Elsevier

Brain Research

Volume 818, Issue 1, 6 February 1999, Pages 12-22
Brain Research

Research report
Presynaptic excitability changes of group Ia fibres to muscle nociceptive stimulation in humans

https://doi.org/10.1016/S0006-8993(98)01253-0Get rights and content

Abstract

Tonic muscle nociceptive discharge evoked chemically from the foot extensor digitorum brevis muscle in man produces a depression of Ia excitation and Ib inhibition of the soleus (Sol) motoneurones (Mns). The possibility that both these changes partly result from presynaptic inhibition of Ia fibres projecting to Sol Mns and to interneurones mediating group I non-reciprocal inhibition is tested. Convergence of Ia fibres on these interneurones was deduced from evidence that reducing the excitatory effect of the extensor Ia fibres (by potentiation of their presynaptic inhibition) resulted in Ib disinhibition. Nociceptive-induced potentiation of Ia presynaptic inhibition was deduced from the following congruent results obtained by two independent methods: (1) depression of heteronymous Ia monosynaptic facilitation of the quadriceps muscle to Sol Mns; (2) potentiation of presynaptic inhibition of Sol Ia fibres evoked by mechanical activation of the tibialis anterior primary spindle afferents. It is concluded that nociceptive volleys arising from dorsal foot muscles facilitate the activity of interneurones intercalated in pathways responsible for presynaptic inhibition of Sol Ia fibres. It is also proposed that the same Ia presynaptic inhibition depresses the excitability of interneurones mediating group I non-reciprocal inhibition, thus resulting in Ib disinhibition of Sol Mns.

Introduction

It is well established that the synaptic effectiveness of muscle and cutaneous afferents is controlled by specific sets of interneurones making axo-axonic synapses with afferent fibre terminals in the spinal cord. The existence of presynaptic control mechanisms implies that the peripheral information transmitted by a given set of afferent fibres is transformed before it reaches second-order cells. It follows that the presynaptic, unlike the post-synaptic control mechanism allows selective control of neuronal responses to synaptic input (see Ref. [40]).

Activity in many sensory afferents results in presynaptic modulation of Ia terminals and consequently in a variation in size of monosynaptic Ia excitatory post-synaptic potentials in motoneurones (Mns) [7]. In particular, the background Ia presynaptic inhibition is enhanced by the discharge of other Ia fibres and Ib afferents [4]. Potentiation of presynaptic inhibition of Ia fibres has also been observed after stimulation of low- and high-threshold cutaneous afferents in humans with chronic spinal lesions [31], similar to those seen in the spinal cat after injection of DOPA [1]. On the other hand, depression of Ia presynaptic inhibition has been observed after activation of intermediate and high-threshold cutaneous and joint afferents [30]and low-threshold cutaneous afferents 24, 18. Experiments in animals have shown that besides segmental influences, Ia presynaptic inhibition is modulated by many motor centres in the brain (see Ref. [3]). Human experiments have confirmed that Ia presynaptic inhibition is controlled during various voluntary and postural movements 17, 20, 5, 25. It has been proposed that decreased presynaptic inhibition allows Ia activity to contribute to excitation of voluntarily activated Mns and prevents activation of Mns not involved in the contraction, thus increasing motor contrast.

In a previous study in humans [35]undertaken to examine changes in Ib inhibitory pathways during painful stimulation of the extensor digitorum brevis muscle (EDB), it was observed that tonic activation of nociceptive afferents from this muscle produced a similar depression of monosynaptic excitation (H-reflex) and Ib disynaptic inhibition of soleus (Sol) Mns. In addition to post-synaptic effects, nociceptor-induced presynaptic changes in Ia afferents contacting both Sol Mns and interneurones mediating group I non-reciprocal inhibition is another possibility. Assuming that in man, not only Mns but also interneurones mediating group I non-reciprocal inhibition (once known as Ib interneurones) receive substantial monosynaptic excitation from group Ia fibres, as they do in animals [14], it is conceivable that nociceptor-induced increase in presynaptic inhibition of the Ia excitatory post-synaptic potentials could result in depression of Ia monosynaptic and Ib disynaptic pathways to Sol Mns.

Section snippets

Methods

The experiments were carried out with five healthy volunteers (two females, three males), aged 24–39 years. The experiments were approved by the ethical committee and were performed in accordance with the ethical standards laid down by the 1964 Declaration of Helsinki. The subjects gave their informed consent and were known from previous experiments to be suitable for this experimental procedure.

Subjective pain sensation after l-AS injection in the EDB

The nociceptive effects of l-AS are due to a local increase in tissue concentrations of hydrogen ions (paper in preparation), which is known to activate myelinated and unmyelinated nociceptive peripheral fibres [13]. Injection of 30 mg l-AS in a volume of 0.3 ml into the belly of the EDB caused a fully reversible pain sensation which reached a maximum within 2 min of the injection, and gradually decreased to zero in 10–15 min (Fig. 1A). Qualitatively, it was a compression-like pain of the foot

Discussion

Tonic nociceptive stimulation applied to the belly of the EDB resulted in long-lasting depression of Ia excitation (H-reflex) and Ib inhibition of Sol Mns. The present study was designed to verify whether presynaptic inhibition of Ia terminals could contribute to these changes. Assuming, in fact, that muscle nociceptive discharges from EDB potentiated presynaptic inhibition of the Ia fibres projecting to Sol Mns as well as those projecting to interneurones mediating Ib inhibition from GM to Sol

Acknowledgements

I wish to thank all the volunteers who participated in this study, and Drs. R. Spidalieri and A. Zalaffi for their unfailing assistance during the experiments. This work was supported by research grants from Italian MURST (60%) and Italian CNR.

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