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S Mense

Publications and source records attributed to S Mense.

85 records · Page 5Linked to original sources

Sensitization of group IV muscle receptors to bradykinin by 5-hydroxytryptamine and prostaglandin E2.

The aim of the study was to find out whether endogenous substances with a presumed sensitizing action on nociceptors alter the chemical excitability of muscle receptors with unmyelinated afferent fibres. In anaesthetized cats, the discharges of single group IV units in response to intra-arterial injections of bradykinin were evaluated quantitatively and the influence of 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) on the response magnitude determined. Both 5-HT and PGE2 enhanced the bradykinin sensitivity of most of the muscle receptors, i.e. the receptors were sensitized to bradykinin by 5-HT and PGE2. Units that were activated by bradykinin before administration of the sensitizing chemicals showed an increase in response magnitude; in receptors not responding to the standard dose of bradykinin an activation often occurred after chemical sensitization. It is occurred that under the influence of elevated tissue levels of 5-HT and PGE2 the afferent impulse activity induced in group IV muscle receptors by bradykinin will be higher. As the substances used are released together from pathologically altered organs and since many of the group IV muscle receptors are considered to be nociceptive, the chemical sensitization of these receptors to the algesic agent bradykinin might play a role in the production of pain in an inflamed or injured muscle.

Animals↗

Muscle receptors with fine afferent fibers which may evoke circulatory reflexes.

The majority of afferent nerve fibers in mammalian skeletal muscle are thin myelinated (A delta or group III) and unmyelinated (C or group IV) afferents. Some 50% of these units appear to be responsible for the reception of noxious chemical, mechanical, and thermal stimuli, i.e., they are nociceptors. The other receptive units with fine afferent fibers presumably are activated by moderate innocuous stimuli such as light stretch, contractions, and light local touching. They possibly play a role in the circulatory and respiratory adjustments during exercise, i.e. they may be ergoreceptors. The data presently available suggest that the nociceptive as well as the ergoreceptive units are very heterogeneous groups with diverse receptive properties. The sensitivity of an individual unit may be restricted to the mechanical domain or to a single chemical substance, whereas other receptors respond to a great variety of chemical, mechanical, and probably thermal stimuli. Each receptor, however, seems to have a preferred susceptibility or "dominant sensitivity" to one or the other stimulus. This sensitivity may be modified by various factors, such as the local concentration of prostaglandins or serotonin. The concept of different types of fine afferent units is supported by preliminary ultrastructural findings showing a great structural diversity both in regard to the localization and the structural design of the receptive endings of these afferents.

Animals↗

Descending influences on the responses of spinocervical tract neurones to chemical stimulation of fine muscle afferents.

1. In cats, extracellular micro-electrode recordings were made from axons of the spinocervical tract (s.c.t.) in both the decerebrate state and during cold block of the spinal cord (reversible spinal state) to examine the effects of intra-arterial injection of algesic agents (bradykinin, potassium, 5-hydroxytryptamine) into the gastrocnemius-soleus (g.s.) muscle on the discharge behaviour of s.c.t. neurones.2. In the decerebrate state without cooling the spinal cord 13% of the cells (eleven out of eighty-three) responded to intra-arterial injection of bradykinin, 33% (twenty-two out of sixty-nine) to 5-hydroxytryptamine, and 38% (thirty-five out of ninety-one) to potassium injection.3. The general time course and the latency of the responses of s.c.t. cells induced by injection of pain-producing substances into the g.s. muscle reflect in many respects the activations of g.s. group III and group IV primary afferent units studied previously.4. For twenty-seven s.c.t. neurones the period of recording was long enough to record the responses of the same cell to injections of algesic agents in both the decerebrate and the reversible spinal state. In the reversible spinal state 83% (nineteen out of twenty-three) of the s.c.t. neurones tested with all the three substances responded to at least one of the algesic agents. In the decerebrate state the percentage was lower (39%).5. Reversible spinalization led not only to a significant increase in the number of s.c.t. neurones responding to the algesic agents used but also to an increase in the magnitude of the chemically induced responses.6. The mean latency of the responses of neurones that were activated in both preparations were shorter in the reversible spinal state than in the decerebrate state.7. Control experiments showed that the responses to bradykinin and potassium were entirely due to the nervous outflow from the g.s. muscle. In contrast, intra-arterially applied 5-hydroxytryptamine influenced the s.c.t. cells via unknown additional sites of action.8. The results indicate that muscular group III and/or group IV units excitable by algesic substances do project on to neurones of the spinocervical tract. Furthermore it is concluded that the responses of s.c.t. neurones to activation of fine muscle afferents by algesic agents are subject to a descending control similar to the well known descending modulation of their responsiveness to cutaneous input. Therefore, in addition to serving as a cutaneous pathway the spinocervical tract may take part in muscular nociception.

Action Potentials↗

Responses of group IV afferent units from skeletal muscle to stretch, contraction and chemical stimulation.

In an attempt to differentiate between nociceptive group IV muscle receptors and "ergoceptive" ones, the discharges of single group IV fibres from skeletal muscle in response to local pressure, sustained stretch, repetitive contraction and intra-arterial injections of bradykinin, 5-hydroxytryptamine (5-HT), potasssium, phosphate, and lactate were studied in anesthetized cats.

Animals↗

Nervous outflow from skeletal muscle following chemical noxious stimulation.

1. In order to determine the nervous outflow from skeletal muscle during chemically induced muscle pain, the impulse activity of various types of muscle afferents in response to close intra-arterial injections of pain-producing substances (bradykinin, 5-hydroxytryptamine, histamine and potassium) was studied in anaesthetized cats using a single fibre recording technique.2. By administration of algesic agents in doses which produce pain in man and pain reactions in animals, about half of the group IV and two thirds of the group III muscle afferents could be activated. In contrast, group II and group I afferent units were usually not excited by chemical noxious stimulation. If effects at all occurred in the thick myelinated afferents, they consisted of a depression of the fibre activity rather than of an activation.3. The qualitative features of the discharges of group III muscle afferents induced by chemical stimulation resembled those of the group IV units very closely. The group III units differed from the group IV afferents in that their responses to a given dose of bradykinin were of greater magnitude.4. It is concluded that the chemically induced muscle pain is probably mediated by certain portions of the group IV and group III afferents, whereas the reactions of group II and group I units to algesic agents are such that a contribution to muscular chemo-nociception seems improbable.

Animals↗

The spinocervical tract as a possible pathway for muscular nociception.

In decerebrate and chloralose-anaesthetized spinal cats, micro-electrode recordings were made from axons of the spinocervical tract (SCT) during intra-arterial injection of bradykinin, 5-hydroxytryptamine and potassium into the gastrocnemius-soleus (GS) muscle. The results suggest that muscular group IV and group III afferent units which respond to the above painful stimulation project into the SCT. The portion of SCT units that could be activated by injections of these algesic substances into the GS-muscle was different in spinal and decerebrate preparations, showing that the SCT neurones are subject to a descending influence. It is concluded that the spinocervical tract, in addition to its function as a cutaneous sensory pathway, may serve as a pathway for muscular nociception in the cat.

Afferent Pathways↗

Muscular nociceptors.

The discharge characteristics of various types of muscle afferents in response to mechanical and chemical painful stimulation were studied in cats anaesthetized with chloralose. In a few experiments, heat was used as an additional stimulus. The results indicate that only among the fibre groups III and IV, units are regularly found that have high thresholds on mechanical and thermal stimulation, and that response to administration of algesic agents in pain-producing doses. The response behaviour of individual group III and group IV afferent units to the various stimuli was very similar, but when the fibre populations are compared, the group III afferents appeared to be more sensitive to the mechanical and chemical stimuli of this study. It is concluded that both the fibre groups III and IV include afferent units possessing receptive properties enabling them to serve as muscular nociceptors.

Action Potentials↗

Excitatory effects of 5-hydroxytryptamine, histamine and potassium ions on muscular group IV afferent units: a comparison with bradykinin.

The excitation of muscular group IV afferent units by the pain-producing substances 5-hydroxytryptamine (5-HT), histamine, and potassium ions was studied in cats and compared with the bradykinin effects of an earlier investigation. The substances were injected into the sural artery and the action potentials of single group IV afferent fibres from the gastrocnemius-soleus muscle were recorded extracellularly. About half of the 180 units tested with chemical stimulation could be excited by amounts of the above agents which are likely to be present in pathologically altered tissues. Of the tested substances, 5-HT was the most and potassium the least effective stimulant; in comparison with bradykinin, 5-HT was by far less potent, though. The molar ratios of approximately equivalent doses of bradykinin, 5-HT, histamine, and potassium were found to be about 1:30:66:4000. The threshold injection doses of KC1 for activation of muscular group IV units were such that an unspecific depolarizaing mode of action seems probable. Differences in the chemosensitivity of individual group IV units might be indicative of the existence of different receptor sites at the nerve endings. The sensitivity of muscle receptors with group IV afferent fibres to pain-producing substances--especially to bradykinin and 5-HT--supports the view that these units might participate in the mediation of muscle pain.

Animals↗

Evidence for the existence of different receptor sites for algesic agents at the endings of muscular group IV afferent units.

The hypothesis that different receptor sites for algesic agents exist at free nerve endings in skeletal muscle has been tested by administering bradykinin and 5-hydroxytryptamine (5-HT) repeatedly in anaesthetized cats and evaluating the response behaviour of single group IV afferent units from the gastrocnemius-soleus muscle. Repeated intraarterial administration of bradykinin at intervals of 1 and 2 min usually elicited fibre responses without tachyphylaxis. Injections of equieffective doses of 5-HT, however, given in the same manner evoked fibre reactions that were strongly tachyphylactic. In units responding to both bradykinin and 5-HT a refractoriness to 5-HT could be induced by repeated injections of this agent without impairing the stimulating potency of bradykinin on the same nerve ending. Such a lack of cross-tachyphylaxis seems to apply also to the effects of histamine on one side and bradykinin or 5-HT on the other. These findings suggest that bradykinin, 5-HT and probably histamine exert their excitatory action on muscular group IV afferent units via different receptor sites.

Animals↗

Muscle receptors with group IV afferent fibres responding to application of bradykinin.

In 60 anaesthetized cats the discharge characteristics of single group IV afferent fibres from skeletal muscle at rest, during local mechanical stimulation of the muscle, and in response to injections of bradykinin have been studied. 250 group IV fibres from the gastrocnemius-soleus muscle have been identified by their conduction velocity. Of these fibres 121 have been recorded from the dorsal root and 129 from the muscle nerve. A resting discharge was present in 52% of the dorsal root fibres and in 57% of the fibres recorded peripherally. Out of 203 units subjected to local mechanical stimulation of the muscle 9 responded to light, innocuous pressure; 129 fibres required strong, presumably noxious stimulation to be excited. The rest of 65 fibres could not be activated by the mechanical stimuli used. Intraarterial injection of bradykinin excited 88 out of 184 group IV fibres. Intramuscular injection of bradykinin was also found to be an effective stimulus. External application of bradykinin to the intact and to the dissected muscle nerve regularly had no excitatory effect on fibres being sensitive to intraarterially administered bradykinin. Injections of vasoactive drugs (nylidrine, noradrenaline) failed to affect the activity of group IV fibres responding to bradykinin. It is concluded that bradykinin is a potent stimulant for the intramuscular endings of afferent group IV fibres; the effective concentration lying within the range observed in pathologically altered tissues. This sensitivity to bradykinin together with a high mechanical threshold suggests that muscular group IV afferent units participate in the reception of muscular pain.

Animals↗