Sympathetic reflex responses presumably specific for nociceptive stimulation

1. In superficially anaesthetized and in unanaesthetized decerebrate cats, tetanic stimulation of A or A + C afferent fibres of the tibial nerve evoked in renal and inferior cardiac nerves a three-phasic change of activity, which consisted of a short powerful burst of discharges, followed by an inhibitory pause and then, by a moderate excitation. When such a command appeared in sympathetic nerves, reflex rising of systemic arterial pressure was extremely fast. 2. The latencies of the three-phasic command and of the so-called very late A response are almost the same. The very late A response is evident if the central nervous system is in the same state as when repetitive stimulation of A afferents evokes the three phasic command in sympathetic nerves and a steep rise of systemic arterial pressure. This permits the assumption that the very late A response reflects the excitation of just those central structures that on repetitive stimulation organize the three-phasic command. 3. A command of this kind is shown to ensure the optimal-time-control of the heart and blood vessels. Such a control (three-phasic command) is supposed to be evoked by nociceptive stimulation, i.e., to be specific for the defence reaction.     

Recovery of the human compound action potential following prior stimulation

The recovery from prior stimulation of the compound action potential (CAP) was measured using a forward masking stimulus paradigm in four normal-hearing, human subjects. The CAP was recorded using a wick electrode placed on the tympanic membrane. The effects of a 4000-Hz, 97-dB SPL conditioning stimulus on CAP amplitude in response to a 4000-Hz probe were measured as a function of conditioner-probe interval for three probe levels. The normalized probe response amplitude was completely recovered to the control values at an average conditioner-probe interval of 1359 ms, similar to that observed in chinchilla (Relkin, E.M., Doucet, J.R., Sterns, A., 1995. Recovery of the compound action potential following prior stimulation: evidence for a slow component that reflects recovery of low spontaneous-rate auditory neurons, Hear. Res. 83, 183-189). The present results are interpreted as a consequence of the slow recovery of low spontaneous-rate (SR), high threshold neurons from prior stimulation (Relkin, E.M., Doucet, J.R., 1991. Recovery from prior stimulation. I: Relationship to spontaneous firing rates of primary auditory neurons. Hear. Res. 55, 215-222) and may provide indirect physiological evidence for the existence of a class of low-SR auditory neurons in humans.     

Experimental muscle pain increases the human stretch reflex

In this study we investigated the effect of human experimental muscle pain on H- and stretch reflexes as indicators of changes in muscle spindle sensitivity. Fourteen healthy, male volunteers participated in the study. Muscle pain was produced by infusion of 5% hypertonic saline over a period of 10-15 min in m. soleus and in m. tibialis anterior. Reflexes were elicited in the relaxed and active soleus muscle (10-15 Nm ankle torque) before, during and after muscle pain. Control measurements were made with infusions of 0.9% isotonic saline. Surface electromyograms (EMG) were measured from the soleus muscle, and torque was measured from the ankle joint. With pain in the soleus muscle the mechanical stretch reflex response (ankle torque) increased significantly (P = 0.0007) as compared to before pain. With pain in the tibialis anterior muscle both the mechanical and EMG responses increased significantly (P = 0.001; P = 0.0003) as compared to before pain. The H-reflex showed no significant changes during the infusions in either muscles. This study has demonstrated a muscle pain-related increase in the amplitude of the stretch reflex without a corresponding increase in the H-reflex amplitude. One explanation could be an increased dynamic sensitivity of the muscle spindles during muscle pain caused by an increased firing rate in the dynamic gamma-motoneurones. However, the data could not support the vicious cycle model because the excitability of the alpha-motoneurone pool was unchanged.     

Morphological responses and molecular modifications in tomato plants after mechanical stimulation

Study of the growth responses of Lycopersicon esculentum (Mill. cv. VFN8) to mechanical stimulation applied to a single young internode showed a rapid and sharp decrease in stem elongation and an inhibition of elongation of several internodes, indicative of information transmission in the plant. A new tomato cDNA partial clone encoding calmodulin was isolated and used to study the time course of the gene induction in response to the rubbing treatment. Northern blot analysis showed a maximum accumulation of calmodulin mRNA 2 h after mechanical stimulation, not only in the rubbed internode, but also in upper and lower internodes and in young leaves. Treatment of the plant with calcium and EGTA showed the involvement of calcium and, in particular, intracellular calcium in calmodulin gene expression and cellular response.     

Neuropeptide Y-mediated pressor responses following high-frequency stimulation of the rat sympathetic nervous system

Recombinations between c-myc and immunoglobulin (Ig) sequences that typically occur in pristane-induced mouse plasmacytomas were detected in secondary lymphoid tissues from normal mice, chiefly in the gut-associated lymphoid tissue. Based on the analysis of recombination sequences as clonotypic markers, migration of c-myc recombination-positive cells was observed between Peyer's patches and into the intestine. Treatment of plasmacytoma-susceptible BALB/cAn mice with pristane induced proliferation and migration of these cells into mesenteric lymph node, spleen, and oil granuloma within 7 days. Plasmacytoma-resistant strains of mice (DBA/2N, C3H/HeJ, C57BL/6) differed in that (1) they harbored fewer clones (Ig/c-myc recombinations were detected in 33% of resistant mice versus 91% of BALB/cAn mice after pristane treatment); (2) Ig/c-myc-positive cells were rarely detected in the oil granuloma, and (3) c-myc recombined predominantly with the Ig alpha locus in BALB/cAn mice (72%), but with the Ig mu locus in DBA/2N and in C57BL/6 (67%). The results demonstrate that normal mice generate a large number of lymphocytes with aberrant c-myc in intestinal tissues without developing tumors.     

Interaction between muscle stiffness and stretch reflex sensitivity after long-term stretch-shortening cycle exercise

The short latency stretch-reflex component (M1) and its interactions with muscle stiffness and with muscle performance were investigated before and after long-term stretch-shortening cycle (SSC) exercise. Dramatic fatigue induced reduction in maximal SSC performance capability, and electromyographic activity was accompanied by a consistent decrease in the M1 reflex component and eccentric peak stiffness of the muscle. It can be suggested, therefore, that the decreased muscle performance is not simply a direct effect of central or peripheral fatigue, but is partly due to impairment of the ability to utilize stiffness-related elastic energy.     

Effects of dorsolateral spinal lesions on stretch reflex threshold and stiffness in awake cats

Measurements of threshold angle and incremental dynamic stiffness (IDS) were derived from triceps surae stretch reflexes, elicited by ramp and hold flexion at the ankle joint of four cats that were tested while awake. Stretch reflexes were assessed from trials that began from different ankle joint start positions or were matched using a post-hoc analysis for initial background force during testing sessions before and following unilateral lesions of the dorsolateral funiculus at levels ranging from T13 to L3. Unilateral lesions of the dorsolateral funiculus (DLF) produced significant ipsilateral decreases in stretch reflex threshold and increases in reflex gain, measured as incremental dynamic stiffness (IDS). ANCOVA testing indicated that the reduction in threshold, but not the increase in IDS, was dependent upon the level of background force. Reflex testing from different start angles demonstrated that DLF lesions diminished the correlation between threshold and IDS. Intravenous infusion of ketamine dose-dependently reduced IDS, compared with testing in the unanaesthetized state. Postoperative reflex testing during infusion of ketamine at 22.2 mg/kg per h, when electromyographic responses were reduced to 24% of control levels, abolished differences in IDS between the ipsilateral and contralateral hindlimbs. These and related observations suggest that the postoperative increase in IDS in awake animals was not due to an increase in passive stiffness.     

The stretch reflex in the Eaton Lambert syndrome, myasthenia gravis and myotonic dystrophy

The stretch reflex at rest and after muscle work was studied in three cases of Eaton Lambert syndrome. After muscle work a potentiation of the stretch reflex was demonstrated clinically and electrophysiologically. The presence of muscle stretch reflexes and their potentiation after muscle work was correlated with the clinical stage of the disease. The enhancement of the stretch reflex after voluntary effort was absent in normal subjects, myasthenia gravis and myotonic dystrophy.     

Modulation of the mandibular stretch reflex sensitivity during various phases of rhythmic open-close movements in humans

Enzymatically formed peptides show positional variations as well as highly conserved amino acids. In the cases of gramicidin S, tyrocidine, linear gramicidins, enniatins, echinocandins and viridogrisein in vivo and in vitro studies indicate substrate selection at the level of amino acid activation as a major control step. Evidence for proof-reading steps beyond activation has been obtained in penicillin and cyclosporin biosynthesis. Activated substrate analogues may promote the formation of side products such as dipeptides and cyclodipeptides. Modifications of intermediates, such as N-methylation, influence the rates of peptide synthesis. These control steps pose limitations for the application of such enzyme systems in the production of peptide libraries. They may originate from a target oriented evolution of these synthetases.     

Responses of ligamentous fibroblasts to mechanical stimulation

Mechanical stimulation, as provided by physiotherapy or controlled motion is essentially the only factor able to improve anterior cruciate ligament (ACL) healing. We investigate the cellular effects of such stimulus. Two types of stimulations are applied on canine ACL fibroblasts: repetitive stretch of an elastomeric adhesion substrate and a laminar flow of culture media over the culture surface. Cell orientation, proliferation rate, synthesis and type of collagen as well as proteoglycans (PG) synthesis and hydrodynamic characteristics have been studied. According to our results, the fibroblasts tend to align perpendicularly to the deformation axis of their substrate, and along a laminar flow. The shear stress induced by the laminar flow does not modify significantly proliferation rate nor extracellular matrix synthesis. Substrate stretching however, increases proliferation rate, collagen synthesis, mostly type III, and PG synthesis, principally of small sizes. The characteristics of fibroblasts submitted to repeated deformation match those of fibroblasts from ligament scar tissues. Their orientation perpendicular to substratum deformation differs from the one usually encountered in the undamaged tissue: aligned on the ligament axis.     

Spinal reflex pattern to foot nociceptive stimulation in standing humans

We describe here the results of a screening program conducted to discover inhibitors of the type-I interleukin-1 receptor (IL-1RI) from samples of microbial origin. An innovative approach, based on automated, nonradioactive receptor binding assays has been employed. Specially prepared cell-free systems have allowed the use of high concentrations of microbial metabolites in the reaction mixtures with a low percentage of false positives. More than 30,000 microbial samples from different species of soil isolates have been tested and two interesting activities have been purified and characterized. One of these, isolated from Streptomyces sp. GE48009, was identified as niphimycin, an antifungal agent also known as scopafungin. Preliminary evidence suggests that this molecule and azalomycin F, a structural analogue, inhibit IL-IRI by virtue of their long-chain guanidinium moiety. The other activity, isolated from Aspergillus sp. GE49752, was identified as flavipin, a substituted o-phthalaldehyde.     

Changes in reflex excitability following isometric contraction in humans

The dose rate at which cells are exposed to X-rays may influence the nature of induced mutations. To investigate this, the molecular spectra were determined at the HPRT gene in a hamster (V79) and a human (WI-L2-NS) cell line after the same total dose of X-rays has been administered at either a low dose rate (LDR; 3.33 mGy/min) or a high dose rate (HDR; 1.24-1.4 Gy/min) X-irradiation. Mutational spectra appeared similar, the fraction of mutants carrying deletions ranging between 59%-66% for the V79 strain and between 64%-75% for the WI-L2-NS strain, and independent of the irradiation conditions. The data indicate no effect of ongoing repair processes under LDR conditions on the kind of induced mutations in mammalian cells.     

Reversal of fusimotor reflex responses during locomotion in the decerebrate cat

The effect of brief trains of electrical stimulation, at 2, 3 and 20 x threshold (T), of cutaneous afferents in the medial plantar nerve on the discharges of single medial gastrocnemius static and dynamic gamma-efferents has been investigated at rest and during locomotion in a decerebrate cat preparation. The units were classified as dynamic (10 units) or static (10 units) indirectly on the basis of their resting and locomotor discharge characteristics. Responses were assessed by calculating the change in mean gamma-rate during the 100 ms after stimulus onset compared with a control period. At rest, most dynamic neurones were inhibited by stimulation at 2T (9 of 10 units) and above. In contrast, the resting responses of most static neurones were excitatory at 2T (9 of 10 units) and 3T, while 20T produced static gamma-effects that varied in sign. During locomotion the responses of both types of gamma-efferent were phase related. Two patterns were observed with dynamic units. For seven dynamic neurones, at stimulus levels of 2T (7 units) and above, responses during electromyogram (EMG) bursts were inhibitory while those between bursts were not significantly different from zero. However, for three other dynamic units, a phase-related reversal of reflex responses was observed at some stimulus intensities (always 2T, 3 units) comprising inhibition during, and excitation between, EMG bursts. For static neurones, inhibitory (never excitatory) responses occurred during walking at stimulus intensities of 2T (10 units) and above. The locomotor responses of static units were maximum during (3 units) or between (7 units) EMG bursts and were minimum in the opposite phase of EMG activity. A task-related reversal of reflex responses was thus generally apparent (9 of 10 units) to low intensity stimulation (2T) for static gamma-efferents during locomotion (inhibition) compared with rest (excitation). During locomotion there was a significant linear relation between the magnitude of response and the background gamma-rate for static units and those dynamic units that did not exhibit phase-related reflex reversal (total, 17 units). For dynamic gamma-efferents, inhibition at rest and during locomotion occurred at short (spinal) latencies which were not significantly different and are consistent with the involvement of the same interneuronal pathway. We conclude that pathways of opposite sign may dominate the responses of fusimotor neurones to low threshold cutaneous afferents from the plantar surface of the foot depending on behavioural context. Furthermore, the cutaneous reflex responses of both types of gamma-motoneurones during locomotion appear to vary with the source of the afferent input and do not constitute a general excitatory drive. The results are discussed in relation to the role and reflex control of the fusimotor system.     

Melanin biosynthesis patterns following hormonal stimulation

The effect of melanocyte-stimulating hormone (MSH) on the differentiation of mammalian melanocytes has been widely studied since the early 1950s. There have been many reports about the stimulatory effect of MSH on melanin production and specifically on the activity of tyrosinase, the critical enzyme in the melanogenic pathway. However, few and variable results have been obtained concerning the effect of this hormone on the regulation of DOPAchrome tautomerase (TRP2), another melanogenic enzyme which functions later in the melanogenic pathway, or on other melanogenic activities, such as TRP1. In this study, we show that the MSH-induced stimulation of tyrosinase is accompanied by no significant change in the synthesis or catalytic activities of other melanogenic enzymes such as TRP1 or TRP2. This in turn elicits a dramatic increase in melanin production accompanied by a significant decrease in the incorporation of carboxylated precursors into that melanin biopolymer, although the biological implication of that is still unclear.     

Mechanism of coronary microvascular responses to metabolic stimulation

Previous studies from our laboratory have shown that coronary microvascular dilation to increased myocardial oxygen consumption (MVO2) is greater in vessels < 100 microns. The mechanism responsible for this response is uncertain. OBJECTIVES: We tested the hypothesis that microvascular dilation to increased MVO2 is mediated by nitric oxide (NO). Since NO release may occur in response to increased shear, we also tested the hypothesis that metabolic byproducts released in response to increase in MVO2 will stimulate opening of the ATP-sensitive potassium channel. METHODS: Changes in epicardial coronary microvascular diameters were measured in 9 dogs given NG-nitro-L-arginine (LNNA; 100 microM, topically), 7 dogs given glibenclamide (10 microM, topically) and 12 control (C) dogs during increases in metabolic demand using dobutamine (DOB, 10 micrograms/kg/min, i.v.) with rapid atrial pacing (PAC, 300 bpm). Diameters of arterioles were measured using intravital microscopy coupled to stroboscopic epi-illumination. RESULTS: During the protocol, MVO2 increased to a similar degree in both experimental groups (LNNA and glibenclamide). Baseline hemodynamics and coronary microvascular diameters were similar between the two experimental groups and their respective control groups. In the presence of LNNA, coronary arteriolar (< 100 microns) dilation (% change from baseline) was impaired during the protocol (DOB: vehicle 18 +/- 5, LNNA 2 +/- 2 [P < 0.05]; DOB + RAP: vehicle 40 +/- 11, LNNA 6 +/- 2% [P < 0.05]). In contrast, glibenclamide did not impair coronary microvascular responses to increased MVO2 despite increases in MVO2. CONCLUSION: This study indicates that coronary microvascular dilation in response to increased metabolic stimulation using dobutamine in conjunction with rapid pacing is mediated through a nitric-oxide-dependent mechanism and not ATP-sensitive potassium channels. These results may have important implications in pathological disease states where nitric oxide mechanisms are impaired, such as diabetes and hypertension.