Influence of flupirtine on human lower limb reflexes

The influence of a single oral dose (400 mg) of flupirtine on lower limb reflexes was investigated in normal human subjects using H-reflex testing, flexor reflex testing and dynamic posturography. Flupirtine did not significantly change the latency of the H-reflex or the H_max/M_max ratio. Both, the first (F1) and the second (F2) components of the flexor reflex were significantly depressed. Flupirtine significantly decreased the size of the ML response following fast transient platform movements rotating toe-up around the ankle joint. We conclude that flupirtine acts on polysynaptic spinal pathways. In addition to its well known analgesic effect flupirtine might have a muscle relaxant effect.     

Cutaneous nociceptive facilitation of Ib heteronymous pathways to lower limb motoneurones in humans

The effects of tonic pain stimulation on heteronymous Ib pathways from the gastrocnemius medialis (GM) to the soleus (Sol) and to the quadriceps (Q) muscles were investigated in four healthy human subjects. Tonic pain stimulation was performed by subcutaneous injection of 0.5 mg levo-ascorbic acid or vitamin C (L-AS) in a volume of 0.5 ml on the dorsal surface of the ipsilateral foot. The mean curve of L-AS-induced pain sensation showed a steep rising phase reaching maximum intensity at 2–3 min, followed by a slow decay phase lasting about 15–20 min. Between about 5 and 20 min after injection, there was evidence of pure pain stimulation due to chemical activation of free nerve endings. During this interval, significant potentiation of Ib inhibition from GM to both Sol and Q motoneurones was observed. The time-course of these Ib heteronymous changes paralleled that of subjective pain sensation. These findings demonstrate that nociceptive discharge modifies the gain of Ib heteronymous effects in humans. Since the main function of these Ib pathways is to coordinate activity of muscles operating at different joints, it is suggested that nociceptive input may change muscle synergies by selecting specific subpopulations of Ib interneurones, thus contributing to establish appropriate adaptive motor strategies.     

Intraoperative recordings of spinal somatosensory evoked potentials to tibial nerve and sural nerve stimulation

Somatosensory evoked potentials (SSEPs) to stimulation of the tibial nerve at the knee (TN-K) and ankle (TN-A), and the sural nerve at the ankle (SN-A), were recorded from 3 or 4 spinal levels during surgery for scoliosis in 11 neurologically normal subjects. With stimulation of all 3 nerves, the propagation velocity along the spine was nonlinear: it was faster over cauda equina and midthoracic cord than over caudal spinal cord. Over the mid-thoracic cord, TN-K SSEP propagation was faster than that of TN-A and SN-A SSEPs, whereas over the caudal spinal cord these values were similar on stimulation of all 3 nerves. These data suggest that fast conducting second order afferent fiber systems contribute to spinal cord SSEPs evoked by stimulating both mixed and cutaneous peripheral nerves.     

Dorsal column stimulation does not inhibit segmental nociceptive reflexes of hind limbs

Stimulation of the dorsal columns has been shown to inhibit many indices of nociception. We report here that dorsal column stimulation does not inhibit two such nociceptive reflexes in the decerebrate cat: the flexion and the crossed extension reflex. In fact, such stimulation typically facilitates these reflexes. These findings suggest that the use of segmental nociceptive reflexes as models of pain perception may not be wholly appropriate.     

Comparative study of the nociceptive reflex and late components of the evoked somatosensory potential during stimulation of the sural nerve in healthy subjects

A study was carried out with 10 normal volunteers in order to find a correlation between nociceptive flexion reflexes from the biceps femoris muscle and the amplitude of the late component (N150-P220) of the vertex evoked potential elicited by sural nerve stimulations at various intensities randomly delivered. The range of stimulus varied from the perception threshold (usually 1 mA) to 2 times the reflex threshold. This latter parameter was usually found between 8 and 11 mA. While the nociceptive flexion reflex increased linearly as a function of stimulation intensity, the amplitude of N150-P220 was maximum at pain threshold and remained in plateau at this level or even slightly decreased as a function of stimulus intensity. No significant correlation was found between the recruitment curve of the nociceptive reflex and that of the late component of the evoked potential as a function of stimulus intensity. Functional implications of these data are discussed.     

Observations on electrical stimulation of lumbosacral nerve roots in children with and without lower limb spasticity

Selective functional posterior rhizotomy (SFPR) is a popular operation for the treatment of spasticity in children with cerebral palsy, but the physiologic basis of the procedure is poorly understood. As part of SFPR operations in 60 consecutive children, the responses to electrical stimulation of posterior lumbosacral roots and rootlets, and the corresponding anterior roots were studied. In addition, similar electrical stimulation of posterior roots was performed in four nonspastic control children. Sustained responses to 50 Hz stimulation, one of the criteria used to signify abnormality in the spastic children, was found frequently in the control children. Contralateral spreal to the lower limb muscles and suprasegmental spread to the upper limbs, face, and neck were determined to be the most valid criteria which differentiated abnormal from normal responses. Stimulation of anterior nerve roots at 50 Hz caused sustained responses and ipsilateral lower limb spread, at a low threshold compared to that of corresponding posterior roots. The results of this study bring into question the validity of some of the criteria that are used to select abnormal posterior rootlets in the SFPR procedure, and suggest criteria that may be more valid based on findings in nonspastic children.     

The sural nerve in familial dysautonomia.

In familial dysautonomia there are malfunctions of motor, sensory and autonomic systems. The sural nerve has reduced transverse fascicular area, diminished numbers of myelinated axons (particularly those of small diameter) and very few non-myelinated axons. Catecholamine containing endings are not found in accompanying arteries. These changes are compatible with reduced neuronal populations described in sympathetic and sensory ganglia. The observed pathology accounts for many of the clinical features of the disease and suggests an abnormality in intrauterine development.     

On the spinal pathways mediating scalp-SEPs to upper and lower limb nerve stimulation: case report and discussion

Scalp-SEPs to peroneal nerve stimulation were abnormal in a patient with an intradural meningeoma which was compressing the antero-lateral quadrant of the 1st and, partly, the 2nd cervical myelomers. In contrast, spine and scalp-SEPs were symmetrically normal during the sural, median and ulnar nerve stimulation of either side. On surgery, it was observed that the tumor had left the dorsal columns (DCs) almost unaffected. It is argued, in agreement with the bulk of experimental evidence, that in humans the scalp-SEPs to lower mixed nerve stimulation are also mediated, at the rostral cord level, by fast-propagating tracts ascending outside the DCs.     

Transperineurial arterioles in human sural nerve.

The perineurial sheath of nerve fascicles is a protective cellular layer that separates the endoneurium from the epineurium. Transperineurial arterioles (TPA) connect the endoneurial capillary plexuses to the epineurial arterial nutrient supply. Transperineurial arterioles are defined as any arteriole that is confined to a perineurial cell compartment, which would include all arterioles within the perineurium proper or within perineurial sleeves in the epi- or endoneurium. In this study of biopsied human sural nerves, three-dimensional reconstruction of one micron sections and ultrastructural analysis of step serials, we find that TPA are confined in open-ended perineurial sleeves by which they pass from the epineurium through the perineurial sheath proper into the endoneurium. Most TPA are terminal arterioles as evidenced by size (10-25 microns), morphological characteristics, and the fact that they connect with capillaries. Transperineurial arterioles gradually lose their continuous muscle coat and become post-arteriolar capillaries (PAC). Vascular segments that emerge into the endoneurium from the perineurial sleeves are generally of the PAC variety. Transperineurial arterioles and post-arteriolar capillaries are often associated with a plexus of unmyelinated nerve fibers. Axon varicosities exhibit a variety of morphologically distinct vesicles including dense-cored and a diversity of agranular vesicles. These findings suggest that TPA play a role in the neurogenic control of endoneurial blood flow.     

Application of immunohistochemical techniques to sural nerve biopsies.

The role of immunohistochemistry in the day-to-day diagnostic work of a peripheral nerve laboratory is not yet clearly established, although for conditions such as amyloid neuropathy, immunohistochemistry appears to be a useful adjunct to conventional techniques. Immunohistochemistry has provided new information about some neuropathies in which immune dysfunction is believed to play a central role. Immunohistochemical data about normal human nerve are scarce; a better appreciation of the normal cellular constituents of nerve, particularly the endoneurium, is needed. In the future, the techniques may be a means to understand better the pathogenesis of other types of neuropathy, such as inherited or toxic neuropathies, or to examine fundamental pathologic events such as axonal degeneration.     

Electrical stimulation reveals relatively ineffective sural nerve projections to dorsal horn neurons in the cat

Electrical stimulation of the sural nerve (SN) revealed input from sural nerve afferents to L6 and L7 dorsal horn neurons that were not apparent using natural mechanical stimuli, especially in cells with variable latency responses to SN stimulation. Nearly all (31/32) cells that had reliable, fixed latency responses to SN stimulation also had an excitatory receptive field (RF) in the region of skin innervated by the sural nerve (SN region). About one-third (20/57) of the cells with variable latency responses to SN stimulation, however, had an RF outside the SN region. Most (130/146) cells with no response to SN stimulation had RFs outside the SN region. There were no obvious differences between variable latency cells with RFs in the SN region vs those with RFs outside it in latency of response to SN stimulation, recording depth, RF sizes or modality properties. In a subsample of 31 postsynaptic dorsal column neurons all cells responding to SN stimulation also had an RF in the SN region. Strengthening of relatively ineffective projections from the sural nerve by lesions might be expected to lead to an increase in the proportion of cells responding with impulses to natural stimulation of the skin innervated by the sural nerve, and, hence, to an increase in average RF size.     

Intense peripheral electrical stimulation differentially inhibits tail vs. limb withdrawal reflexes in the rat

In an on-going study on mechanisms by which activation of sensory afferents regulates nociception, high-intensity, low-frequency electrical stimulation was applied to previously defined meridian and non-meridian points of the hindlimb or forelimb, and the effects measured on the withdrawal reflex of the tail or limb in the lightly anesthetized rat. Withdrawal was evoked by application of noxious radiant heat to the tip of the tail or to the plantar surface of a hindpaw or forepaw. Parameters of conditioning electrical stimulation were 2 ms pulses at 4 Hz for 20 min at 20 × threshold (20–30 mA) where threshold was the minimum intensity which evoked muscle twitch. In experiments on tail withdrawal, stimulation applied to meridian points fengshi (GB-31), femur-futu (ST-32) and zusanli (ST-36) of the hindlimb or to wai-kuan (TH-5) and hoku (LI-4) of the forelimb increased the latency of the withdrawal reflex to 70–100% of the maximum possible inhibition (MPI) during the stimulation. Inhibition persisted for more than 1 h after the end of stimulation. Bilateral stimulation of hindlimb meridian points evoked a greater inhibition during the stimulation ( > 95% of the MPI); the inhibition persisted for 40 min. Stimulation of non-meridian sites in hindlimb or forelimb inhibited the withdrawal reflexes by 45–50% of the MPI during the stimulation only. Thus, the evoked inhibition has two components, a brief effect elicited by non-meridian point stimulation and a persistent post-stimulation effect produced only upon stimulation of meridian points. Stimulation produced little effect on nociceptive limb withdrawal reflexes. The results suggest that high-intensity, low-frequency electrical stimulation of meridian points produced a long-lasting, extrasegmental inhibition of the tail withdrawal but not of limb withdrawal reflexes. This differential inhibition may be due to differences in neuronal circuitry and CNS modulatory control mechanisms. The persistent inhibition appears to be dependent on the site of stimulation because it is not evoked by stimulation of sites outside of meridian points.     

Effects of temporal-parietal lesions on the somatosensory P3 to lower limb stimulation.

Temporal-parietal junction lesions reduce the auditory and upper limb somatosensory P3 event-related potential (ERP) to target and novel stimuli. The current study examined the somatosensory P3 to target and novel stimuli delivered to the sole of the foot in patients with unilateral temporal-parietal lesions (n = 6). Age-matched controls (n = 10) generated a parietal maximal target P3 and a frontal-central maximal novelty P3 ERP to foot stimulation. Unilateral temporal-parietal lesions abolished target and novelty P3 responses over all scalp sites for stimuli delivered contralateral to the lesion. The P3 was also reduced to ipsilateral stimuli at electrodes over the lesioned hemisphere with partial P3 preservation observed at electrode sites over the non-lesioned hemisphere. These results parallel the findings for upper limb stimulation and support the critical role of temporal-parietal cortex in P3 generation.     

Cutaneous nerve stimulation and motoneuronal excitability: I, soleus and tibialis anterior excitability after ipsilateral and contralateral sural nerve stimulation.

Modification of soleus and anterior tibial anterior horn cell excitability following ipsilateral and contralateral stimulations of the sural nerve was studied by either the H reflex (for the soleus and anterior tibial muscles) or the F response (for the anterior tibial muscles). Several intensities of stimulation were employed. In every instance the recovery curves showed two distinct peaks of facilitation, which appeared with the same delay in muscles with antagonist functions. Also, reciprocal facilitation and inhibition phenomena which occurred after a 25 ms delay and which lasted more than 1000 ms were observed. The intervention of suprasegmentary neuronal mechanisms is proposed to explain the facilitation peaks, while the longer lasting phenomena are probably dependent on spinal processes.     

Characteristics of sympathetic reflexes evoked by electrical stimulation of phrenic nerve afferents.

In chloralose-anaesthetized cats, sympathetic reflex responses were recorded in left cardiac and renal nerve during stimulation of afferent fibres in the ipsilateral phrenic nerve. In cardiac nerve, a late reflex potential with a mean onset latency of 75.6 +/- 13.8 ms was regularly recorded which, in 20% of the experiments, was preceded by an early, very small reflex component (latency between 35 and 52 ms). In contrast, in renal nerve only a single reflex component after a mean latency of 122.1 +/- 13.1 ms was observed. Bilateral microinjections of the GABA-agonist muscimol into the rostral ventrolateral medulla oblongata resulted in a nearly complete abolition of sympathetic background activity and in an 88% reduction of the late reflex amplitude with only small effects on the latency of the evoked potentials. Under this condition, an early reflex component was never observed to appear. After subsequent high cervical spinalization, the residual small potentials which persisted after bilateral muscimol injections were completely abolished and in cardiac nerve an early reflex potential with a mean latency of 45 +/- 10 ms was observed in all but one experiment. The early reflex was therefore referred to as a spinal reflex component which, however, is suppressed in most animals with an intact neuraxis. In the renal nerve a spinal response was only observed in one experiment after spinalization. The results suggest that sympathetic reflexes evoked by stimulation of phrenic nerve afferent fibres possess similar spinal and supraspinal pathways as previously described for somato-sympathetic and viscero-sympathetic reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Conduction characteristics of somatosensory evoked potentials to peroneal, tibial and sural nerve stimulation in man

Lumbar spine and scalp short latency somatosensory evoked potentials (SSEPs) to stimulation of the posterior tibial, peroneal and sural nerves at the ankle (PTN-A, PN-A, SN-A) and common peroneal nerve at the knee (CPN-K) were obtained in 8 normal subjects. Peripheral nerve conduction velocities and lumbar spine to cerebral cortex propagation velocities were determined and compared. These values were similar with stimulation of the 3 nerves at the ankle but were significantly greater with CPN-K stimulation. CPN-K and PTN-A SSEPs were recorded from the L3, T12, T6 and C7 spines and the scalp in 6 normal subjects. Conduction velocities were determined over peripheral nerve-cauda equina (stimulus-L3), caudal spinal cord (T12-T6) and rostral spinal cord (T6-C7). Propagation velocities were determined from each spinal level to the cerebral cortex. With both CPN-K and PTN-A stimulation the speed of conduction over peripheral nerve and spinal cord was non-linear. It was greater over peripheral nerve-cauda equina and rostral spinal cord than over caudal cord segments. The CPN-K response was conducted significantly faster than the PTN-A response over peripheral nerve-cauda equina and rostral spinal cord but these values were similar over caudal cord. Spine to cerebral cortex propagation velocities were significantly greater from all spine levels with CPN-K stimulation. These data show that the conduction characteristics of SSEPs over peripheral nerve, spinal cord and from spine to cerebral cortex are dependent on the peripheral nerve stimulated.