Algogenic Peripheral Effects of RFa Peptides

Earlier, we showed on a nerve-skin preparation that FMRFa and other RFa-like peptides activate a considerable proportion of somatosensory nociceptive afferent units (C fibers). To check the algogenic effect of RFa peptides in vivo, we recorded the parameters of a few behavioral phenomena after subcutaneous injections of solutions of FMRFa and KNFLRFa into the hindlimb of mice. Introduction of the above peptides evoked intensive pain reactions of the animals manifested in long-lasting licking of the injected limb and an increase in the number of the cycles of licking of this limb. We hypothesize that interaction of RFa peptides with proton-activated ion channels (ASICs) in the membranes of sensory nociceptive neurons is one of the possible mechanisms of this nociceptive reaction. Neirofiziologiya/Neurophysiology, Vol. 37, No. 4, pp. 347–351, July–August, 2005.     

Activation of rat masticatory muscle afferent fibres by acidic pH

Abstract

Previous research findings have suggested an important role for acid sensing ion channels (ASICs) in muscle pain mechanisms. This study was conducted to determine if masticatory muscle afferent fibres express ASICs, if there are sex differences in this expression, and to compare the effects of low pH and hypertonic saline on afferent fibres that innervate the masticatory muscle in vivo. Immunohistochemistry methods were applied to examine the expression of ASICs in trigeminal ganglion neurons, while in vivo electrophysiology techniques were employed to examine changes in masticatory muscle afferent fibre excitability. Both ASIC₁ and ASIC₃ were expressed by predominantly larger masticatory muscle ganglion neurons, but the frequency of ASIC₃ expression (56%) was significantly greater than ASIC₁ (35%). No sex-related differences in expression were identified. Injection of pH 5.8, but not pH 6.8, phosphate buffered saline evoked afferent discharges that were significantly greater than those evoked by pH 7.4 buffer (control). Since ASIC₃ channels are not activated until the pH is around 6, these results indicate that activation of both channels contributes to excitation of masticatory muscle afferent fibres. The results further show that many masticatory muscle afferent fibres, which respond to low pH, are low threshold mechanoreceptors. These findings may explain why injection of low pH solutions into the masticatory muscles of healthy humans is not associated with significant muscle pain.     

Modulatory action of RFamide-related peptides on acid-sensing ionic channels is pH dependent: the role of arginine

Acid-sensing ionic channels (ASICs) are involved in such functions of the sensory nervous system as mechanoreception, nociception and perception of acid taste. Phe-Met-Arg-Phe amide-related (FMRFa-related) peptides in micro m concentrations slow down the rate of ASICs desensitization. Here we report that this effect is strongly pH dependent: the lower the pH used to activate ASICs, the larger is the modulatory effect of Arg-Phe amide-related (RFa-related) peptides. Pre-application of the peptides results in a change to the desensitization kinetics of the ASICs-operated current from monoexponential to biexponential: the fast component retains the control kinetics, whereas the slow one is induced by the peptide. The lower the pH, the larger is the slow component, whereas there is practically no modulation at pH 6.6. Phe-Met-Val-Phe amide (FMVFa), which has neutral valine instead of arginine, similarly modulates the kinetics of ASICs, but does not reveal pH dependence of this action. Thus, positively charged arginine regulates the access of the RFa-related peptides to the modulatory site. We suggest that the pH dependence of the modulatory action of RFa-related peptides can be associated with the interaction of a positively charged arginine with histidine residues in the molecule of ASIC.     

Suppression of abnormally increased excitability of monosynaptic spinal reflex arcs by riluzole

We studied the effects of a neuroprotector, riluzole, on the evoked mass activity of spinal neuronal mechanisms and on action potentials (APs) recorded from the sciatic nerve in intact rats and rats with the manifestations of postdenervational and 4-aminopyridine (4-AP)-induced hyperreflexia, as well as in animals in the superreflexia state (induced by combined action of denervation and 4-AP). We measured the parameters of monosynaptic reflex discharges (monosynaptic reflexes, MRs) recorded from the ventral root (VR), of the spinal dorsal surface potential (DSPs), and of mass APs evoked in afferent and efferent fibers of the SN before and 10, 30, 60, and 120 min after injection of riluzole. It was found that in intact animals riluzole significantly (by 60–70%) decreased the amplitude of VR MRs and those of the afferent peak and N₁ component of DSPs. Riluzole exerted smaller suppressive effects on mass APs in the afferent fibers of the SN; the effect on APs in the SN efferent fibers was the minimum (a 4 to 5% decrease). Under conditions of increased sensitivity of the motoneuronal postsynaptic membrane to the transmitter (postdenervational hyperreflexia) and an increased release of glutamate from presynaptic elements (4-AP-induced hyperreflexia), as well as under superreflexia conditions, the dynamics of suppression of the evoked spinal activity by riluzole showed relatively moderate differences from those in intact animals. Under the above conditions, riluzole in the same manner decreased the amplitude of VR MRs. In the superreflexia state, the agent blocked the development of additional components of these dramatically increased potentials (in the above state, their amplitude increased by nearly nine times, on average, and this resulted in the generation of such components). We believe that the inhibitory effect of riluzole on glutamatergic neurotransmission in the spinal cord is based, first of all, on blocking of excitation in afferent presynaptic terminals. The possibility to use riluzole for correction of abnormally increased hyperexcitability of the spinal neuronal systems is discussed. Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 416–423, September–December, 2005.     

电刺激大鼠巨细胞网状核对小脑浦肯野细胞自发和诱发电活动的影响

本研究在麻醉并制动的大鼠上观察了电刺激巨细胞网状核(Gi)对小脑浦肯野细胞(PC)自发及诱发简单锋电位的影响。结果如下:(1)刺激Gi可使PC的简单锋电位出现潜伏期小于20ms的抑制性或兴奋性反应,并以抑制性反应为主。抑制性反应持续40-100ms,而兴奋性反应的时程可达200ms以上;(2)注射5-HT_2型受体阻断剂methysergide可以减弱或阻断电刺激Gi对PC自发简单锋电位的抑制作用;(3)条件性Gi刺激可以显著压抑或加强由刺激对侧大脑皮层感觉运动区引起的PC诱发简单锋电位反应。以上结果说明:在大鼠存在Gi-小脑通路,这一通路中的部分纤维是5-HT能的。Gi-小脑纤维可能通过突触和/或非经典突触的化学传递方式对PC的电活动产生某种调制性的影响。推测Gi-小脑传入纤维投射可能在某些小脑功能活动,如肌紧张及姿势的调节等方面发挥重要作用。     

Effects of Stimulation of the Periaqueductal Gray and <Emphasis Type="Italic">Locus Coeruleus</Emphasis> on Postsynaptic Reactions of Cat Somatosensory Cortex Neurons Activated by Nociceptors

In cats, we studied the influences of stimulation of the periaqueductal gray (PAG) and locus coeruleus (LC) on postsynaptic processes evoked in neurons of the somatosensory cortex by stimulation of nociceptive (intensive stimulation of the tooth pulp) and non-nociceptive (moderate stimulations of the infraorbital nerve and ventroposteromedial nucleus of the thalamus) afferent inputs. Twelve cells activated exclusively by nociceptors and 16 cells activated by both nociceptive and non-nociceptive influences (hereafter, nociceptive and convergent neurons, respectively) were recorded intracellularly. In neurons of both groups, responses to nociceptive stimulation (of sufficient intensity) looked like an EPSP-spike-IPSP (the latter, of significant duration, up to 200 msec) complex. Electrical stimulation of the PAG (which could itself evoke activation of the cortical neurons under study) resulted in long-term suppression of synaptic responses evoked by excitation of nociceptors (inhibition reached its maximum at a test interval of 600 to 800 msec). We observed a certain parallelism between conditioning influences of PAG activation and effects of systemic injections of morphine. Isolated stimulation of LC by a short high-frequency train of stimuli evoked primary excitatory responses (complex EPSPs) in a part of the examined cortical neurons, while in other cells high-amplitude and long-lasting IPSP (up to 120 msec) were observed. Independently of the type of the primary response to PAG stimulation, the latter resulted in long-term (several seconds) suppression of the responses evoked in cortical cells by stimulation of the nociceptive inputs. The mechanisms of modulatory influences coming from opioidergic and noradrenergic brain systems to somatosensory cortex neurons activated due to excitation of high-threshold (nociceptive) afferent inputs are discussed.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 61–73, January–February, 2005.     

Inhibition by VIP and atriopeptin II on the field stimulation evoked release of [3H]noradrenaline in the rat portal vein.

The modulatory effects of vasodilatory peptides on noradrenaline release from sympathetic nerve terminals have been studied in the rat portal vein model. Transmural field stimulation of the longitudinally mounted vein preparation evoked concomitant increases in the [3H]noradrenaline overflow and the integrated tension. Both responses were abolished by guanethidine or tetrodotoxin, whereas only the tension response was blocked by phentolamine. CGRP and VIP, both being present in intramural nerve fibers in the rat portal vein, were compared with atriopeptin II for modulatory effects. CGRP (100 nM) had no effect on the overflow of [3H]noradrenaline or the integrated tension response to transmural stimulation. VIP (30 nM) and atriopeptin II (30 nM) both caused significant reductions of both [3H]noradrenaline overflow and the integrated tension. These results indicate that the decreased tension response to transmural stimulation in the presence of VIP or AP II reflects the sum of both pre- and postsynaptic inhibitions.     

Characterization and modeling of P-type electrosensory afferent responses to amplitude modulations in a wave-type electric fish

The first stage of information processing in the electrosensory system involves the encoding of local changes in transdermal potential into trains of action potentials in primary electrosensory afferent nerve fibers. To develop a quantitative model of this encoding process for P-type (probability-coding) afferent fibers in the weakly electric fish Apteronotus leptorhynchus, we recorded single unit activity from electrosensory afferent axons in the posterior branch of the anterior lateral line nerve and analyzed responses to electronically generated sinusoidal amplitude modulations of the local transdermal potential. Over a range of AM frequencies from 0.1 to 200 Hz, the modulation transfer function of P-type afferents is high-pass in character, with a gain that increases monotonically up to AM frequencies of 100 Hz where it begins to roll off, and a phase advance with a range of 15–60 degrees. Based on quantitative analysis of the observed gain and phase characteristics, we present a computationally efficient model of P-type afferent response dynamics which accurately characterizes changes in afferent firing rate in response to amplitude modulations of the fish's own electric organ discharge over a wide range of AM frequencies relevant to active electrolocation. Accepted: 14 June 1997     

Postsynaptic Reactions in Somatosensory Cortex Neurons Activated by Stimulation of Nociceptors: Modulation upon Stimulation of the Central Grey, <Emphasis Type="Italic">Locus Coeruleus</Emphasis>, and <Emphasis Type="Italic">Substantia Nigra</Emphasis>

In experiments on cats, we studied the effects of electrical stimulation of the cerebral central grey (CG), locus coeruleus (LC), and substantia nigra (SN) on postsynaptic processes evoked by nociceptive volleys in somatosensory cortex neurons. Nineteen cells activated exclusively by stimulation of nociceptors (intense stimulation of the dental pulp) and 26 cells activated by both nociceptive and non-nociceptive (near-threshold) stimulations of the n. infraorbitalis and thalamic nucl. ventroposteromedialis (VPM) were intracellularly recorded (nociceptive and convergent cortical neurons, respectively). In neurons of both groups, stimulation of both nociceptive afferents and the VPM evoked complex responses having on EPSP-spike-IPSP patterns (duration of IPSPs about 200-300 msec). Electrical stimulation of the СG, which per se could activate the examined cortical neurons, induced prolonged suppression of synaptic responses evoked by stimulation of nociceptors; maximum inhibition was observed at 600- to 800-msec-long conditioning–test intervals. A certain parallelism was observed between the conditioning effects of СG stimulation and effects of systemic introduction of morphine. Isolated stimulations of the LC and SN by short high-frequency pulse series evoked primary complex EPSPs in a part of the examined cortical neurons, while high-amplitude IPSPs (up to 120 msec long) were observed in other units. Independently of the type of the primary response, conditioning stimulations of the LC and SN induced long-lasting (several seconds) suppression of synaptic responses evoked in cortical neurons by stimulation of nociceptive inputs. Mechanisms of modulating influences coming from opioidergic, noradrenergic, and dopaminergic cerebral systems to neurons of the somatosensory cortex activated upon excitation of high-threshold (nociceptive) afferent inputs are discussed.     

Fatigue-induced modulation of the H reflex of soleus muscle in humans

We studied the effect of fatigue of the mm. gastrocnemius-soleus on the H reflex elicited by transcutaneous stimulation of n. tibialis and recorded from the m. soleus; healthy 18-to 34-year-old volunteers were tested. Fatigue was evoked by long-lasting (6 to 9 min) voluntary tonic static sole flexion of the foot (ankle extension) with a force equal to 75% of the maximum voluntary contraction (MVC). The amplitude of H reflex significantly (P < 0.001) decreased to about 60% of the initial value immediately after the period of fatiguing effort. Within 2 to 3 min, it relatively rapidly recovered and reached about 90% of the control, and this was followed by a period of slow recovery to about 96–97% of the initial value 30 min after conditioning fatigue. We suppose that the initial period of suppression of the H reflex results to a considerable extent in an increase in the intensity of presynaptic inhibition of transmission from Ia afferents due to tonic activation of high-threshold (groups III and IV) afferent fibers induced by intensive fatigue-related metabolic changes in the muscles. More long-lasting (tens of minutes) changes are related to slow reverse development of direct effects of fatigue-induced biochemical shifts in the muscle. Neirofiziologiya/Neurophysiology, Vol. 38, Nos. 5/6, pp. 426–431, September–December, 2006.     

Rapid aggregation and assembly in aqueous solution of A<Emphasis Type="Italic">β</Emphasis> (25–35) peptide

The highly toxic Aβ(25–35) is a peculiar peptide that differs from all the other commonly studied β-amyloid peptides because of its extremely rapid aggregation properties and enhanced neurotoxicity. We investigated Aβ(25–35) aggregation in H₂O at pH 3.0 and at pH 7.4 by means of in-solution analyses. Adopting UV spectroscopy, Congo red spectrophotometry and thioflavin T fluorimetry, we were able to quantify, in water, the very fast assembling time necessary for Aβ(25–35) to form stable insoluble aggregates and their ability to seed or not seed fibril growth. Our quantitative results, which confirm a very rapid assembly leading to stable insoluble aggregates of Aβ(25–35) only when incubated at pH 7.4, might be helpful for designing novel aggregation inhibitors and to shed light on the in vivo environment in which fibril formation takes place.     

Response of sensory receptors of the cat's hindlimb to a transient,step-function DC electric field

There are two possible mechanisms of effects of large electric fields on animals, one caused by the electric field at the body surface and the other caused by the electric current induced inside the body. The purpose of the present experiments was to investigate the former possibility by recording action potentials from afferent fibers innervating various sensory receptors in the cat's hindlimb. Cat hairs were attracted to the upper electrode when exposed to DC electric fields of 180 kV/m or greater, and action potentials were evoked in the afferent fibers innervating G₁, G₂, and down hair receptors. No action potentials were evoked in afferent fibers innervating type I, type II, field receptors, muscle spindles, or joint receptors. These results indicate that a strong DC electric field induced movement of the hairs, eventually evoked excitation of the hair receptors, but that other receptors located under the skin were not influenced by electric field exposure.     

Changes in antidromic discharges in peripheral nerves during polarization of the cat spinal cord by a steady current

The effect of a steady current passed through the spinal cord on antidromic discharges in primary afferent groups of Agb cutaneous nerves of the hind limb, evoked by single and paired stimulation of the terminals of these fibers, was investigated by Wall's technique in acute experiments on spinal and anesthetized cats. A current of up to 50–100 µA, flowing in the dorso-ventral direction, led to an increase in amplitude of antidromic dischanges evoked by single stimulation of afferent terminals; if the current flowed in the opposite direction, the opposite effect was observed. The relative degree of facilitation of antidromic discharges caused by conditioning stimulation of these same fibers was reduced by a polarizing current in either direction. It is suggested that the effects of the action of a steady current flowing through the spinal cord observed in these experiments are due mainly to shifts of membrane potential in primary afferent terminals.Dnepropetrovskii State University. Translated from Neirofiziologiya, Vol. 14, No. 4, pp. 386–391, July–August, 1982.     

Interaction of influences from the auditory and somatosensory afferent systems on neurons of the primary auditory cortex

In experiments on anesthetized cats, 80 neurons of the primary auditory cortex (A1) were studied. Within the examined neuronal population, 66 cells (or 82.5%) were monosensory units, i.e., they responded only to acoustic stimulations (sound clicks and tones); 8 (10.1%) neurons responded to acoustic stimulation and electrocutaneous stimulation (ECS); the rest of the units (7.4%) were either trisensory (responded also to visual stimulation) or responded only to non-acoustic stimulations. In the A1 area, neurons responding to ECS with rather short latencies (15.6–17.0 msec) were found. ECS usually suppressed the impulse neuronal responses evoked by sound clicks. It is concluded that somatosensory afferent signals cause predominantly an inhibitory effect on transmission of an acoustic afferent volley to the auditory cortex at a subcortical level; however, rare cases of excitatory convergence of acoustic and somatosensory inputs toA1 neurons were observed.     

Effects of Near-Threshold Stimulation of the Vestibular Apparatus on Postural Responses Evoked by Displacements of the Visualized Surrounding

In healthy subjects in the relaxed upward stance and perceiving a virtual visual environment (VVE), we recorded postural reactions to isolated visual and vestibular stimulations or their combinations. Lateral displacements of the visualized virtual scene were used as visual stimuli. The vestibular apparatus was stimulated by application of near-threshold galvanic current pulses to the proc. mastoidei of the temporal bones. Isolated VVE shifts evoked mild, nonetheless clear, body tilts readily distinguished in separate trials; at the same time, postural effects of isolated vestibular stimulation could be detected only after averaging of several trials synchronized with respect to the beginning of stimulation. Under conditions of simultaneous combined presentation of visual and vestibular stimuli, the direction of the resulting postural responses always corresponded to the direction of responses induced by VVE shifts. The contribution of an afferent volley from the vestibular organ depended on the coincidence/mismatch of the direction of motor response evoked by such a volley with the direction of response to visual stimulation. When both types of stimulations evoked unidirectional body tilts, postural responses were facilitated, and the resulting effect was greater than that of simple summation of the reactions to isolated actions of the above stimuli. In the case where isolated galvanic stimulation evoked a response opposite with respect to that induced by visual stimulation, the combined action of these stimuli of different modalities evoked postural responses identical in their magnitude, direction, and shape to those evoked by isolated visual stimulation. The above findings allow us to conclude that the effects of visual afferent input on the vertical posture under conditions of our experiments clearly dominate. In general, these results confirm the statement that neuronal structures involved in integrative processing of different afferent volleys preferably select certain type of afferentation carrying more significant or more detailed information on displacements (including oscillations) of the body in space.     

Raphe Stimulation-Evoked Modulation of Postsynaptic Responses by Neurons of the Cat Somatosensory Cortex Activated by Stimulation of Nociceptors

We studied the effects of electrical stimulation of the raphe nuclei (RN) of the cat brain on postsynaptic potentials developing in somatosensory cortex neurons activated by nociceptive influences. Intracellular records were obtained from 15 cells, which were either selectively excited by stimulation of nociceptors (intense electrical stimulation of the dental pulp) or activated by both the above nociceptive and non-nociceptive (moderate stimulations of the infraorbital nerve or thalamic ventroposteromedial nucleus, VPMN) influences. In neurons of both groups, stimulation of both nociceptive afferents and the VPMN evoked complex responses (EPSP–AP–IPSP; IPSPs were 200 to 300 msec long). In some studied cortical neurons, isolated electrical stimulation of the RN (which caused the release of serotonin, 5-HT, in the cortex) resulted in relatively short-latency synaptic excitation, while inhibition was observed in other cells. In the case where stimulation of the RN was used as conditioning influence, such stimulation (independently of the kind of the initial response to RN stimulation) led to long-latency and long-lasting suppression of all components of the synaptic reactions evoked by excitation of nociceptors. The maximum of inhibition was observed at test intervals of 300 to 800 msec. The mechanisms underlying modulatory influences coming from the 5-HT-ergic brainstem system to neurons of the somatosensory cortex, which are activated by excitation of high-threshold (nociceptive) afferent inputs, are discussed.     

Role of Acetylcholine in the Modulation of Activity of Neocortical Neurons in Awake Animals Performing an Instrumental Conditioned Reflex

We studied modulatory effects of the cholinergic system on the activity of sensorimotor cortex neurons related to realization of an instrumental conditioned placing reflex. Experiments were carried out on awake cats; multibarrel glass microelectrodes were used for extracellular recording of impulse activity of neurons in the sensorimotor cortex and iontophoretic application of synaptically active agents within the recording region. The background and reflex-related activity was recorded in the course of realization of conditioned movements, and then changes of spiking induced by applications of the testing substances were examined. Applications of acetylcholine and carbachol resulted in increases in the intensity of impulse reactions of neocortical neurons evoked by presentation of an acoustic signal and in simultaneous shortening of the response latencies. An agonist of muscarinic receptors, pylocarpine, exerted a similar effect on the evoked activity of sensorimotor cortex neurons. Blockers of muscarinic receptors, atropine and scopolamine, vice versa, sharply suppressed impulse reactions of cortical neurons to afferent stimulation and simultaneously increased latencies of these responses. Applications of an agonist of nicotinic receptors, nicotine, was accompanied by suppression of impulse neuronal responses, an increase in the latency of spike reactions to presentation of a sound signal, and a corresponding increase in the latency of a conditioned motor reaction. In contrast, application of an antagonist of nicotinic receptors, tubocurarine, significantly intensified neuronal spike responses and shortened their latency. The mechanisms underlying the effects of antagonists of membrane muscarinic and nicotinic cholinoreceptors and the role of activation of these receptors in the modulation of activity of pyramidal and non-pyramidal neocortical neurons related to realization of the instrumental motor reflex are discussed.     

Facilitation and Inhibition of the <Emphasis Type="Italic">Soleus</Emphasis> H Reflex Related to Movements of the Upper Limb in Humans

In studies on healthy volunteers, we recorded an EMG discharge from the m. soleus corresponding to the H reflex evoked by transcutaneous stimulation of the n. tibialis comm. Changes in the magnitude of this reflex related to realization of brief voluntary movements of the ipsilateral upper limb were examined. The subjects were in a prone position. Fast flexion-extension of the forearm resulted first in 100- to 200-msec-long facilitation of the H reflex begun 30–40 msec before the appearance of EMG activity in the m. biceps brachii; this feature is indicative of the central nature of this effect related to the action of motor programs initiating the forearm movement. Facilitation of the H reflex was followed by its inhibition lasting several seconds. Within an interval corresponding to the maximum suppression of the H response, we tested the effect of additional conditioning stimulation of the n. peroneus comm. Occlusion of the inhibitory effects indicates that the same inhibitory neurons mediate the influences from both the peroneal input and the pathways transmitting inhibitory influences from the neuronal systems controlling upper limb muscles. Contractions of the ipsilateral m. biceps brachii evoked by direct electrical stimulation of the latter also resulted in inhibition of the soleus H reflex, which was rather similar in its time course to the above-mentioned inhibitory effects. There was no inhibition of the reflex after stimulations of the cutaneous receptors and n. medianus. These findings allow us to suppose that long-lasting inhibition of the H reflex induced by voluntary movements of the upper limb results from afferent influences from the receptors of contracting muscles. Such effects can be realized via the propriospinal pathways or long reflex arcs.     

Pain and neurotransmitters

1. To study physiological roles of substance P (SP), gamma-aminobutyric acid (GABA), enkephalins and other endogenous substances, we developed several kinds of isolated spinal cord preparations of newborn rats. 2. In these preparations, various slow responses of spinal neurons evoked by stimulation of primary afferent C fibers were depressed by a tachykinin antagonist, spantide. These results together with many other lines of evidence suggest that SP and neurokinin A serve as pain transmitters in a subpopulation of primary afferent C fibers. 3. Some C-fiber responses in various isolated spinal cord preparations were depressed by GABA, muscimol, and opioid peptides. In contrast, bicuculline (GABA antagonist) and naloxone (opioid antagonist) potentiated the "tail pinch potential," i.e., a nociceptive response of the ventral root evoked by pinch stimulation of the tail in isolated spinal cord-tail preparation of the newborn rat. The latter results support the hypothesis that some primary afferents activate inhibitory spinal interneurons which release GABA and enkephalins as transmitters to modulate pain inputs.     

Reflex cardiovascular responses evoked by selective activation of skeletal muscle ergoreceptors

It is well known that theexercise pressor reflex (EPR) is mediated by group III and IV skeletalmuscle afferent fibers, which exhibit unique discharge responses tomechanical and chemical stimuli. Based on the difference in dischargepatterns of group III and IV muscle afferents, we hypothesized thatactivation of mechanically sensitive (MS) fibers would evoke adifferent pattern of cardiovascular responses compared with activationof both MS and chemosensitive (CS) fibers. Experiments were conductedin chloralose-urethane-anesthetized cats (n = 10).Passive muscle stretch was used to activate MS afferents, andelectrically evoked contraction of the triceps surae was used toactivate both MS and CS muscle afferents. No significant differenceswere shown in reflex heart rate and mean arterial pressure (MAP)responses between passive muscle stretch and evoked muscle contraction. However, when the reflex responses were matched according totension-time index (TTI), the peak MAP response (67 ± 4 vs.56 ± 4 mmHg, P < 0.05) was significantly greaterat higher TTI (427 ± 18 vs. 304 ± 13 kg · s, highvs. low TTI, P < 0.05), despite different modes ofafferent fiber activation. When the same mode of afferent fiberactivation was compared, the peak MAP response (65 ± 7 vs. 55 ± 5 mmHg, P < 0.05) was again predicted bythe magnitude of TTI (422 ± 24 vs. 298 ± 19 kg · s,high vs. low TTI, P < 0.05). Total sensory input fromskeletal muscle ergoreceptors, as predicted by TTI and not the modalityof afferent fiber activation (muscle contraction vs. passive stretch),is suggested to be the primary determinant of the magnitude of theEPR-evoked cardiovascular response.