High Threshold Cutaneous Afferents Research Articles

Discrete field potentials produced by coherent activation of spinal dorsal horn neurons.

In addition to the action potentials generated by the ongoing activation of single dorsal horn neurons in the anesthetized cat, we often recorded small negative field potentials with a fast-rising phase and a slow decay (dIFPs). These potentials could be separated in different classes, each with a specific and rather constant shape and amplitude. They were largest in spinal laminae III-V and gradually faded at deeper locations, without showing the polarity reversal displayed at these depths by the focal potentials produced by stimulation of muscle and cutaneous afferents. We propose that the dIFPs are postsynaptic field potentials generated by strongly coupled sets of dorsal horn neurons displaying a spatial orientation that generates closed field potentials in response to stimulation of high-threshold cutaneous and muscle afferents. These neuronal sets could form part of the spinal inhibitory circuitry that mediates presynaptic inhibition and Ib non-reciprocal postsynaptic inhibition and could be involved in the sensory-motor transformations activated by stimulation of high-threshold cutaneous afferents.

Primary afferent depolarization of muscle afferents elicited by stimulation of joint afferents in cats with intact neuraxis and during reversible spinalization.

1. In the anesthetized and artificially ventilated cat, stimulation of the posterior articular nerve (PAN) with low strengths (1.2-1.4 x T) produced a small negative response (N1) in the cord dorsum of the lumbosacral spinal cord with a mean onset latency of 5.2 ms. Stronger stimuli (> 1.4 x T) produced two additional components (N2 and N3) with longer latencies (mean latencies 7.5 and 15.7 ms, respectively), usually followed by a slow positivity lasting 100-150 ms. With stimulus strengths above 10 x T there was in some experiments a delayed response (N4; mean latency 32 ms). 2. Activation of posterior knee joint nerve with single pulses and intensities producing N1 responses only, usually produced no dorsal root potentials (DRPs), or these were rather small. Stimulation with strengths producing N2 and N3 responses produced distinct DRPs. Trains of pulses were clearly more effective than single pulses in producing DRPs, even in the low-intensity range. 3. Cooling the thoracic spinal cord to block impulse conduction, increased the DRPs and the N3 responses produced by PAN stimulation without significantly affecting the N2 responses. Reversible spinalization also increased the DRPs produced by stimulation of cutaneous nerves. In contrast, the DRPs produced by stimulation of group I afferents from flexors were reduced. 4. Conditioning electrical stimulation of intermediate and high-threshold myelinated fibers in the PAN depressed the DRPs produced by stimulation of group I muscle and of cutaneous nerves. 5. Analysis of the intraspinal threshold changes of single Ia and Ib fibers has provided evidence that stimulation of intermediate and high threshold myelinated fibers in the posterior knee joint nerve inhibits the primary afferent depolarization (PAD) of Ia fibers, and may either produce PAD or inhibit the PAD in Ib fibers, in the same manner as stimulation of cutaneous nerves. In 7/16 group I fibers the inhibition of the PAD was increased during reversible spinalization. 6. The results obtained suggest that intermediate and high-threshold myelinated fibers in the PAN have the same actions on Ia and Ib fibers as intermediate and high-threshold cutaneous afferents and may therefore be considered as belonging to the same functional system. They further indicate that in anesthetized preparations the pathways mediating the PAD of group I fibers, as well as the pathways mediating the inhibition of the PAD, may be subjected to a descending control that is removed by spinalization.

Silent period induced by cutaneous stimulation

An electrical stimulus applied to a cutaneous nerve during isometric muscle contraction causes a suppresson of EMG acivity (silent period) followed by a rebound. Te extent of inhibition is related to the stimulus intensity as the silent period is more evident when stimulation is perceived as painful. The silent period is present in different limb and cranial muscles after stimulation of the same cutaneous nerve and in the same muscle after stimulation of distant cutaneous nerves. It also synchronously in antagonist muslces. Within the silent period induced after cutaneous stimulation the maximal inhibition on the opponens pollicis motor neuron pool, as tested by the motor response evoked after transcranial cortical stimulation, occurs between 50 and 70 msec. Using the double stimulus technique to study the recovery cycle, the silent period is present at interstimulus intervals as low as 100 msec, and does not habituate with trains of stimuli at frequencies up to 5 Hz. Our results suggest that motor neuron inhibition from nociceptive stimulation may be mediated by Renshaw cells directly activated by high threshold cutaneous afferents.

Excitatory responses of the dorsal root discharge to stimulation of cutaneous and muscle afferents in the cat

Excitatory responses of the dorsal root discharge (DRD) consisting in transient increase in its frequency have been studied in non-anaesthetized low spinal cats. They were evoked by stimulation of cutaneous nerves (superficial peroneal and posterior tibial) and muscle nerves (gastrocnemius-soleus and posterior biceps-semitendinosus), recorded from the central cut ends of single fibres of L7 dorsal roots. The excitatory responses were elicited by single volleys in low threshold cutaneous and group II muscle afferents. Group III afferents of gastrocnemius-soleus nerve were also effective. Increase in strength of stimulation of posterior biceps-semitendinosus nerve from 4T to 40T which activated group III muscle afferents significantly decreased the excitatory effects of the DRD. Incidence of excitatory responses of the DRD to volleys both in low and high threshold cutaneous afferents, was 100%. Frequency of occurrence of excitatory effects to volleys in group II muscle afferents ranged from 23% to 43% (for responses to posterior biceps-semitendinosus and gastrocnemius-soleus volleys, respectively). It was increased to 47% and 72% when excitatory effects were elicited by group III afferent volleys. These findings indicate that only some types of afferent fibres evoke excitatory responses of the DRD. Variable incidence of the excitatory responses to stimulation of cutaneous and muscle afferents suggests important difference in effectiveness of connections between both types of fibres and interneurones generating the DRD.

The R3 component of the blink reflex in man: a reflex response induced by activation of high threshold cutaneous afferents

Ten successive experiments were carried out in 10 volunteers to compare the physiological properties of R2 and R3 components of the blink reflex. The electrical activation threshold of the R3 component was found to be significantly higher than that of the R2 response and was more susceptible to anaesthetic blocking of the peripheral afferents. This result suggests that the R3 component is induced by the activation of a different population of peripheral afferents from the R2 component. A recovery cycle study performed using a double stimulus showed that R3 is inhibited to a greater extent and for a longer time than R2. The temporal relationship of R3 to the voluntarily produced blink demonstrates that R3 is not a voluntary response to electrical stimulation. In conclusion, these experiments support the existence of an independent R3 component and its relationship with the activation of small diameter and higher threshold afferent fibres, perhaps nociceptive ones.

Ultrastructural analysis of axosomatic contacts on functionally identified primate spinothalamic tract neurons.

The morphology and frequency of axosomatic contacts on three functionally identified primate spinothalamic tract (STT) cells were analyzed at the electron microscopic level. The STT cells analyzed were wide-dynamic-range neurons responsive to activation of low- and high-threshold cutaneous afferents innervating the foot. The somas were located in the lateral border of lamina V; the dendritic trees were oriented dorsally and were very extensive. Numerous spinelike appendages were observed emanating from two of the cell bodies. Terminal types contacting the cell bodies were categorized at several different layers through each neuron. Six morphologically different terminal types were established following analysis of serial sections. Profiles classified as round (R) terminals containing round clear vesicles and zero or one dense-core vesicle made up over 50% of the total population in contact with the STT somas. Profiles containing round clear vesicles and two to four small-diameter dense-core vesicles (D1 category) made up approximately 10% of the population in contact with each soma. Flat (F) terminals with oblong or flattened clear vesicles made up approximately 8% of the population. The remaining three categories (D2, L1, and L2) distinguished by the number and size of the dense-core vesicles made up a small percentage of the total population in contact with the cell bodies. The distribution of terminal types on the soma proper versus somatic spines was also determined for one cell. The proportions of the six terminal types contacting the soma of these cells were very similar, although the physiological characteristics of each cell were different. However, the relative proportions of terminal types on these three lamina V STT cell bodies were different from those previously reported contacting somata in lamina V, suggesting that there may be a unique innervation of STT cells that differentiates them from other cell types in lamina V.

Changes in segmental reflexes following chronic spinal cord hemisection in the cat. II. Conditioned monosynaptic test reflexes.

In a companion paper (Hultborn & Malmsten 1983) it was described that ventral root discharges to stimulation of peripheral nerves became larger on the side of a chronic spinal hemisection (left) than on the other side. In the present paper, based on the same experiments, conditioning of monosynaptic test reflexes was used to study changes of both excitatory and inhibitory effects on specified motoneuronal pools. Conditioning stimulation was given to IA afferents (reciprocal Ia inhibition, presynaptic inhibition of Ia fibers), high threshold muscle afferents, low and high threshold cutaneous afferents and motor axons (recurrent inhibition). A comparison of the efficacy of conditioning stimuli on the two sides showed that facilitatory effects were larger on the side of hemisection in a clear majority of cases. Inhibition was almost always either more efficient on the side of hemisection or equally efficient on the two sides. In control cats, facilitatory effects tended to be larger on the right side, while the results for inhibitory conditioning generally showed no clear side-bias. The increase in facilitatory effects after lesions may contribute to symptoms of spasticity.

Primary afferent depolarization in the cervical enlargement of cats evoked by activation of cervical sensory nerves

Depolarization of primary afferent terminals in the cervical enlargement of the spinal cord evoked by activation of sensory nerves of the upper cervical segments (C2) was studied in cats anesthetized with pentobarbital. It was shown that low-threshold muscular and high-threshold cutaneous afferents of nerves of the forelimb were depolarized most strongly. Parallel with this depolarization, prolonged (over 0.5 sec) inhibition of the monosynaptic and polysynaptic flexor reflex developed. It is suggested that these influences are transmitted via pathways running in the posterior and lateral white columns. The results are discussed in connection with regulation of postural motor activity in vertebrates.

Inhibitory actions from low and high threshold cutaneous afferents on groups II and III muscle afferent pathways in the spinal cat

The inhibitory effects caused by volleys in cutaneous afferents on the transmission through some polysynaptic segmental pathways activated by high threshold muscle afferents were studied in chloralose anesthetized, spinal cats. Pathways studied were groups II and III to motoneurones as well as group II to primary afferents. The results suggested that two different mechanisms were involved. One mechanism, with a very slow time course (duration more than 400 ms), is suggested to be an example of presynaptic inhibition between different primary afferent systems. This mechanism required high threshold (greater than or equal to 1.6T) conditioning shocks, and appeared simultaneously with the component II dorsal root potential being evoked by the cutaneous afferent volley. The other mechanism, with a faster time course (duration always below 300 ms), was dependent upon low threshold (less than or equal to 1.5T) cutaneous conditioning volleys. This inhibitory interaction could not be ascribed to the same presynaptic mechanism, but is suggested to be an example of postsynaptic inhibition at an interneuronal level. The presumed disynaptic excitatory pathway from group II muscle afferents to flexor motoneurones was not inhibited by cutaneous conditioning shocks, but could on the contrary be facilitated by activity in low threshold cutaneous afferents, probably at the only interneurone involved in this group II pathway.

Presynaptic inhibition evoked by stimulation of relatively high-threshold cutaneous afferents

Presynaptic inhibition evoked by stimulation of relatively high-threshold cutaneous afferents

Synaptic actions of peripheral nerve impulses upon Deiters neurones via the climbing fibre afferents.

1. The cerebellar integration of sensory inputs to Deiters neurones was studied in cats under Nembutal anaesthesia.2. Stimulation of peripheral nerves produced in the Deiters neurones a sequence of an initial excitatory post-synaptic potential (e.p.s.p.) and a later inhibitory post-synaptic potential (i.p.s.p.), or a relatively small e.p.s.p.3. The Deiters neurones were classified as forelimb (FL)- or hind limb (HL)-type cells according to the location of the most effective peripheral nerve. In the FL cells stimulation of the forelimb nerves produced the e.p.s.p.-i.p.s.p. sequence (dominant response), while stimulation of the hind limb nerves was ineffective or produced the small e.p.s.p. (non-dominant response). In contrast, in the HL cells the non-dominant response was evoked from the forelimb nerves, and the dominant response from the hind limb nerves.4. The stimulus intensity-response relation indicates that Group I and II muscle afferents and low and high threshold cutaneous afferents contribute to the dominant and non-dominant responses.5. Antidromic identification of these Deiters neurones revealed that 90% of the HL cells and 85% of the FL cells project to the lumbo-sacral and cervico-thoracic segments of the spinal cord, respectively, while 10% of the HL cells and 15% of the FL cells innervate the cervico-thoracic and lumbo-sacral segments, respectively.6. The mean latency of the e.p.s.p. evoked from the forelimb nerves was 14 msec in the FL cells and 13 msec in the HL cells, and the latency of the e.p.s.p. evoked from the hind limb nerves was 17 msec in the FL cells and 18 msec in the HL cells. The later i.p.s.p. regularly followed the onset of the e.p.s.p. with a delay of 3-5 msec.7. The dominant and non-dominant responses in both types of cells exhibited the following three characteristic features: (i) a strong depression after conditioning stimulation of the inferior olive, (ii) an increase of the inferior olivary excitability during the responses, and (iii) a striking frequency depression with stimulation at relatively low frequency (5-10/sec).8. Consequently it was concluded that all of the responses were produced through the climbing fibres originating from the inferior olive, the i.p.s.p.s due to inhibition from Purkyne cells activated by the climbing fibres and the e.p.s.p.s due to excitation from the collaterals of the climbing fibres.

Effects of some narcotic analgesics upon the monosynaptic reflex inhibition from muscular and cutaneous afferents in spinal cord of the cat.

It has been know that, at a small dose, narcotic analgesics depress polysynaptic reflex activity in the spinal cats (1) and nociccptive reflexes in the spinal rats (2), as well as in spinal cats and dogs (3-6), where they do not depress, or slightly enhace the monosynaptic reflex (3). In order to explain this depression induced by narcotic analgesics, it has been suggested that the interneurons responsible for mediation of the polysynaptic reflex are suppressed (3). Further, for a remarkable depression of nociceptive reflex discharges from high threshold cutaneous afferents by morphine and pethidine, it has been suggested that some interneurons activated by such small fibers of the cutaneous nerve might be inhibited (7). On the other hand, large doses of morphine (15-20 mg/kg) has been reported to potentiate the Group la inhibition and depress the recurrent inhibition via Renshaw cell arcs in decerebrate cats (8). However, it remains still unknown whether narcotic analgesics may depress spinal interneurons generally or special interneurons specifically. Therefore, it was attempted in the present study to find either one of these. As a test system, the effects of some narcotic analgesics upon the inhibitory influences to the extensor monosynaptic reflex from flexor reflex afferents were studied using unanesthetized low spinal cats.

EFFECTS OF SOME NARCOTIC ANALGESICS UPON THE MONOSYNAPTIC REFLEX INHIBITION FROM MUSCULAR AND CUTANEOUS AFFERENTS IN SPINAL CORD OF THE CAT

It has been know that, at a small dose, narcotic analgesics depress polysynaptic reflex activity in the spinal cats (1) and nociceptive reflexes in the spinal rats (2), as well as in spinal cats and dogs (3-6), where they do not depress, or slightly enhace the monosynaptic reflex (3). In order to explain this depression induced by narcotic analgesics, it has been suggested that the interneurons responsible for mediation of the polysynaptic reflex are suppressed (3). Further, for a remarkable depression of nociceptive reflex discharges from high threshold cutaneous afferents by morphine and pethidine, it has been suggested that some interneurons activated by such small fibers of the cutaneous nerve might be inhibited (7). On the other hand, large doses of morphine (15-20 mg/kg) has been reported to potentiate the Group la inhibition and depress the recurrent inhibition via Renshaw cell arcs in decerebrate cats (8).However, it remains still unknown whether narcotic analgesics may depress spinal interneurons generally or special interneurons specifically. Therefore, it was attempted in the present study to find either one of these. As a test system, the effects of some narcotic analgesics upon the inhibitory influences to the extensor monosynaptic reflex from flexor reflex afferents were studied using unanesthetized low spinal cats.

Pyramidal influences on interneurons of spinal segmentary reflector arcs in cat

Microelectrode discharges of potentials have been realized from segmentary interneurons of the dorsal horn and intermediate nucleus of the spinal cord in cat at the L6–L7 level by electrical stimulation of the sensorimotor region of the brain cortex. It has been established that corticifugal influences on segmentary interneurons of the system of the flexor reflex and on neurons activated by high threshold muscle afferents (groups Ib, II, and III), or high threshold cutaneous afferents are predominantly excitatory. Interneurons activated by muscle afferents of group Ia or by the lowest threshold cutaneous fibers are weakly subjected to pyramidal influences. The mean latencies of excitatory postsynaptic potentials (EPSP's) and discharges evoked under the influence of pyramidal volley, for the neurons under study in the system of afferents of the flexor reflex are equal to 11.8±2.6 and 20.1±1.8 msec, respectively; for interneurons, excited only by high threshold muscle afferents, they are equal to 15.5±3.6 and 16.3±2.2 msec, respectively; and for interneurons, excited by high threshold cutaneous fibers they are equal to 11.8±2.6 and 18.3±1.4 msec, respectively. Possible pathways of activating segmentary interneurons from the lateral sensorimotor region of the brain cortex have been discussed.