Migraine and Its Association with Hyperactivity of Cell Membranes in the Course of Latent Magnesium Deficiency-Preliminary Study of the Importance of the Latent Tetany Presence in the Migraine Pathogenesis.

So far, there is no consistent and convincing theory explaining the pathogenesis of migraines. Vascular disorders, the effect of oxidative stress on neurons, and the contribution of magnesium-calcium deficiencies in triggering cortical depression and abnormal glutaminergic neurotransmission are taken into account. However, there are no reliable publications confirming the role of dietary deficits of magnesium and latent tetany as factors triggering migraine attacks. The aim of the study was to evaluate the influence of latent magnesium deficiency assessed with the electrophysiological tetany test on the course of migraine. The study included: a group of 35 patients (29 women and six men; in mean age 41 years) with migraine and a control group of 24 (17 women and seven men; in mean age 39 years) healthy volunteers. Migraine diagnosis was based on the International Headache Society criteria, 3rd edition. All patients and controls after full general and neurological examination were subjected to a standard electrophysiological ischemic tetany test. Moreover, the level of magnesium in blood serum was tested and was in the normal range in all patients. Then, the incidence of a positive tetany EMG test results in the migraine group and the results in the subgroups with and without aura were compared to the results in the control group. Moreover, the relationship between clinical markers of spasmophilia and the results of the tetany test was investigated in the migraine group. As well as the relationship between migraine frequency and tetany test results. There was no statistically significant difference in the occurrence of the electrophysiological exponent of spasmophilia between the migraine and control group. Neither correlation between the occurrence of clinical symptoms nor the frequency of migraine attacks and the results of the tetany test was stated (p > 0.05). However, there was an apparent statistical difference between the subgroup of migraine patients with aura in relation to the control group (p < 0.05). The result raises hope to find a trigger for migraine attacks of this clinical form, the more that this factor may turn out to be easy to supplement with dietary supplementation.

Neuromuscular tetanic hyperexcitability syndrome associated to a heterozygous Kv1.1 N255D mutation with normal serum magnesium levels.

Mutations of the main voltage-gated K channel members Kv1.1 are linked to several clinical conditions, such as periodic ataxia type 1, myokymia and seizure disorders. Due to their role in active magnesium reabsorption through the renal distal convoluted tubule segment, mutations in the KCNA1 gene encoding for Kv1.1 has been associated with hypomagnesemia with myokymia and tetanic crises. Here we describe a case of a young female patient who came to our attention for a history of muscular spasms, tetanic episodes and muscle weakness, initially misdiagnosed for fibromyalgia. After a genetic screening she was found to be carrier of the c.736A > G (p.Asn255Asp) mutation in KCNA1, previously described in a family with autosomal dominant hypomagnesemia with muscular spasms, myokymia and tetanic episodes. However, our patient has always presented normal serum and urinary magnesium values, whereas she was affected by hypocalcemia. Calcium supplementation gave only partial clinical benefit, with an improvement on tetanic episodes yet without a clinical remission of her spasms, whereas magnesium supplementation worsened her muscular symptomatology.

Delayed expression of activity-dependent gating switch in synaptic AMPARs at a central synapse.

Developing central synapses exhibit robust plasticity and undergo experience-dependent remodeling. Evidently, synapses in sensory systems such as auditory brainstem circuits mature rapidly to achieve high-fidelity neurotransmission for sound localization. This depends on a developmental switch in AMPAR composition from slow-gating GluA1-dominant to fast-gating GluA4-dominant, but the mechanisms underlying this switch remain unknown. We hypothesize that patterned stimuli mimicking spontaneous/sound evoked activity in the early postnatal stage drives this gating switch. We examined activity-dependent changes in evoked and miniature excitatory postsynaptic currents (eEPSCs and mEPSCs) at the calyx of Held synapse by breaking through the postsynaptic membrane at different time points following 2 min of theta burst stimulation (TBS) to afferents in mouse brainstem slices. We found the decay time course of eEPSCs accelerated, but this change was not apparent until > 30 min after TBS. Histogram analyses of the decay time constants of mEPSCs for naive and tetanized synapses revealed two populations centered around τfast ≈ 0.4 and 0.8 ms, but the relative weight of the τ0.4 population over the τ0.8 population increased significantly only in tetanized synapses. Such changes are blocked by NMDAR or mGluR1/5 antagonists or inhibitors of CaMKII, PKC and protein synthesis, and more importantly precluded in GluA4-/- synapses, suggesting GluA4 is the substrate underlying the acceleration. Our results demonstrate a novel form of plasticity working through NMDAR and mGluR activation to trigger a gating switch of AMPARs with a temporally delayed onset of expression, ultimately enhancing the development of high-fidelity synaptic transmission.

Muscle dysfunction in a zebrafish model of Duchenne muscular dystrophy.

Sapje zebrafish lack the protein dystrophin and are the smallest vertebrate model of Duchenne muscular dystrophy (DMD). Their small size makes them ideal for large-scale drug discovery screens. However, the extent that sapje mimic the muscle dysfunction of higher vertebrate models of DMD is unclear. We used an optical birefringence assay to differentiate affected dystrophic sapje larvae from their unaffected siblings and then studied trunk muscle contractility at 4-7 days postfertilization. Preparation cross-sectional area (CSA) was similar for affected and unaffected larvae, yet tetanic forces of affected preparations were only 30-60% of normal. ANCOVA indicated that the linear relationship observed between tetanic force and CSA for unaffected preparations was absent in the affected population. Consequently, the average force/CSA of affected larvae was depressed 30-70%. Disproportionate reductions in twitch vs. tetanic force, and a slowing of twitch tension development and relaxation, indicated that the myofibrillar disorganization evident in the birefringence assay could not explain the entire force loss. Single eccentric contractions, in which activated preparations were lengthened 5-10%, resulted in tetanic force deficits in both groups of larvae. However, deficits of affected preparations were three- to fivefold greater at all strains and ages, even after accounting for any recovery. Based on these functional assessments, we conclude that the sapje mutant zebrafish is a phenotypically severe model of DMD. The severe contractile deficits of sapje larvae represent novel physiological endpoints for therapeutic drug screening.

[Latent tetany in child, electrophysiologico-clinical study]. / Dziecko z tezyczka utajona, studium kliniczno-neurofizjologiczne.

Tetany is the abnormal state of increased neuromuscular excitability. It is manifested with muscle cramps and spasms, usually associated with abnormal calcium metabolism. This state can be devided into two main types: tetany with clinical manifestaton (hypocalcemic) and occurred more frequently latent tetany (normocalcemic). In this study was presented the case of a child with electrophysiological and clinical manifestation of latent tetany. We report a case of a female patient who was admitted to the Pediatric Neurology Department in the year 2015. Some clinical, biochemical and neurophysiological results have been analyzed.

Chvostek's sign in paediatric practice.

Chvostek's Sign was first described in 1876, as a clinical clue associated with patients who suffered from latent tetany, and is induced by percussion of the angle of the jaw. However, over the years many clinicians have called into question the strength of the association with latent tetany, particularly in paediatric practice. This review examines the variation in techniques used to elicit the sign in studies conducted on this phenomenon in children as well as how differences in the classification of a positive Chvostek's sign have lead to varied reports on the strength of the association. Furthermore, an appraisal of the literature regarding the proposed mechanism of Chvostek's sign is reported alongside analysing other diseases which have been associated with Chvostek's sign to uncover any unifying mechanism for the presence of this clinical sign in children.

Effects of pre-irradiation of low-level laser therapy with different doses and wavelengths in skeletal muscle performance, fatigue, and skeletal muscle damage induced by tetanic contractions in rats.

This study aimed to evaluate the effects of low-level laser therapy (LLLT) immediately before tetanic contractions in skeletal muscle fatigue development and possible tissue damage. Male Wistar rats were divided into two control groups and nine active LLLT groups receiving one of three different laser doses (1, 3, and 10 J) with three different wavelengths (660, 830, and 905 nm) before six tetanic contractions induced by electrical stimulation. Skeletal muscle fatigue development was defined by the percentage (%) of the initial force of each contraction and time until 50 % decay of initial force, while total work was calculated for all six contractions combined. Blood and muscle samples were taken immediately after the sixth contraction. Several LLLT doses showed some positive effects on peak force and time to decay for one or more contractions, but in terms of total work, only 3 J/660 nm and 1 J/905 nm wavelengths prevented significantly (p < 0.05) the development of skeletal muscle fatigue. All doses with wavelengths of 905 nm but only the dose of 1 J with 660 nm wavelength decreased creatine kinase (CK) activity (p < 0.05). Qualitative assessment of morphology revealed lesser tissue damage in most LLLT-treated groups, with doses of 1-3 J/660 nm and 1, 3, and 10 J/905 nm providing the best results. Optimal doses of LLLT significantly delayed the development skeletal muscle performance and protected skeletal muscle tissue against damage. Our findings also demonstrate that optimal doses are partly wavelength specific and, consequently, must be differentiated to obtain optimal effects on development of skeletal muscle fatigue and tissue preservation. Our findings also lead us to think that the combined use of wavelengths at the same time can represent a therapeutic advantage in clinical settings.

[Electrophysiological analysis of functional state of spinal cord motoneurons in rats with parathyroprivous tetany].

In normal rats and of those with parathyroprivous (hypocalcemic) tetany the comparative analysis of background activity (BA), tetanic and posttetanic increase and decrease of frequency of spinal cord (SC) motoneurons (MNs) responses under high-frequency (50, 100Hz) stimulation (HFS) of flexor (G) and extensor (P) hind-limb nerves have been conducted. The on-line selection and program analysis of the spikes was produced. On the 3-7 and 21-22 days of development of acute and chronic tetany, respectively, the significant tetanic and posttetanic changes of MNs activity without meaningful changes in BA was registered. Along with the abrupt increase of excitatory manifestation of activity to HFS in a period of development of acute tetany was observed their relative weakening in animals with chronic tetany. Simultaneously the weakening or total disappearance of depressor reaction, especially expressed in the period of development of acute tetany was noted. It was concluded on the causal dependence of the parathyroprivous convulsions due to disturbances of correlation of inhibitory-excitatory processes in SC MNs.

Effects of an immunosuppressive treatment in the GRMD dog model of Duchenne muscular dystrophy.

The GRMD (Golden retriever muscular dystrophy) dog has been widely used in pre-clinical trials targeting DMD (Duchenne muscular dystrophy), using in many cases a concurrent immune-suppressive treatment. The aim of this study is to assess if such a treatment could have an effect on the disease course of these animals. Seven GRMD dogs were treated with an association of cyclosporine A (immunosuppressive dosage) and prednisolone (2 mg/kg/d) during 7 months, from 2 to 9 months of age. A multi-parametric evaluation was performed during this period which allowed us to demonstrate that this treatment had several significant effects on the disease progression. The gait quality as assessed by 3D-accelerometry was dramatically improved. This was consistent with the evolution of other parameters towards a significant improvement, such as the clinical motor score, the post-tetanic relaxation and the serum CK levels. In contrast the isometric force measurement as well as the histological evaluation argued in favor of a more severe disease progression. In view of the disease modifying effects which have been observed in this study it should be concluded that immunosuppressive treatments should be used with caution when carrying out pre-clinical studies in this canine model of DMD. They also highlight the importance of using a large range of multi-parametric evaluation tools to reliably draw any conclusion from trials involving dystrophin-deficient dogs, which reproduce the complexity of the human disease.

Revisión histórica de la fisiología de las glándulas paratiroides / Historical review of the physiology of parathyroid glands

Las glándulas paratiroides fueron identificadas por primera vez en humanos, por Ivan Sãndstrom (1880). Von Recklinghausen en 1891 describe un "linfonódulo marrón rojizo" bajo la tiroides de un paciente con fibrosis quística ósea. Ese mismo año Gley asocio la pérdida en la función de las paratiroides con la tetania. Vassale y Generali publicaron un trabajo en 1897 realizado tras tiroidectomías en perros y concluyen que una de las funciones de las paratiroides era la remoción de toxinas, concordando con la "teoría de detoxificación". G. Moussu (1898) clamó haber tratado satisfactoriamente a un paciente con tetania administrándole extracto acuoso de paratiroides equinas. En 1903 Askanazy establece que los tumores de la glándula tiroides u otras glándulas endocrinas y afecciones descalcificantes esqueléticas podrían relacionarse al describir el primer caso de asociación entre un tumor paratiroideo y la enfermedad de Von Recklinghausen. MacCallum y Voegtlin (1924), tras numerosos estudios, dedujeron que la paratiroides actuaba como moduladora del metabolismo del calcio. Collip (1925) confirmó el rol protagónico de las paratiroides en la regulación del calcio mediante experimentos basados en que la "paratirina" podía aliviar la tetania post-paratiroidectomía Barnicot en 1948 concluye que la hormona paratiroidea estimula la resorción osteoclásica de forma directa; ese nismo año, Jahan y Pitts demostraron que esta hormona incrementa la reabsorción renal tubular de calcio y magnesio. En 1973, Aurbach purifica cierta cantidad de hormona paratiroidea, caracterizándose su estructura proteica y molecular. La clonación de su receptor por Jüppner y Abou-Samra (1991) permitió estudiar con mayor énfasis sus acciones celulares.

Parathyroid glands were identified by the first time in human beings by Ivan Sãndstrom (1880). Von Recklinghausen in 1891 describes "lymph node reddish brown" low thyroid of patients with fibrosis cystic in bones. The same year Gley associated the loss in the function of the parathyroids with tetania. Vassale and Generali published a review in 1897 realized after thyroidectomies in dogs and they concluded that one of the parathyroid functions was the renoval of toxins, agreeing with "theory of detoxification". G. Moussu (1898) cried out to have treated satisfactorily a patient with tetania administering watery extract of equine parathyroids. In 1903 Askanazy establishes that the tumors of the thyroid gland or other endocrines glands and decalcifying affections of the skeleton might be related on having described the first case of association between a parathyroid tumor and Von Recklinghausen's disease. Mac callum and Voegtlin (1924), alter numerous studies, deduced that parathyroid was actuating like modulating of the metabolism of the calcium. Collip (1925) confirmed the leading role of the parathyroid glands in the regulation of calcium by means of experiments based on which the "parathyrina" could relieve the postparathyroidectomy tetania. Barnicot in 1948 concludes that the parathyroid hormone stimulates the osteoclastic resorption directly, the same year, Jahan and Pitts demonstrated that this hormone increases the renal tubular reabsorption of calcium and magnesium. In 1973, Aurbach purifies certain quatity of parathyroid hormone, its multifaceted and molecular structure being characterized. The cloning of its receptor for Jüppner and Abou-Samra(1991) allowed to study with bigger emphasis its cellular actions.

Spasmophilia comorbidity in fibromyalgia syndrome.

OBJECTIVES: To evaluate the role of spasmophilia (SP) in fibromyalgia syndrome (FM). METHODS: Three hundred and fourteen patients (280 F, 34 M) with a diagnosis of FM or FM and spasmophilia (FM+SP) were recruited. Clinical assessment of patients and controls included the Questionnaires FIQ, HAQ and the tender point (TP) count. Life-time or ongoing psychiatric aspects were evaluated by trained psychiatrists by means of the classic scales: Structured Clinical Interview (SCID) for DSM-IV. The following analysis were evaluated: cytokine (IL1, IL2, IL6, IL8, IL10), TNF-α, cortisol, GH, ACTH, IGF1, 5HT, intracellular Mg, plasma calcium p(Ca), PTH, (25(OH)D) and thyroid functionality. Some typical symptoms were investigated. RESULTS: Eighty-one patients resulted positive for spamophilia (FM+SP), while 233 resulted negative for spasmophilia (FM). The mean TP number resulted higher in the FM group (15.33±3.88) with respect to FM+SP (12.88±6.17, p=0.016), while FIQ and HAQ did not differ between the two studied groups. FM patients exhibited a higher frequency of psychiatric disorders with respect to FM+SP patients (72% FM vs. 49% FM+SP, p<0.01). In particular the frequency of depression was 65.5% FM vs. 35% FM+SP (p<0.01). CONCLUSIONS: The presence of spasmophilia seems to influence psychiatric comorbidity which was less prevalent in FM+SP patients. FM is indeed characterised by an abnormal sensory processing of pain that seems to result from a combination of interactions between neurotransmitters, stress, hormones and the nervous system; spasmophilia would seem to be more linked to a dysfunction at the neuromuscular level.

Post-tetanic potentiation is caused by two signalling mechanisms affecting quantal size and quantal content.

A high-frequency action potential train induces post-tetanic potentiation (PTP) of transmission at many synapses by increasing the intra-terminal calcium concentration, which may increase the quantal content by activation of protein kinase C (PKC). A recent study found that an increase of the mEPSC size, caused by compound vesicle fusion, parallels PTP, suggesting that the quantal size increase also contributes to the PTP generation. However, the strength of this suggestion is somewhat undermined by recent studies suggesting that vesicles responsible for spontaneous and evoked EPSCs may originate from different pools. Furthermore, it is unclear whether the quantal size increase is also mediated by PKC. The present work addressed these issues at a large calyx of Held synapse. We found that PTP was caused by both a PKC-dependent increase of the quantal content and a PKC-independent increase of the quantal size. In addition, we found that mEPSCs and EPSCs were subjected to similar up- and down-regulation, which verifies the basic assumption of quantal analysis--the same mechanism controls the quantal size of spontaneous and evoked release. This verification supports the use of quantal analysis at central synapses. However, unlike the traditional quantal analysis that attributes the quantal size change to a postsynaptic mechanism, the present work, together with one of our previous studies, suggests that the quantal size increase is caused by a presynaptic mechanism, the compound fusion among vesicles that forms large compound vesicles.

GABAA receptor-mediated modulation of neuronal activity propagation upon tetanic stimulation in rat hippocampal slices.

Tetanic stimulation (100 Hz), which can induce long-term potentiation in synaptic connections in the hippocampal CA1 region, causes γ-aminobutyric acid (GABA)(A) receptor-mediated long-lasting depolarization of postsynaptic neurons. However, it is not clear how this stimulation modulates neuronal activity propagation. We studied tetanic burst-induced neuronal responses in the hippocampal CA1 region by using optical-recording methods employing a voltage-sensitive dye and focused on GABA(A) receptor-mediated modulation. We observed that burst stimulation induced long-lasting depolarization and progressive decrease in individual excitatory postsynaptic potentials (EPSPs). Both these effects were suppressed by picrotoxin, a GABA(A) receptor antagonist. Under whole-cell voltage-clamp conditions, we observed a long-lasting inhibitory current (IPSC) and a prominent progressive decrease in the amplitude of the excitatory postsynaptic current (EPSC). Further, picrotoxin inhibited the IPSC and the progressive decrease in EPSC. The optically recorded long-lasting depolarization and progressive decrease of EPSPs were strongly dependent on the distance between the recording electrode and the stimulation site. Optical recordings performed across a wide swatch of CA1 revealed that the decrease in activity propagation was followed by facilitation of propagation after recovery and that this facilitation also depended on GABA(A) receptors. Intense activation of GABA(A) receptors is a key factor shaping the spatiotemporal patterns of high-frequency stimulation-induced responses in the CA1 region.

Synergetic analgesia of propentofylline and electroacupuncture by interrupting spinal glial function in rats.

Previous studies indicated that disruption of glial function in the spinal cord enhanced electroacupuncture (EA) analgesia in arthritic rats, suggesting glia is involved in processing EA analgesia. To probe into the potential value for clinical practice, the present study was to investigate the effect of propentofylline, a glia inhibitor, on EA analgesia in rats. Mechanical allodynia induced by tetanic stimulation of sciatic nerve (TSS) was used as a pain model. On day 7 after TSS, EA treatment induced a significant increase in paw withdrawal threshold to mechanical stimulation. Intrathecal or intraperitoneal injection of propentofylline relieved TSS-induced mechanical allodynia. The combination of low dosage of propentofylline and EA produced more potent anti-allodynia than propentofylline or EA alone. Immunohistochemistry exhibited that TSS-induced activation of microglia and astrocytes was inhibited significantly by propentofylline. These results indicate that propentofylline and EA induce synergetic analgesia by interrupting spinal glial function.

A study of long-term potentiation in transgenic mice over-expressing mutant forms of both amyloid precursor protein and presenilin-1.

Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Abeta are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.

Overexpression of HSP10 in skeletal muscle of transgenic mice prevents the age-related fall in maximum tetanic force generation and muscle Cross-Sectional Area.

Skeletal muscle atrophy and weakness are major contributors to frailty and impact significantly on quality of life of older people. Muscle aging is characterized by a loss of maximum tetanic force (P(o)) generation, primarily due to muscle atrophy, to which mitochondrial dysfunction is hypothesized to contribute. We hypothesized that lifelong overexpression of the mitochondrial heat shock protein (HSP) HSP10 in muscle of mice would protect against development of these deficits. P(o) generation by extensor digitorum longus muscles of adult and old wild-type and HSP10-overexpressing mice was determined in situ. Muscles were subjected to damaging lengthening contractions, and force generation was remeasured at 3 h or 28 days to examine susceptibility to, and recovery from, damage, respectively. Muscles of old wild-type mice had a 23% deficit in P(o) generation and a 10% deficit in muscle cross-sectional area compared with muscles of adult wild-type mice. Overexpression of HSP10 prevented this age-related fall in P(o) generation and reduction in cross-sectional area observed in muscles of old wild-type mice. Additionally, overexpression of HSP10 protected against contraction-induced damage independent of age but did not improve recovery if damage occurred. Preservation of muscle force generation and CSA by HSP10 overexpression was associated with protection against the age-related accumulation of protein carbonyls. Data demonstrate that development of age-related muscle weakness may not be inevitable and show, for the first time, that lifelong overexpression of an HSP prevents the age-related loss of P(o) generation. These findings support the hypothesis that mitochondrial dysfunction is involved in the development of age-related muscle deficits.

Arteriolar vasomotor control and contractile performance during fatiguing tetanic contractions in rat skeletal muscle: role of sympathetic system.

Using a fatiguing stimulation protocol designed specifically to enhance sympathetically-mediated vasoconstrictor tone, we explored the temporal profile of the evoked vasoconstrictor response, evaluated the presence of sympatholysis, and assessed the role of alpha1-adrenergic receptor-mediated vasoconstriction on muscle performance. Spinotrapezius muscles of Wistar rats were exteriorized and stimulated tetanically (100 Hz, 4-7 V, stimulus duration 700 ms) every 3 s for 2.5 min under control and prazosin (1 muM) superfused conditions. The extent and time course of diameter changes in arterioles (2 A) and venules (2 V) were determined after each of 10 discrete sets of muscle stimulation at 5-min intervals. A significant decrease of luminal diameter was observed in arterioles after tetanic contractions at 8-10 sets (8 sets: -34.4%, 9 sets: -39.4%, 10 sets: -38.6% vs pre-contraction at each set, p < 0.01). Prazosin significantly reduced but did not abolish the contraction-induced vasoconstriction. In both conditions, there was no reduction of venules diameter observed. Tetanic contractions force at the final 10th set was significantly decreased to 29.3 +/- 11.9% from pre-fatigue conditions, while tetanic contractions with prazosin force production was maintained at 70.4 +/- 14.2% at the 10th set. We conclude that in sequential bouts of contractions there was a progressively greater degree of arteriolar (but not venular) vasoconstriction which was attenuated substantially by prazosin.

Acute passive stretching in a previously fatigued muscle: Electrical and mechanical response during tetanic stimulation.

The aim of this study was to assess the effects of acute passive stretching on the electrical and mechanical response of a previously fatigued muscle. Eleven participants underwent maximal tetanic stimulations (50 Hz) of the medial gastrocnemius, before and after a fatiguing protocol and after a bout of passive stretching of the fatigued muscle. During contraction, surface electromyography (EMG), mechanomyography (MMG), and force were recorded. The following parameters were calculated: (1) the EMG root mean square (RMS), mean frequency, and fibre conduction velocity; (2) MMG peak-to-peak and RMS; (3) the peak force, contraction time, half-relaxation time, peak rate of force development (dF/dt) and its acceleration (d(2)F/dt(2)). Fatigue reduced peak force by 18% (P < 0.05) and affected the other force, EMG, and MMG parameters. After stretching: (1) all EMG parameters recovered to pre-fatigue values; (2) MMG peak-to-peak remained depressed, while RMS recovered to pre-fatigue values; (3) the peak force, peak rate of force development and its acceleration were further reduced by 22, 18, and 51%, respectively, and half-relaxation time by 40% (P < 0.05). In conclusion, acute passive stretching, when applied to a previously fatigued muscle, further depresses the maximum force-generating capacity. Although stretching does not alter the electrical parameters of the fatigued muscle, it does affect the mechanical behaviour of the muscle-tendon unit.