Evidence for thoracolumbar spinal cord processing of inflammatory, but not acute colonic pain

The lower bowel is innervated by visceral afferents projecting to the lumbosacral and thoracolumbar spinal segments. The present study tested the hypothesis that sensory processing from the normal colon occurs in the lumbosacral spinal cord with little or no activity in the thoracolumbar segments. Following colonic inflammation, viscerosensory processing in the thoracolumbar spinal cord is recruited, contributing to visceral hyperalgesia. A baseline visceromotor reflex to colorectal distention recorded in intact rats was eliminated following bilateral L6-S3 dorsal rhizotomies. The visceromotor reflex recovered to 29% of baseline following colonic inflammation. These results suggest that visceral hyperalgesia and referred pain in patients with lower bowel disorders partly result from novel viscerosensory processing in the thoracolumbar spinal cord.     

Dermorphin inhibits spinal nociceptive flexion reflex in humans

Dermorphin (D) is a potent opiate-like peptide isolated from the skin of some species of frogs. Experimental studies in animals indicate that D has a potent antinociceptive effect, while no investigation exists about its analgesic properties in humans. Our study shows that i.v. infusion of 0.16 mg/kg D induces a marked and long-lasting increase in the threshold of nociceptive flexion reflex in healthy volunteers. This effect is also evident in a complete chronic spinal subject, showing that D depresses the nociceptive transmission mainly acting at spinal level. Naloxone, while fully antagonizing the effects of morphine and enkephalin analogue, is able to reverse only partly (ca. 50%) the depressive effect of D on nociceptive spinal reflex. This fact may suggest that D interacts with different spinal opiate receptor populations in inducing analgesia.     

Spinal and cortical inhibition in Huntington's chorea.

In this article we studied spinal and cortical inhibitory mechanisms in patients with Huntington's disease. To evaluate spinal cord inhibitory circuitries, we assessed reciprocal inhibition between antagonist forearm muscles and the recovery cycle of the H reflex in the flexor carpi radialis. Patients showed a significant decrease in the presynaptic phase of reciprocal inhibition reaching a minimum at the conditioning-test interval of 20 msec and an abnormal facilitation of the test H reflex at the conditioning test interval of 40 to 60 msec. Throughout its time course (10-200 msec), the H reflex recovery cycle showed a more prominent facilitation in patients than in control subjects. To assess whether the observed pathophysiological abnormalities might have arisen from an abnormal motor cortical excitability, we examined the recovery cycle of the motor potentials evoked by paired transcranial magnetic stimuli. We found that the inhibitory mechanisms controlling motor cortical excitability were normal. An interpretation of the spinal cord abnormalities is that the intrinsically normal but deafferentated motor cortex in Huntington's disease partly loses its inhibitory control, thus disinhibiting spinal cord circuitry. Our findings from paired transcranial magnetic stimulation suggest that cortical motor areas are not hyperexcitable in Huntington's disease. Hence, the postulated thalamocortical overactivity in experimental models of Huntington's disease needs to be reappraised.     

The clinical neuropathology of spinal cord injury. A guide to the future

The neuropathology of spinal cord injury (SCI) is reviewed in the light of clinical problems and as a guide to future research. The pathology of SCI in the acute stage suggests that the spinal cord may be partly preserved even in the most severe injuries. This finding emphasises the need for great care in roadside management. In the acute phase there are irreversible changes and possibly reversible changes which have not been adequately identified. Even a small percentage of nerve fibres escaping the initial injury would be of great benefit to the patient. In the subacute stage when transynaptic degeneration is proceeding there may also be associated functional changes leading to abnormal reflex activity. It is possible through an improved understanding of the neuropathology and neurophysiology of the isolated or partly isolated segments of the cord that new reflex connections may be stimulated to develop by artificial means. In the chronic stage there are well recognised complications such as osteoarthrosis with spinal stenosis, post-traumatic syringomyelia and traumatic nerve root neuroma formation, which may lead to clinical deterioration and which may be amenable to treatment. In a more theoretical sense it is possible that improved understanding of CNS plasticity and transplant neurobiology using recombinant DNA technology, grafting and 're-education' of the regenerated tissues may be rewarding in the longterm future. Although this outcome is entirely hypothetical at this stage basic research deserves great emphasis.     

Colonosphincteric electromyographic responses to sacral root stimulation: evidence for a somatosympathetic reflex

Abstract  The aim of the present study was to determine the effects of selectively stimulating the afferent fibres running in the dorsal sacral roots (S1, S2, S3) and the somatic (radial and sciatic) nerves on colonic and internal anal sphincter (IAS) electromyographic (EMG) activity in anaesthetized cats to try to understand how sacral nerve stimulation can improve fecal continence in human. Electrically stimulating the afferent fibres present in the sacral dorsal roots and somatic nerves inhibited the colonic spike potential frequency ( n  = 97) and increased the slow variations in the sphincteric membrane potential ( n  = 76). These effects were found to have disappeared after administering an α-noradrenergic receptor blocker ( n  = 64) or sectioning the sympathetic efferent fibres innervating these organs ( n  = 69) suggesting the involvement of the sympathetic system in the effects observed. Moreover, no significant differences were observed between the effects of sacral dorsal root vs somatic nerve stimulation on colonic and sphincteric EMG activity. In conclusion, the data obtained here show that neurostimulation applied to the sacral spinal roots may improve fecal continence by inhibiting colonic activity and enhancing IAS activity via a somatosympathetic reflex.     

The effect of vesical filling and voiding on the anorectal function with evidence of a `vesico-anorectal reflex''

The aim was to evaluate the effect of vesical filling and voiding on anal continence and rectal pressure. Fourteen healthy volunteers (age 37.2 +/- 9.6 years; 10 men, four women) were studied. The response of the rectal pressure and EMG of the external (EAS) and internal (IAS) anal sphincters to slow vesical filling and voiding was recorded before and after individual anaesthetization by xylocaine of the EAS, rectum and urinary bladder. Saline instead of xylocaine was used as control testing. The rectal pressure and EAS EMG activity showed no response to vesical filling (P > 0.05, P > 0.05, respectively) while a momentary increase in both parameters occurred upon voiding (P < 0.05, P < 0.01, respectively). The IAS EMG exhibited no response to either filling or voiding. Separate anaesthetization of either of the EAS, rectum or bladder produced no response of the rectal pressure or EAS EMG activity upon vesical voiding, whereas a response was registered after saline administration. The increase of the rectal pressure and EAS EMG activity upon voiding suggests the presence of a reflex relationship between the two actions. This relationship is evidenced by reproducibility and by abolition of the response on anaesthetizing either of the proposed two arms of the reflex: the anorectum and the bladder. We call this reflex 'vesico-anorectal reflex'. The clinical significance of this vesico-anorectal reflex remains to be established.     

Internal anal sphincter relaxation associated with bisacodyl‐induced colonic high amplitude propagating contractions in children with constipation: a colo‐anal reflex?

Background Describe the association of internal anal sphincter (IAS) relaxation with colonic high‐ amplitude peristaltic contractions (HAPCs). Methods Retrospective review of colon manometry tracings of children with constipation to determine the IAS relaxation characteristics associated with HAPC’s (HAPC‐IASR) events and compare them to the those seen during the performance of the anorectal manometry (ARMRAIR) events. Key Results A total of 70 HAPC‐ IASRs were observed in 15 patients, 65 after bisacodyl, two during fasting and three after a meal. In 64% of events, the IAS relaxation started when the HAPC reached left colon and in 36% as proximal as the hepatic flexure. High‐ amplitude peristaltic contraction propagation seems to be important in HAPC‐IASR characteristics; those propagating distal to sigmoid colon demonstrated larger and longer IAS relaxation as well as lower residual pressure, but equivalent resting pressure compared with HAPC’s ending proximal to sigmoid colon. Although IAS resting pressure was comparable for ARM‐RAIRs and HAPC‐IASRs, the duration and magnitude of anal relaxation was higher, and the anal residual pressure was lower in HAPC‐IASRs. Conclusions & Inferences We demonstrated that IAS relaxation in constipated children is associated with HAPCs migrating in the proximal and distal colon; in most cases, starting when peristalsis is migrating through left colon and in an important proportion while migrating proximally. We also demonstrated that HAPC‐IASRs are different from ARM‐RAIRs suggesting a neurally mediated reflex. Finally, the IAS relaxation characteristics are highly dependent on the degree of propagation of HAPCs, which could have important implications in the understanding of defecation disorders.     

Tonic descending inhibition of the spinal cardio-sympathetic reflex in the cat

Electrical stimulation of the left inferior cardiac nerve elicited a two-component reflex potential (spinal and supraspinal reflexes) in the ipsilateral white ramus T3 from which recordings were made in chloralose-anaesthetised cats. Reversible interruption of all spinal pathways achieved by cooling the spinal cord at C2/C3 produced an enhancement of the spinal reflex and abolished the supraspinal reflex, the latter usually being the more prominent reflex potential prior to spinal cord block. The spinal cord block-induced increase in the amplitude of the spinal reflex was, however, less than the increase observed during stimulation of the somatic intercostal nerve T4. Recordings of the afferent volley following cardiac nerve stimulation and analysis of the stimulus-reflex response relationship in neuraxis-blocked cats indicated that the spinal reflex as determined here was activated by A delta afferent fibres. However, if stimulus strength was raised above C-fibre threshold, spinal cord block revealed in addition a late spinal reflex response. In some cases, the appearance of this late potential was accompanied by a secondary decline of the earlier spinal reflex potential, possibly indicating C-fibre-mediated afferent inhibition. Neither baroreceptor activation nor denervation had any effect on spinal reflex amplitudes. Pharmacologically, clonidine given i.v. to cats with a blocked neuraxis reduced the spinal reflex amplitudes to pre-block values, an action which could be antagonised by the subsequent administration of the alpha 2-adrenoceptor antagonist rauwolscine. When given to non-pretreated cats with intact neuraxis, however, neither rauwolscine nor its analog yohimbine were capable of inducing a persistent release from tonic inhibition. The results suggest that both purely visceral and somato-visceral reflexes are subject to tonic descending inhibition, but they do not support the hypothesis that a catecholamine is the responsible transmitter mediating this inhibition.     

The internal anal sphincter: regulation of smooth muscle tone and relaxation

Abstract  Basal tone in the internal anal sphincter (IAS) is primarily myogenic. Neurohumoral substances like angiotensin II may partially provide external signal for the basal tone in the IAS. The sphincteric relaxation on the contrary is neurogenic by activation of non-adrenergic non-cholinergic (NANC) nerves that release nitric oxide (NO), vasoactive intestinal polypeptide (VIP) and perhaps carbon monoxide. Because of the presence of spontaneous tone, the IAS offers an excellent model to investigate the nature of the inhibitory neurotransmission for NANC relaxation. Work from different laboratories in different species concludes that NO is the major contributor in the NANC relaxation. This may invoke the role of other inhibitory neurotransmitters such as VIP, working partly via NO. An understanding of the basic regulation of basal tone in the IAS and nature of inhibitory neurotransmission are critical in the pathophysiology and therapeutic potentials in the anorectal motility disorders.     

Electrophysiological investigation of beta, beta'-iminodipropionitrile neurotoxicity: monosynaptic reflexes and recurrent inhibition

beta-beta'-iminodipropionitrile (IDPN) neurotoxicity is morphologically characterized by the presence of giant axon swellings in the first proximal internodes of motor axons. The electrophysiological consequences of these proximal giant axon swellings on monosynaptic reflexes and recurrent inhibition were investigated along dorsal root-ventral root, medial gastrocnemius-ventral root and soleus-ventral root pathways of IDPN-intoxicated cats 35, 50 and 100 days following initial administration of the toxin (50 mg/kg/wk for 5 weeks). Monosynaptic reflex action potentials, normally relatively synchronous spike potentials, frequently appeared as doublet potentials which did not represent temporal fractionation of the spike potential. Latencies to the monosynaptic reflex action potentials were prolonged. Amplitudes of unconditioned monosynaptic reflex action potentials were significantly decreased at all time points, although there was a tendency for the amplitudes to recover with time. Post-tetanic potentiation was variously altered. Recurrent inhibition was reduced by 42-49% along monosynaptic reflex pathways. These results demonstrate that electrophysiological function in the spinal cord of IDPN-intoxicated cats is profoundly altered and the dysfunction partly results from the presence of the giant axon swellings.     

Differential effects of spinal 5-HT1A receptor activation and 5-HT2A/2C receptor desensitization by chronic haloperidol

The effects of 7- and 21-day haloperidol treatment on the spinal serotonergic system were examined in vivo in acutely spinalized adult rats. Intravenous administration of a selective 5-HT(2A/2C) receptor agonist, (+/-)-2,5-Dimethoxy-4-iodoamphetamine hydrochloride (0.1 mg/kg) significantly increased the excitability of spinal motoneurones as reflected by increased monosynaptic mass reflex amplitude. This was significantly reduced in rats treated with haloperidol (1 mg/kg/day, i.p.) for 7 and 21 days. Administration of a 5-HT(1A/7) receptor agonist, (+/-)-8-Hydroxy dipropylaminotetraline hydrobromide (0.1 mg/kg, i.v.) significantly inhibited the monosynaptic mass reflex. This inhibition was greatly prolonged in haloperidol treated animals. These results demonstrate that the effects of haloperidol on the activation and desensitization of 5-HT(1A) and 5-HT(2A/2C) receptors respectively, may be mediated via intracellular mechanisms shared by these receptors with dopamine D(2) receptors in the mammalian spinal cord. The above serotonergic mechanisms may be partly responsible for haloperidol-induced extrapyramidal motor dysfunction.     

Supraspinal regulation of spinal reflex discharge into cardiac sympathetic nerves

(1) In chloralose anaesthetized cats, reflex responses were recorded in inferior cardiac nerves following stimulation of intercostal nerves and hind limb afferent nerves. (2) In 80% of cats, a long latency reflex response alone was recorded, whereas, in the others, a short and long latency response was present to intercostal nerve stimulation. (3) In cats displaying only a long latency somatocardiac reflex response, damage to the ventral quadrant of the ipsilateral cervical spinal cord, through which runs a bulbospinal inhibitory pathway, resulted in the appearance of shorter latency reflexes to intercostal nerve stimulation. Lesions elsewhere in the cervical cord did not do this. (4) The characteristics of the early responses indicated that they were somatosympathetic reflexes and not dorsal root reflexes. (5) The early reflexes remained and the late reflex disappeared on subsequent complete transection of the spinal cord. The early reflexes were therefore spinal reflexes, and suppressed in the animal with cord intact. (6) Lesions at C4, which included a contralateral hemisection and a section of dorsal columns extending into the dorsal part of the lateral funiculus, abolished the inhibition of a sympathetic reflex that followed stimulation of some somatic afferent nerve fibres. These sections did not release the spinal reflex. Therefore, this reflex inhibition was not responsible for the suppression of the spinal somatosympathetic reflex. (7) The descending inhibitory influence on the segmental reflex pathway was not antagonized by strychnine, bicuculline or picrotoxin. (8) The possibility is discussed that the spinal reflex pathway into cardiac sympathetic nerves is tonically inhibited by a bulbospinal pathway originating from the classical depressor region of the ventromedial reticular formation.     

Basal internal anal sphincter tone,inhibitory neurotransmission,and other factors contributing to the maintenance of high pressures in the anal canal

Maintenance of the basal tone in the internal anal sphincter (IAS) is critical for rectoanal continence. Effective evacuation requires a fully functional rectoanal inhibitory reflex (RAIR)‐mediated relaxation of the IAS via inhibitory neurotransmission (INT). Systematic studies examining the nature of the INT in different species have identified nitric oxide (NO) as the major inhibitory neurotransmitter. However, other mediators such as vasoactive intestinal polypeptide (VIP), ATP, and carbon monoxide (CO) may also play species‐specific role under certain experimental conditions. Measurements of the intraluminal pressures in the IAS along with the force of the isolated IAS tissues are the mainstay in the basic studies for the molecular mechanisms underlying the basal tone and in the nature of the INT. The identification of NO as the inhibitory neurotransmitter has led to major advances in the diagnosis and treatment of a number of rectoanal motility disorders associated with the IAS dysfunction. Besides the IAS, the high pressures in the anal canal are affected by the external anal sphincter (EAS) function, and its malfunction may also lead to rectoanal incontinence. Different approaches including biofeedback have been attempted to improve the EAS function, with variable outcomes. There is a dire need for the innovative ways to improve the week high pressures zone in the anal canal. This viewpoint focuses on two studies that extend the above concept of multiplicity of inhibitory neurotransmitters ( Neurogastroenterol Motil 2011 23 e11–25 ), and that high pressures in the anal canal can be improved by the EAS plication ( Neurogastroenterol Motil 2011 23 70–5 ).     

Effects of catecholamines on spinal motoneurones and spinal reflex discharges in the isolated spinal cord of the newborn rat

The effects of catecholamines on spinal motoneurones and spinal reflex discharges were investigated in the isolated spinal cord of newborn rat. Noradrenaline (NA), adrenaline (Adr), dopamine (DA) and isoproterenol (Iso) caused depolarization of the motoneurones in a dose-dependent manner. The depolarizing action persisted in Ca2+-deficient Krebs solution. The order of potency was Adr greater than NA greater than DA much greater than Iso. The effects of NA and Adr on the monosynaptic reflex discharge varied; depression, potentiation or depression followed by potentiation. The polysynaptic reflex discharge was consistently depressed. DA depressed both the mono- and polysynaptic reflex discharges in all the preparations. Tyramine and adamantanamine induced a response similar to that to DA rather than to NA. Depolarization of the motoneurones and the effects on the spinal reflex discharges induced by all the catecholamines were decreased by phentolamine or phenoxybenzamine but not by propranolol or haloperidol. It is suggested that the endogenous catecholamines, mainly DA, depolarize the motoneurones and depress the mono- and polysynaptic reflex discharges through an alpha-adrenoceptor in the spinal cord of the newborn rat.     

Late flexion reflex in paraplegic patients. Evidence for a spinal stepping generator

We demonstrated previously that electrical stimulation of the Flexor Reflex Afferents (FRA) induces a late flexion reflex with a central conduction time longer than 100 msec. Its latency is prolonged by increasing the intensity or the duration of the stimulation. This late reflex is therefore similar to the late flexion reflex observed in acute spinal cat with DOPA. Some findings suggest that in man the late flexion reflex could be inhibited at a premotoneuronal level by contralateral FRA stimulation. In relation to the late flexion reflex, a late contralateral facilitation of soleus monosynaptic reflex (MSR) was observed. Rhythmical activity was observed in only one patient who had an exceptional form of spinal myoclonus. This myoclonus could be modulated by FRA stimulation. These facts show that the reflex organization in paraplegic patients is similar to the one described in acute spinal cat with DOPA and therefore suggest that a spinal stepping generator could exist in humans.     

The postnatal reorganization of primary afferent input and dorsal horn cell receptive fields in the rat spinal cord is an activity-dependent process

The dorsal horn of the spinal cord in the newborn rat is characterized by large cutaneous mechanoreceptive fields, a predominance of A‐fibre synaptic inputs and diffuse primary afferent A‐fibre projections, all of which are gradually reduced and refined over the first postnatal weeks. This may be partly responsible for the reduction in cutaneous flexion reflex sensitivity of rats over the postnatal period. Here we show that chronic, local exposure of the dorsal horn of the lumbar spinal cord to the NMDA antagonist MK801 from birth prevents the normal functional and structural reorganization of A‐fibre connections. Dorsal horn cells in spinal MK801‐treated animals, investigated at eight weeks of age by in vivo electrophysiological recording, had significantly larger cutaneous mechanoreceptive fields and greater A‐fibre evoked responses than vehicle controls. C‐fibre evoked responses were unaffected. Chronic MK801 also prevented the normal structural reorganization of A‐fibre terminals in the spinal cord. The postnatal withdrawal of superficially projecting A‐fibre primary afferents to deeper laminae did not occur in treated animals although C‐fibre afferent terminals and cell density in the dorsal horn were apparently unaffected. Spinal MK801‐treated animals also had significantly reduced behavioural reflex thresholds to mechanical stimulation of the hindpaw compared to naïve and vehicle‐treated animals, whereas noxious heat thresholds remained unaffected. The results indicate that the normal postnatal structural and functional development of A‐fibre sensory connectivity within the spinal cord is an activity‐dependent process requiring NMDA receptor activation.     

Analysis of reflex activity in cardiac sympathetic nerve induced by myelinated phrenic nerve afferents

Electrical stimulation of the phrenic nerve afferents evoked excitatory responses in the right inferior cardiac sympathetic nerve in chloralose-anaesthetized cats. The reflex was recorded in intact and spinal cats. The latency and threshold of the volley recorded from the phrenic nerve as well as of the cord dorsum potentials evoked by electrical stimulation of the phrenic nerve indicated that group III afferents were responsible for this reflex. The phrenicocardiac sympathetic reflex recorded in intact cats was followed by a silent period. The maximum amplitude of the reflex discharges was 800 microV, the latency was 83 ms and the central transmission time 53 ms. Duration of the silent period lasted up to 0.83 s. In spinal cats the reflex was recorded 5.5-8 h after spinalization. The maximum amplitude of the spinal reflex discharges ranged from 22 to 91 microV and the latency from 36 to 66 ms.     

N-methyl-D-aspartate antagonist applied to the spinal cord hindlimb enlargement reduces the amplitude of flexion reflex in the turtle

APV (D(-)-2-amino-5-phosphonovalerate), an NMDA (N-methyl-D-aspartate) antagonist, was applied in situ onto segments of the hindlimb enlargement of the turtle spinal cord. APV reduced the response amplitude of the flexion reflex. In contrast, APV did not alter the responsiveness of the rostral scratch reflex. Afferents for the flexion reflex enter the spinal cord via the dorsal roots of the middle segment of the hindlimb enlargement; afferents for the rostral scratch reflex enter the spinal cord via dorsal roots located anterior to the hindlimb enlargement. The results are consistent with the hypothesis that sensory interneuron NMDA receptors, synaptically activated either directly or indirectly by nearby cutaneous afferent axons, play a role in the spinal cord processing of cutaneous information.     

Identification of spinal neurons involved in the urethrogenital reflex in the female rat

The urethrogenital (UG) reflex is a spinal sexual reflex that consists of autonomic and somatic nerve activity and vaginal, uterine, and anal sphincter contractions. The UG reflex is under tonic descending inhibition by neurons in the region of the nucleus paragigantocellularis (nPGi). The location of spinal neurons activated by the UG reflex was examined in the female rat using the immediate early gene, c-fos. In addition, the descending inputs from the nPGi onto fos-activated neurons was examined using the anterograde tracer biotin dextran amine injected into the nPGi. The UG reflex resulted in a significant increase in fos-positive nuclei in segments T12-S1, compared with experimental controls in which the UG reflex was not activated. Spinal circuits involved in the UG reflex include neurons relaying afferent information from the pudendal sensory nerve, in the dorsal horn and medial cord of L5-S1. Efferent output includes preganglionic neurons located in the lateral gray of L5-S1 and lateral and medial gray of T13-L2. Spinal interneurons involved in the UG reflex were found close to the preganglionic neurons and in the dorsal horn and intermediate and medial gray of T12-S1. NPGi inputs were found primarily on the autonomic efferents and interneurons in the medial and intermediate gray. These studies demonstrate multisegmental spinal circuits activated with the UG reflex and demonstrate that the descending inhibition from the nPGi is by means of preganglionic and somatic efferents and spinal interneurons closely associated with the efferent output.     

Spinal reflexes and the concentrations of 5-HIAA, MHPG, and HVA in lumbar cereborspinal fluid after spinal lesions in man.

Descending bulbospinal pathways that employ specific neurotransmitter substances are known to be capable of modulating segmental reflex activity in the experimental animal. To determine whether this might also occur in man correlations have been sought between the activity in spinal reflex pathways and the lumbar cerebrospinal fluid (CSF) concentrations of 5-hydroxyindolacetic acid (5-HIAA), 3 methoxy-4-hydroxyphenylglycol (MHPG), and homovanillic acid (HVA) in 12 patients with complete or virtually complete spinal lesions. The concentrations of 5-HIAA and MHPG in lumbar CSF ARE REDUCED AFTER COMPLETE OR VIRTUALLY COMPLETE SPINAL LESIONS IN MAN. This may occur within 18 days of the lesion. MHPG concentrations appear to be inversely related to the level of the lesion. The HVA concentration in lumbar CSF is reduced when there is obstruction of the CSF pathways. No relationship could be demonstrated between the concentrations of 5-HIAA or MHPG in lumbar CSF and the activity in the spinal monosynaptic pathway (estimated from the proportion of the motoneurone pool activated by the Achilles tendon reflex or H reflex) or the activity of a spinal inhibitory mechanism (estimated by the degree of vibratory inhibition of the monosynaptic reflex). Patients with a tonic vibration reflex (TVR) tended to have higher MHPG levels. There appeared to be an association between low CSF HVA and enhanced vibratory inhibition of the monosynaptic reflex in the nine patients whose spinal lesions were complete.