body mass index and serum total cholesterol were also measured. The independent risks associated with each outcome were estimated by multivariable logistic regression models adjusted for comorbidities and behavioural factors. Obesity was an independent risk factor of incident RLS in the Dortmund Health Study, and higher body mass index was an independent risk factor in both studies. Diabetes, hypertension and hypercholesterolaemia were independent predictors of incident RLS in the Study of Health in Pomerania. The vascular comorbidity index, defined by the number of concurrent cardiovascular risk factors and vascular diseases, showed a positive association with incident RLS in both studies. RLS at baseline was not a significant predictor of any subsequent cardiovascular risk factors and/or vascular diseases in any of the studies. Cardiovascular risk factors and diseases predict the subsequent development of RLS in the general population. The presence of RLS is not a significant risk factor of cardiovascular morbidity.     

Circadian variation in neuroendocrine response to L-dopa in patients with restless legs syndrome

STUDY OBJECTIVE: To investigate circadian changes in dopaminergic function by means of a neuroendocrine challenge (growth hormone and prolactin responses to an acute oral administration of L-dopa) in patients with idiopathic restless legs syndrome (RLS) and controls. DESIGN: Randomized administration of the L-dopa neuroendocrine challenge. SETTING: Sleep disorders laboratory at a 500-bed academic hospital. PATIENTS OR PARTICIPANTS: Twelve patients diagnosed with idiopathic RLS and 12 age- and sex-matched healthy controls. INTERVENTIONS: Following a comprehensive evaluation that included nocturnal polysomnographic study, all participants underwent the L-dopa neuroendocrine challenge on 2 occasions (11 am and 11 pm). Subjects were previously randomly assigned to the time of first challenge (11 am or 11 pm). On each occasion, subjects took 200 mg of L-dopa (plus 50 mg carbidopa) by mouth. Blood was drawn 20 minutes and 5 minutes before administration of the drug, as well as 15, 30, 45, 60, 75, 90, 102, and 120 minutes after administration. RESULTS: Prechallenge levels of plasma values of growth hormone or prolactin did not differ in the 2 subject groups. Following only the nighttime administration of L-dopa, RLS patients manifested a more pronounced inhibition of prolactin release and an increase in growth hormone secretion. Prolactin plasma levels were significantly correlated to the periodic limb movement index on the polysomnogram. CONCLUSIONS: These findings may reflect enhanced circadian variations in dopaminergic function and support an increased sensitivity at night of dopamine receptors in patients with RLS.     

No significance of the COMT valmet polymorphism in restless legs syndrome

The catechol-O-methyltransferase (COMT) val¹⁵⁸met polymorphism, which codes for the substitution of valine (val) by methionine (met) leading to a reduced COMT activity in homo- or heterozygous individuals, is associated with individual pain sensitivity and dopaminergic responses in Parkinson's disease as well as with various chronic painful diseases. Recent investigations support the notion of an alteration of the medial pain pathway as well as of the descending inhibitory control system in restless legs syndrome (RLS), that both involve dopaminergic transmission as well. Thus, the distribution of the COMT val¹⁵⁸met polymorphism was assessed in 298 RLS patients and compared with 135 healthy controls in relation to sex, age of onset and family history. The data revealed no significant differences in the distribution of the COMT val¹⁵⁸met polymorphism in RLS patients compared with the control group, also when the heterozygous and the homozygous group containing the ¹⁵⁸met allele were combined. In addition, sex, age of onset and family history were not associated with the COMT val¹⁵⁸met polymorphism in this German population of RLS patients. The present study adds to previous mostly negative investigations on the genetic determination of dopaminergic transmission in RLS, which have – so far – only detected an association of the MAO-A activity and RLS in females in a French-Canadian population. Further investigations assessing the different COMT haplotypes and experimental and clinical parameters are nevertheless warranted.     

Dilution of candidates: the case of iron-related genes in restless legs syndrome

Restless legs syndrome (RLS) is a common multifactorial disease. Some genetic risk factors have been identified. RLS susceptibility also has been related to iron. We therefore asked whether known iron-related genes are candidates for association with RLS and, vice versa, whether known RLS-associated loci influence iron parameters in serum. RLS/control samples (n=954/1814 in the discovery step, 735/736 in replication 1, and 736/735 in replication 2) were tested for association with SNPs located within 4 Mb intervals surrounding each gene from a list of 111 iron-related genes using a discovery threshold of P=5 × 10⁻⁴. Two population cohorts (KORA F3 and F4 with together n=3447) were tested for association of six known RLS loci with iron, ferritin, transferrin, transferrin-saturation, and soluble transferrin receptor. Results were negative. None of the candidate SNPs at the iron-related gene loci was confirmed significantly. An intronic SNP, rs2576036, of KATNAL2 at 18q21.1 was significant in the first (P=0.00085) but not in the second replication step (joint nominal P-value=0.044). Especially, rs1800652 (C282Y) in the HFE gene did not associate with RLS. Moreover, SNPs at the known RLS loci did not significantly affect serum iron parameters in the KORA cohorts. In conclusion, the correlation between RLS and iron parameters in serum may be weaker than assumed. Moreover, in a general power analysis, we show that genetic effects are diluted if they are transmitted via an intermediate trait to an end-phenotype. Sample size formulas are provided for small effect sizes.     

Inhibitory effects on flexor reflexes in patients with a complete spinal cord lesion

Summary The inhibitory effects on flexors of electrical stimulation of a distal peripheral nerve were investigated in 7 paraplegic patients having a complete spinal cord section. The stimuli (3–50 mA) were applied to the sural nerve. Their effects were investigated on: 1) the ipsi- and contralateral H reflex of the Tibialis Anterior (TA); 2) the continuous EMG activity reflexly elicited in TA by a sustained pinch of the foot and 3) on the reflexes evoked in TA by contralateral sural nerve stimulation. Sural nerve stimulation induced two peaks of facilitation of the ipsilateral TA H reflex that could be replaced by inhibition as the stimulus intensity was increased. The comparison of the effect on H reflexes and the EMG activity suggests presynaptic inhibition of Ia fibres at time intervals longer than 300 ms. The stimulation could depress the sustained EMG reflex activity and induce a period of silence whose duration increased with the intensity of the stimulation. As shown in a previous study, a sural nerve stimulation induced a reflex in TA with a prolonged (more than 130 ms) latency. This late reflex could be selectively inhibited by a contralateral sural nerve stimulation, probably at an interneuronal level. These results confirm that the late reflex in TA is similar to the one observed after Flexor Reflex Afferent (FRA) stimulation in the acute spinal cat with DOPA. In addition, they show that at least some part of the half centre organization which has been described in the acute spinal cat with DOPA is also present in the human spinal cord chronically deprived of supraspinal control.     

Intrathecal neurokinin A facilitates the spinal nociceptive flexor reflex evoked by thermal and mechanical stimuli and synergistically interacts with substance P

The neuropeptide neurokinin A was injected intrathecally and its effect on the spinal nocifensive flexor reflex was examined. The reflex, which was evoked by electrical, thermal or mechanical stimulation of the foot and was recorded from the ipsilateral hamstring muscles, was substantially facilitated by 7 pmol intrathecally injected neurokinin A. The facilitatory effect of neurokinin A to thermal stimulation was, however, significantly stronger than to electrical or mechanical stimuli. Furthermore, co-administration of neurokinin A with substance P induced a significant synergistic facilitation of the reflex. It is suggested that neurokinin A, like substance P, may be released in association with activation of polymodal C-nociceptors.