Developmental tuning in a spinal nociceptive system: effects of neonatal spinalization.

Recent studies indicate a modular organization of the nociceptive withdrawal reflex system. Each module has a characteristic receptive field, closely matching the withdrawal movement caused by its effector muscle. In the rat, the strength of the sensory input to each module is tuned during the first postnatal weeks, i.e., erroneous spinal connections are depressed, and adequate connections are strengthened. To clarify if this tuning is dependent on supraspinal structures, the effect of a complete neonatal spinal cord transection on the postnatal tuning of withdrawal reflexes was studied. The nociceptive receptive fields of single hindlimb muscles and compound withdrawal reflexes were examined in decerebrate unanesthetized and awake rats, respectively. Noxious thermal CO(2) laser stimulation was used to evoke reflex responses. Neonatal spinal cord transection resulted in a disrupted reflex organization in the adult rat, resembling that previously found in neonatal rats. The receptive fields of single hindlimb muscles exhibited abnormal distribution of sensitivity not matching the withdrawal action of the effector muscles. Likewise, the composite nocifensive movements, as documented in the awake rat, often resulted in erroneous movements toward the stimulus. It is concluded that withdrawal reflexes do not become functionally adapted in rats spinalized at birth. These findings suggest a critical role for supraspinal systems in the postnatal tuning of spinal nociceptive systems.     

Modular organization of excitatory and inhibitory reflex receptive fields elicited by electrical stimulation of the foot sole in man.

OBJECTIVES: The present study aimed to investigate how the inhibitory and excitatory reflex components of the human (polysynaptic) withdrawal reflex are organized depending on the stimulation site. The reflexes were elicited during a voluntary pre-contraction (between 10 and 20% of maximum voluntary contraction) of two antagonistic muscles. METHODS: Inhibitory and excitatory reflex receptive fields to tibialis anterior (TA) and soleus (SO) were mapped in 14 healthy subjects using randomized electrical stimulation at 16 sites of the foot sole. Low, non-painful (3x perception threshold), and high, painful (1.5x pain threshold), stimulus intensities were used. RESULTS: The inhibitory reflex receptive fields were organized in a highly functional manner supporting the action of the excitatory reflex. Together the two reflexes result in an optimal withdrawal from the stimulus. Low stimulation intensity was found sufficient to elicit the inhibitory reflex. High stimulation intensity caused a reversal of the inhibition to excitation in tibialis anterior. In soleus the inhibition was facilitated for stronger intensities. CONCLUSION: In conclusion, findings in animals of a modular organization of inhibitory reflexes are reproduced in humans.     

Distal hind-limb reflex responses in cats with largely intact spinal reflex circuits

Reflex responses to single shocks to peripheral nerves were studied in the small muscles of the hind limb of the decerebrated and subsequently spinalized cat. Monosynaptic and high threshold polysynaptic reflexes of plantar muscles evoked by tibial nerve shocks were significantly more active in preparations that had extensive dissection of nerves and muscles. Monosynaptic reflexes were more active in the plantar flexor portion than in other parts of the interosseus. Compared with proximal limb muscles, this muscle showed features of reflex behavior that were neither consistently flexor nor extensor. In spinal animals the threshold of the tibialis anterior to tibial nerve shocks was often less than the threshold for other muscles, suggesting a function other than nociceptive flexion reflex, probably tactile influence in gait. Extensor digitorum brevis reflexes did not exhibit the flexor reflex pattern typified by those of the tibialis anterior muscle. The data further suggest activation of these reflexes by Ib interosseus muscle afferents and plantar cutaneous afferents and tonic inhibition from Ia receptors.     

Modulation of spinal inhibitory reflex responses to cutaneous nociceptive stimuli during upper limb movement

In the present study we investigated the probability, latency and duration of the inhibitory component of the withdrawal reflex elicited by painful electrical stimulation of the index finger in humans. The stimulus consisted of a train of high-intensity pulses. The investigation was carried out in several upper limb muscles during isometric contractions of different strengths and during a motor sequence consisting of reaching, picking up and transporting an object. We used a new algorithm to detect and characterize the inhibitory reflex. The reflex was found in all muscles except the brachioradialis at all the isometric contraction strengths, and showed a distal-to-proximal gradient of latency and duration. Conversely, during movement the reflex probability was high (> 80%) in the anterior deltoid and triceps muscles during reaching, in the extensor carpi radialis muscle during transporting of the object, and in the first interosseous muscle during both picking up and transporting of the object. This modulation of inhibitory reflex transmission in the upper limb muscles suggests that the motor response is organized in such a way as to inhibit the overall ongoing motor task by interrupting motion during reaching and by releasing the object during transporting. This pattern of modulation appears to differ markedly from that previously reported for the excitatory component of the withdrawal reflex. Study of the nociceptive inhibitory reflexes during movement offers new and more profound insights into the functional anatomical organization of the spinal interneuronal network mediating sensory–motor integration.     

Modulating effects of bodyweight unloading on the lower limb nociceptive withdrawal reflex during symmetrical stance

ObjectiveTo investigate the effects of bodyweight unloading on the excitability of the nociceptive withdrawal reflex (NWR) and of its receptive fields organisation during quiet stance in humans.MethodsThe NWR was elicited in 14 volunteers by electrical stimulation of the sole of the foot at mid-forefoot, arch, and heel points. Participants stood upright and wore a whole-body harness connected via a rope to a pulley. Data were recorded at 0%, 10%, 25% and 40% of the bodyweight unloading. The root mean square of the EMG activity was measured bilaterally from several lower limb muscles. Kinematics of ankle, knee, and hip were measured bilaterally using goniometers.ResultsTwo-way ANOVA for repeated measures revealed higher reflex sizes at higher degrees of unloading in the tibialis anterior, soleus, and biceps femoris muscles and in the kinematics of the knee joint of the ipsilateral limb. No interaction between stimulation site and unloading was revealed.ConclusionsUnloading induced a generalised enhancement of NWR excitability without modifying the reflex receptive field organisation.SignificanceOur study indicates that bodyweight unloading in general enhances the NWR excitability and suggests that only load-related afferent inputs in concert with joint movements may modify the modular organisation of the NWR.     

Distribution of Cutaneous Nociceptive and Tactile Climbing Fibre Input to Sagittal Zones in Cat Cerebellar Anterior Lobe

Climbing fibres projecting to the cerebellar C3 zone (and the related C1 and Y zones) receive spatially well organized tactile and nociceptive inputs from the skin. In the present study, cutaneous tactile and nociceptive input to climbing fibres projecting to the X, B, C2 and D1 zones in lobule V were investigated in pentobarbitone-anaesthetized cats. From the present results and previous studies, it is concluded that the X, C1, CX, C3 and Y zones receive cutaneous nociceptive climbing fibre input. By contrast, climbing fibres to the B, C2 and D1 zones lack cutaneous nociceptive input. Tactile input was found in all zones. The spatial organization of receptive fields of climbing fibres projecting to the X and D1 zones was similar to that in the C3 zone. They were located on the ipsilateral forelimb, mainly its lateral and distal parts, and their proximal borders were located close to joints. In the B zone, more than half of the receptive fields of climbing fibres were confined to the ipsilateral hind- or forelimb. However, frequently more than one limb and parts of the trunk were included. In the C2 zone, the majority of climbing fibres had distal ipsi- or bilateral receptive fields on the forelimbs, often also including the head/face. Some of the bilateral forelimb receptive fields additionally included the hindlimbs ipsi- or bilaterally. The results indicate that each zone has a characteristic set of climbing fibre receptive fields, which is probably related to its efferent control functions.     

Relation Between Cutaneous Receptive Fields and Muscle Afferent Input to Climbing Fibres Projecting to the Cerebellar C3 Zone in the Cat

Inferior olivary cells projecting as climbing fibres to the forelimb area of the cerebellar C3 zone were investigated with respect to their cutaneous and muscle afferent input in barbiturate-anaesthetized cats. Climbing fibre responses were recorded from single cerebellar cortical Purkinje cells on natural stimulation of the skin and on electrical stimulation of nerves to m. biceps brachii, m. triceps brachii and to nine muscles acting as dorsal or palmar flexors of the paw (and, in some cases, the digits). The analysis was focused on the functional organization of convergence between cutaneous and muscle afferents onto single olivary neurons. Cutaneous receptive fields on the dorsal side of the paw and on the digits were generally associated with moderate to strong input from dorsal flexors, but little or no input from palmar flexors or proximal muscles. Receptive fields on the ventral side of the paw and forearm were associated with relatively strong input from biceps and palmar flexors. Climbing fibres with cutaneous receptive fields extending on the ulnar side of the paw and forearm usually received strong input from the triceps and moderate to strong input from dorsal flexors, whereas input from the palmar flexors was weak or lacking. In conclusion, the results indicate that the cutaneous receptive fields in many cases are associated with input from muscles the action of which would tend to move the receptive field towards a stimulus applied to the skin.     

Responses of neurons in nucleus ventralis posterolateralis of the cat thalamus' to hypogastric inputs

Recordings were made from 68 units in the nucleus ventralis posterolateralis (VPL) of the cat thalamus, which responded to stimulation of hypogastric afferents. These units also received nociceptive inputs from the contralateral integument. Units which responded exclusively to hypogastric afferent inputs were not found. Thirty seven of the units were nociceptive specific (NS), and the remaining 31 were wide dynamic range (WDR) units. All of these units were located in the shell region of the lateral subdivision of the caudal VPL. NS units responding to hypogastric afferent inputs had a circumscribed cutaneous receptive field on the contralateral abdomen, gluteal region, tail or hind limb. These areas corresponded to tactile dermatomes T13-S2. Similarly, the cutaneous receptive fields of WDR units receiving hypogastric afferent inputs were distributed in the contralateral abdomen, gluteal region, tail and hind limb, with the sole exception of one unit, whose receptive field also included a part of the lower thorax. These findings extend the previous findings that the shell region of the caudal VPL of the cat thalamus constitutes a thalamic link in a visceral pain pathway, and that the visceral and cutaneous pathways share a common projection locus in the VPL.     

The palmo-mental reflex. An electrophysiological study.

Repeated electric stimulation of the ulnar nerve fibers was applied at the wrist in 7 normal and 32 pathological subjects; the response reflexes were simultaneously recorded in the chin muscles and at the upper limb, on the flexor carpi ulnaris. Although it is possible to obtain two distinct polysynaptic reflexes by cutaneous stimulation of the limb, the palmo-mental reflex causes a unique response, the latency of which may diminish to 35 msec. This response occurs most often at the threshold which elicits a nociceptive reflex of the upper limb. The palmo-mental reflex is almost always bilateral for a unilateral stimulation and in numerous instances is characterized by a wide receptive field. These findings suggest that the palmo-mental reflex is an early event in a general nociceptive response. In the normal subject this fragment of a general response to a painful stimulus is highly suppressed as are the local reflexes by suprasegmental control. The palmo-mental reflex is liberated and augmented in the event of habitually bilateral lesions of the pyramidal tract or the extra-pyramidal formations.     

Modular organization of human leg withdrawal reflexes elicited by electrical stimulation of the foot sole.

Human withdrawal reflex receptive fields were determined for leg muscles by randomized, electrical stimulation at 16 different positions on the foot sole. Tibialis anterior, gastrocnemius medialis, peroneus longus, soleus, rectus femoris, and biceps femoris reflexes, and ankle joint angle changes were recorded from 14 subjects in sitting position. Tibialis anterior reflexes were evoked at the medial, distal foot and correlated well with ankle dorsal flexion. Gastrocnemius medialis reflexes were evoked on the heel and correlated with plantar flexion. Stimulation on the distal, medial sole resulted in inversion (correlated best with tibialis anterior activity), whereas stimulation of the distal, lateral sole evoked eversion. Biceps femoris reflexes were evoked on the entire sole followed by a small reflex in rectus femoris. A detailed withdrawal reflex organization, in which each lower leg muscle has its own receptive field, may explain the ankle joint responses. The thigh activity consisted primarily of flexor activation.     

The effect of neonatal testosterone on specific male and female patterns of phosphorylated cytosolic proteins in the rat preoptic-hypothalamus, cortex and amygdala

The original evidence that spared cutaneous nerves will sprout following partial denervation of skin was obtained in adult rabbits, in which nociceptive function returned to the deprived areas. Recently we reported that in the adult rat intact touch-sensitive (low-threshold mechanosensory) nerves fail to establish new functional endings in adjacent denervated skin. We have now investigated low-threshold mechanosensory nerves in the skin of adult rabbits after partially denervating the ear or hind limb; the sprouting of new functional endings into neighboring skin would be revealed by an expansion of the low-threshold receptive fields of cutaneous nerves (the areas of skin from which impulses could be evoked by stroking with a bristle). The results show that intact low-threshold mechanosensory nerves do not establish functional endings in adjacent denervated skin in the adult rabbit. These findings, together with those now reported for the cat as well as the rat, support the conclusion that possibly in all adult mammals intact low- and high-threshold nerves differ in their ability to respond to the presence of adjacent denervated skin by sprouting.     

Spinal reflex pattern to foot nociceptive stimulation in standing humans

Ipsi- and contralateral patterns of lower limb nociceptive reflex responses were studied in 6 normal subjects in free standing position. Once the position was stabilized, only ankle extensor muscles showed consistent tonic activity while ankle flexors and knee extensors and flexors were virtually silent. Reflex responses, elicited by painful electrical stimuli to the skin of the plantar and dorsal aspect of the foot, were recorded from ipsi- and contralateral quadriceps (Q), biceps femoris (Bic), tibialis anterior (TA) and soleus (Sol) muscles. Plantar foot stimulation evoked a large excitatory response in the ipsilateral TA at about 80 ms and a smaller responses in Bic and Q at 70 ms and 110 ms, respectively. Ipsilateral excitatory effects after dorsal foot stimulation consisted of a Bic response at about 75 ms. In addition to excitatory effects, both plantar and dorsal foot stimulation evoked long-lasting suppression of ipsilateral Sol background activity starting at about 60 ms. Contralaterally, the only nociceptive effects after plantar or dorsal foot stimulation were a small excitatory response of Sol at about 85 ms. Evidence is provided that only excitatory responses were contingent upon nociceptive volley. The main mechanical effects seen after plantar stimulation were dorsiflexion of the foot without loss of heel contact with the floor; no withdrawal response of the foot followed nociceptive dorsal stimulation. Our main conclusion is that only reflex nociceptive responses serving to avoid the stimulus without conflicting with limb support function are expressed. The mechanisms reconciling nociceptive action and postural function of the lower limbs are discussed.     

Ipsi- and contralateral exteroceptive EMG modulation in uni- and bilaterally activated thenar muscles.

OBJECTIVE: The cutaneous silent period (CSP) is a spinal inhibitory reflex mediated by A-delta fibers. The exact underlying neural pathway, however, is unknown. This study was undertaken to investigate whether the neural circuitry mediating CSPs is wired unilaterally or whether there is evidence of influence from or upon the contralateral side. METHODS: Fifteen healthy subjects underwent bilateral CSP testing following unilateral nociceptive digit II stimulation. Surface electromyographic (EMG) recordings were obtained bilaterally from thenar muscles following unilateral recurrent nociceptive digit II stimulation while activating the ipsilateral or the contralateral or both thenar muscles against resistance. RESULTS: Nociceptive digit II stimulation evoked consistent CSPs in ipsilateral thenar muscles during voluntary contraction, while there was no consistent influence on EMG activity in contralateral thenar muscles at rest. Furthermore, nociceptive digit II stimulation did neither consistently affect EMG activity in ipsilateral thenar muscles at rest nor in contralateral thenar muscles during voluntary contraction. Finally, there was no significant difference between any CSP parameters obtained during unilateral versus bilateral muscle contraction. Occasional late excitatory EMG activity in relaxed or contracted thenar muscles resembled startle reflexes, which seem to contribute to the post-inhibition EMG-rebound. CONCLUSIONS: The present findings are consistent with unilateral wiring of the spinal circuitry mediating CSPs. SIGNIFICANCE: The essential lack of a crossed inhibitory influence of nociceptive digit II stimulation underscores the utility of CSP testing in the assessment of the A-delta fiber system in healthy subjects and patients with various pathologies.     

Somatotopic organization of the dorsal horn in the lumbosacral enlargement of the spinal cord in the neonatal cat

The somatotopic organization of the light touch receptive fields of single unidentified dorsal horn neurons in the lumbosacral spinal cord has been studied in the neonatal cat anesthetized with chloralose. Satisfactory recordings were obtained from single dorsal horn neurons in kittens aged 3-6 days. Reconstruction of recording tracks from pontamine blue dye spots and comparisons of the depths of recording sites with Nissl-stained sections of cord showed that most single-unit recordings were obtained from laminae III and IV of Rexed. In animals of all ages neurons were found which responded briskly to light cutaneous mechanical stimulation. Their receptive fields varied widely in size, being smallest on the distal digits and largest on proximal skin. Receptive field areas were similar in proportion to the size of the hindlimb to those seen in the equivalent region in the adult cat. Because of the shape of the dorsal horn and the relatively narrow dorsal columns in neonatal kittens it proved difficult to locate units with receptive fields on proximal skin. Nevertheless the main features of the somatotopic organization of the dorsal horn were similar to those in the adult cat. Thus the somatotopic map of the kitten showed a medial representation of glabrous skin that was bounded laterally by the representation of the hairy skin of the toes. Proximal skin was represented in the lateral parts of the dorsal horn, a region which was not easily accessible for microelectrode recording. The individual toes were represented in a rostral to caudal sequence such that toe 2 was represented rostrally and toe 5 caudally. Around the toe representation the medial surface of the foot was represented rostrally, the ventrolateral surface caudally, and the dorsal surface laterally. The results indicate that the mature organization of light touch receptive fields of dorsal horn neurons in the lumbosacral cord of the cat is already largely present at birth.     

Gradual enlargement of human withdrawal reflex receptive fields following repetitive painful stimulation

Dynamic changes in the topography of the human withdrawal reflex receptive fields (RRF) were assessed by repetitive painful stimuli in 15 healthy subjects. A train of five electrical stimuli was delivered at a frequency of 3 Hz (total train duration 1.33 s). The train was delivered in random order to 10 electrode sites on the sole of the foot. Reflexes were recorded from tibialis anterior, soleus, vastus lateralis, biceps femoris, and iliopsoas (IL). The RRF changes during the stimulus train were assessed during standing with even support on both legs and while seated. The degree of temporal summation was depending on stimulation site. At the most sensitive part of the RRF, a statistically significant increase in reflex size was seen after two stimuli while four stimuli were needed to observe reflex facilitation at less sensitive electrode sites. Hence, the region from which reflexes could be evoked using the same stimulus intensity became larger through the train, that is, the RRF was gradually expanding. Reflexes evoked by stimuli four and five were of the same size. No reflex facilitation was seen at other stimulus sites outside the RRF. In all muscles except in IL, the largest reflexes were evoked when the subjects were standing. In the ankle joint, the main withdrawal pattern consisted of plantar flexion and inversion when the subjects were standing while dorsi-flexion was prevalent in the sitting position. Up to 35 degrees of knee and hip flexion were evoked often leading to a lift of the foot from the floor during standing. In conclusion, a gradual expansion of the RRF was seen in all muscles during the stimulus train. Furthermore, the motor programme task controls the reflex sensitivity within the reflex receptive field and, hence, the sensitivity of the temporal summation mechanism.     

Differential Effects of a Distant Noxious Stimulus on Hindlimb Nociceptive Withdrawal Reflexes in the Rat

Recent studies indicate that the nociceptive withdrawal reflexes to individual muscles are evoked by separate reflex pathways. The present study examines whether nociceptive withdrawal reflexes to different muscles are subject to differential supraspinal control in rats. A distant noxious stimulus was used to activate a bulbospinal system which selectively inhibits 'multireceptive' neurons (i.e. neurons receiving excitatory tactile and nociceptive inputs) in the dorsal horn of the spinal cord. Withdrawal reflexes, recorded with electromyographic techniques in single hindlimb muscles, were evoked by standardized noxious pinch. Thirty-seven rats, anaesthetized with halothane and nitrous oxide, were used. Whereas withdrawal reflexes to the extensor digitorum longus and brevis, tibialis anterior and biceps posterior muscles were strongly inhibited, reflexes to interossei muscles were potentiated during noxious pinch of the nose. Reflexes to peronei muscles were not significantly changed. The effects on the reflexes usually had an onset latency of <0.5 s and outlasted the conditioning stimulation by up to 2 s. The monosynaptic la reflex to the deep peroneal nerve, innervating dorsiflexors of the digits and ankle, was not significantly changed during noxious pinch of the nose. Hence, the inhibitory effects on the hindlimb withdrawal reflexes induced by the conditioning stimulation were presumably exerted on reflex interneurons. It is concluded that nociceptive withdrawal reflexes to different hindlimb muscles are differentially controlled by descending pathways activated by a distant noxious stimulus. The results support our previous conclusion that there are separate nociceptive withdrawal reflex pathways to different hindlimb muscles.     

Spatial facilitation of motor evoked responses in monitoring during spinal surgery.

During spinal cord monitoring, motor responses in the tibialis anterior muscles were recorded on transcranial electrical stimulation of the motor cortex. In order to facilitate the responses, the cortical stimulus was preceded by a train of stimuli to the foot sole within the receptive field of the withdrawal reflex of the tibialis anterior muscle. This cutaneous input provides a spatial facilitation of the cortically elicited response. When the stimulus interval was 50-100 ms, large and reliable responses were seen in most cases.     

Functional significance of projection from the cerebellar nuclei to the motor cortex in the cat.

The functional organization of projections from the cerebellar subcortical nuclei to the motor cortex through the nucleus ventralis lateralis (VL) of the thalamus was studied using tungsten microelectrodes for stimulation and recordings in acute and chronic cats. The following results were obtained. (1) Microstimulation of a small area of the ventral thalamus produced contraction of a single limb muscle as well as movements of whiskers. (2) The stimulus parameters for producing low threshold contraction of limb muscles were different from those for face muscles. The decrease of the frequency gradualy increased the threshold values for face muscles whereas the decrease abruptly increased the threshold for limb muscles. The optimum duration of the train for the lowest thresholds was longer for face muscles. (3) Stimulation of cerebellar nuclei (interpositus and lateralis) produced contraction of limb muscles. The stimulus parameters for the minimum threshold were similar to those for producing contraction of limb muscles from the ventral thalamus. (4) The peripheral receptive fields of neurons located around the low threshold sites in the thalamus were diffuse, i.e. they were driven insecurely by twisting the joints or pressure to the deep structures, but could not be driven by touch or light pressure on a circumscribed area of the body. (5) Chronic ablation of the motor cortex did not abolish the muscle contractions produced by thalamic stimulation, excluding the possibility that the effects were produced by stimulation of the branches of the pyramidal tract fibers reaching the ventral thalamus. (6) Chronic section of the brachium conjunctivum abolished or changed the characteristics of the contractions produced by thalamic stimulation indicating that the previous effects were produced by stimulation of cerebellar efferent fibers reaching the thalamus. (7) From these results it was concluded that the efferent impulses originating from the cerebellar nuclei can produce contraction of a particular muscle through activation of the red nucleus. These impulses are, at the same time, transmitted to a small group of neurons in the VL and then forwarded to the neurons in the motor cortex. (8) The functional significance of the VL projection system has been discussed in relation to the efferent zones within the motor cortex.     

Reflex receptive fields for human withdrawal reflexes elicited by non-painful and painful electrical stimulation of the foot sole.

OBJECTIVES: Human withdrawal reflex receptive fields (RRFs) were assessed for 4 different electrical stimulus intensities, ranging from below the pain threshold (PTh) to up to two times the PTh intensity (0.8x, 1.2x, 1.6x, and 2.0xPTh). METHODS: Thirteen subjects participated, and the reflexes were recorded in a sitting position. The stimuli were delivered in random order to 12 positions distributed over the foot sole. Tibialis anterior (TA), gastrocnemius medialis (GM), vastus lateralis (VL), and biceps femoris (BF) reflexes were recorded. Further, knee and ankle joint angle changes were recorded. RESULTS: The strongest reflexes were seen in the TA compared with the other 3 muscles. Dorsi-flexion dominated distal to the talocrural joint corresponding to the TA receptive field area. An expansion of the RRF for the TA and GM was seen when increasing the stimulus intensity from 0.8xPTh to 1.2xPTh and from 1.2xPTh to 1.6xPTh, indicating a gradually increasing reflex threshold towards the border, where TA contraction is inappropriate in a withdrawal reaction. For the BF and VL, the borders of the RRF areas were not detected. By integrating the reflex size within the RRF (i.e. the reflex volume), gradually increasing reflexes for increasing stimulus intensity were seen in all 4 muscles tested, most clearly in the TA and GM. The subjective pain intensity correlated to the reflex volume for the TA, GM, and BF. CONCLUSIONS: In conclusion, the highest reflex sensitivity was seen in the centre of the RRF, while the stimulus intensity needed for eliciting a reflex increased towards the receptive field border. Within the RRF, stronger reflexes were evoked for increasing stimulus intensity. The limit in the size of the receptive field size for the TA and GM supports a modular withdrawal reflex organisation.     

Cutaneous vascular responses evoked by noxious stimulation in rats with the spinal nerve ligation-induced model of neuropathy

Antidromic activation of nociceptive nerve fibres innervating the skin produces an axon reflex that involves extravasation and vasodilation of cutaneous blood vessels. We determined whether the axon reflex of the hindlimb skin is influenced by an experimental model of neuropathy induced by unilateral ligation of spinal nerves L(5) and L(6) in the rat. Ligation of spinal nerves induced symptoms mimicking tactile allodynia, as indicated by a marked decrease of the hindlimb withdrawal threshold to mechanical stimulation. The axon reflex induced by antidromic electrical stimulation of nociceptive fibres innervating the plantar skin ipsilateral to the ligation was attenuated according to determination of extravasation response and blood flow response. Lidocaine block or transection of the sciatic nerve of the neuropathic limb did not induce any change in basal blood flow of the plantar skin. The results indicate that ligation of spinal nerves induces an attenuation of the axon reflex. This attenuation reflects a decrease in the efferent function of primary afferent nociceptors innervating the hypersensitive skin of the hindpaw. The attenuation of antidromically-induced vascular responses was not caused by overriding sympathetic activity, as indicated by lack of blood flow effects by lidocaine blocks or a transection of the sciatic nerve.