Heat-sensitive conduction block in ulnar neuropathy at the elbow.

OBJECTIVES: To study the effects of elbow heating on conduction block (CB) and across-elbow conduction velocity (CV) in patients with ulnar neuropathy at the elbow (UNE). METHODS: We studied 15 patients with UNE, performing motor nerve conduction studies at 32 degrees C and after heating the elbow to 42 degrees C. RESULTS: At 32 degrees C, mean response amplitude and area with above-elbow (AE) stimulation were 20.4 and 16.0% lower than with below-elbow (BE) stimulation, respectively. With heating the elbow to 42 degrees C, these differences increased significantly to 28.9 and 26.9% (P=0.019 and 0.029), respectively. The mean CV reduction in the across-elbow segment relative to the forearm segment also increased from 20.5 m/s at 32 degrees C to 25.6 m/s at 42 degrees C (P=0.0010). Across-elbow CV at 32 degrees C correlated with increased CB (as measured by amplitude) with heating (r=0.53, P=0.048) and approached significance for area (r=0.48, P=0.068) Likewise, baseline CB at 32 degrees C correlated with the likelihood of increased CB for amplitude (r=0.77, P<0.001), and approached significance for area (r=0.47, P=0.079). CONCLUSIONS: Elbow heating in UNE increases the relative drop in across-elbow CV and the degree of across-elbow CB; absolute across-elbow CV and the presence of baseline CB at 32 degrees C are good predictors of this latter effect.     

The "Gulf War syndrome". Is there evidence of dysfunction in the nervous system?

In a pilot study, 14 Gulf War veterans were randomly selected from a large list of those with unexplained illness, to compare the functional integrity of the peripheral and central nervous system with a group of 13 healthy civilian control subjects using predetermined outcome measures. The controls were matched closely for age, sex, handedness, and physical activity. Outcome measures included scoring of symptoms and clinical neurological signs, quantitative sensory testing of heat, cold and vibration sensibilities, motor and sensory nerve conduction studies on upper and lower limbs, needle EMG of distal and proximal muscles and multimodality evoked potential (visual, brainstem, and somatosensory) studies. Three measurements, all related to peripheral nerve function (cold threshold (P = 0.0002), sural nerve latency (P = 0.034), and median nerve sensory action potential (P = 0.030) were abnormal in the veterans compared with the controls. There may be a dysfunction in the veterans but more studies are required to investigate the findings further and to characterise the dysfunction if confirmed.     

Sensory nerve conduction deficit in experimental monoclonal gammopathy of undetermined significance (MGUS) neuropathy

An emerging body of evidence from in vitro studies and in vivo animal models supports a pathogenic role of antibodies in the development of peripheral neuropathy associated with monoclonal gammopathy of undetermined significance (MGUS). Although the assessment of motor and sensory nerve fiber function is of clinical importance, it is seldom applied experimentally. We describe the application of an electrophysiologic method for the evaluation of motor and sensory nerve fiber function using an experimental model of MGUS neuropathy. Supramaximal stimulation of the tibial nerve elicited an early motor response (M-wave, 1.7 +/- 0.1 ms, n = 10) and a late sensory (H-reflex, 7.8 +/- 0.1 ms, n = 10) response that was recorded from the hind foot of anesthetized rats. Intraneural injection of serum antibodies from a MGUS patient with sensorimotor polyneuropathy, but not from an age-matched control subject, produced a marked attenuation of the H-reflex (P < 0.01, n = 10) without affecting the M-wave. Light and electron microscopy of affected nerve showed myelinoaxonal degeneration with sparing of the smaller unmyelinated nerve fibers. The combined electrophysiologic and morphologic findings presented in this study are consistent with a selective sensory conduction deficit in MGUS neuropathy. Selective injury of afferent nerve fibers by this patient's serum antibodies may result from reactivity to neural antigens uniquely expressed by sensory neurons.     

Mice lacking basic fibroblast growth factor showed faster sensory recovery

Neurotrophic factors have been shown to stimulate and support peripheral nerve repair. One of these factors is basic fibroblast growth factor (FGF-2), which is up-regulated after peripheral nerve injury and influences early sciatic nerve regeneration by regulating Schwann cell proliferation. Our previous study on FGF-2 deficient mice indicated that FGF-2 is important for axonal maturation and remyelination one week after sciatic nerve crush (Jungnickel, J., Claus, P., Gransalke, K., Timmer, M. and Grothe, C., 2004. Targeted disruption of the FGF-2 gene affects the response to peripheral nerve injury. Mol. Cell. Neurosci. 25, 444-452). However, the functional impact of these effects on sensory and motor fibers was not clear. After performing pinch test, walking track analysis and rotarod, we found faster recovery of mechanosensory but not of motor function in mutant mice. To elucidate the role of FGF-2 on structural recovery, we analyzed FGF-2 deficient mice and wild-type littermates 2 and 4 weeks after sciatic nerve crush. Two weeks after peripheral nerve injury, regenerating fibers of mutant mice showed both significantly increased axon and myelin size, but no difference in the number of myelinated and unmyelinated fibers. Molecular analysis indicated that the expression level of myelin protein zero was significantly enhanced in lesioned nerves in the absence of FGF-2. These results suggest that loss of FGF-2 could positively influence restoration of mechanosensory function by accelerating structural recovery transiently.     

Diabetes, peripheral neuropathy, and old age disability.

The purpose of this study was to determine whether peripheral neuropathy explains the apparent association between diabetes and disability in old age, and to evaluate the utility of lower extremity function tests in older diabetic adults with and without neuropathy. We evaluated 39 adults, aged 70-79 years, for pressure sensation (log(10)g), vibration perception threshold (VPT; microns), and electrophysiologic function of the peroneal nerve. The subjects included patients with established diabetic neuropathy (DN; n = 14), diabetic controls without neuropathy (DC; n = 13), and nondiabetic controls (NDC; n = 12). Nonparametric statistical methods were used to relate neuropathy measures to performance in tests of walking speed, static and dynamic balance, coordination, and ankle strength (kilograms). Significant age-adjusted correlations were observed between measures of sensory neuropathy and a variety of performance measures, and electrophysiologic measures were related to static balance. DN subjects had significantly higher pressure sensation than NDC (5.17 vs 3.38g, P < 0.05), higher VPT (62.5 vs 21.7 microm, P < 0.05), and lower peroneal motor response amplitudes at multiple sites. Pressure sensation and nerve conduction measures did not differ between DC and NDC. Compared with NDC, DN subjects performed significantly worse on tests of walking speed (0.99 vs 1.34 m/s; P < 0.05), static balance (4.9 vs 20.4 s; P < 0.05), dynamic balance (9.23 vs 25.52 s; P < 0.05), and coordination (6.73 vs 4.76 s; P < 0.05). No differences were observed in these measures between DC and NDC. Observed differences in physical abilities between older diabetic and nondiabetic adults may have been due to the subset of diabetic individuals with peripheral neuropathy. Quantitative measures of sensory and motor nerve function have distinct effects on physical performance. Interventions aimed at reducing the impact of diabetes-associated disability in old age may have the greatest impact among people with peripheral neuropathy.     

Spinal arteriovenous malformations: Clinical and neurophysiological findings

Eighteen patients with dural arteriovenous fistulas or intradural arteriovenous malformations underwent clinical and neurophysiological examination. Bladder disturbances, pain, sensory abnormalities and involvement of both upper and lower motor neurons were commonly observed. Abnormal findings were obtained both in electromyography (11/18) and somatosensory evoked potentials (16/18). The motor evoked potentials were abnormal in all but one patient and showed a prolonged central (n = 14) or peripheral motor conduction time (n = 6). In three cases both values were prolonged. The results of nerve conduction studies in the patients with prolonged peripheral motor conduction times were normal. These neurophysiological findings may indicate root involvement in some patients, probably due to venous congestion and consequent hypoxia, as there were no signs of root compression on neuroradiological evaluation in any of these six patients. Motor evoked potentials may provide an additional clue to the diagnosis, although patients with spinal stenosis or motor neuron disease may present with similar findings.     

Multifocal neural conduction impairment in forestry workers exposed and not exposed to vibration.

OBJECTIVE: The aim of the study was to assess peripheral neural involvement induced by exposure to hand-arm vibration. METHODS: Twenty lumberjacks, working regularly with chain-saws and exposed to hand-arm vibration (group E) and 20 forestry workers performing heavy manual work and not exposed to vibration (group NE) were matched with a control group of 20 healthy non-manual workers (group C). The subjects of groups E and NE, all symptomatic, and of group C underwent extensive bilateral neurophysiological examination consisting of: sensory conduction (velocity and amplitude) of radial, median and ulnar nerves in digit-wrist segments; sensory conduction (velocity) of median nerve in wrist-elbow segment; mixed conduction (velocity and amplitude) of median and ulnar nerves in palm-wrist segments; motor conduction velocity, including distal motor latencies, and amplitude of median (elbow-wrist) and ulnar (elbow-wrist and across the elbow) nerves. RESULTS: Electrophysiological abnormalities were found in 85% of group E's limbs, versus 62.5% of group NE's limbs. The most frequent pathological pattern in group E was a 'multifocal' impairment (multiple sites of several nerve segments), with a prevalent involvement of sensory rather than motor fibres in the hand, seldom extending to the forearm. Multivariate analysis showed that the neurographic parameters which better characterized workers exposed to hand-arm vibration had a pattern different from that usually found in idiopathic carpal tunnel syndrome (CTS). CONCLUSION: These results suggest that vibration-induced neural involvement can be considered neither pure digital neuropathy, nor definite CTS, as previously described.     

Correlation of vibratory quantitative sensory testing and nerve conduction studies in patients with diabetes

Monitoring the course of diabetic peripheral neuropathy (DPN) remains a challenge. Besides clinical examination, nerve conduction studies (NCS) and quantitative sensory testing (QST) are the most commonly used methods for evaluating peripheral nerve function in clinical trials and population studies. In this study the correlation between vibratory QST and NCS was determined. Patients (N = 227) with diabetes mellitus participated in this multicenter, single-visit, cross-sectional study. QST of vibration measured with the CASE IV system was compared with a composite score of peroneal motor and tibial motor NCS and with individual attributes of peroneal, tibial, and sural nerves. The correlation between QST and composite score of NCS was 0.234 (Pearson correlation coefficient, P = 0.001). The correlations between QST and individual attributes of NCS ranged from 0.189 to 0.480 (Pearson correlation coefficients, P < 0.001). The low to moderate correlation between QST and NCS suggests that these tests cannot replace each other but are complementary.     

Strength-duration properties of peripheral nerve in acquired neuromyotonia.

The strength-duration time constant (SDTC) of a myelinated axon is a property of the nodal membrane and is sensitive to changes in membrane potential. Strength-duration time constants for motor axons and cutaneous afferents of the median nerve were measured in 9 patients with acquired neuromyotonia (NMT), a condition of peripheral nerve hyperexcitability, and 15 control patients. Mean motor axon time constants were significantly prolonged (344 +/- 100 micros) in patients compared to healthy controls (264 +/- 34 micros; P = 0.038), but sensory axon time constants were not significantly different. Motor axon time constants were longer than sensory axon time constants in 4 of the patients with neuromyotonia, suggesting that the nodal membrane was depolarized by an ectopic focus at the site of nerve stimulation at the wrist, ionic conductances were altered at the node, or that the size of the node was increased, possibly as a result of immune-mediated damage. The anti-voltage-gated potassium channel antibodies thought to generate peripheral nerve hyperexcitability in acquired neuromyotonia may be indirectly responsible for changes in motor axon nodal membrane properties.     

Measuring conduction velocity distributions in peripheral nerves using neurophysiological techniques

ObjectiveTo determine how long it takes for neural impulses to travel along peripheral nerve fibers in living humans.MethodsA collision test was performed to measure the conduction velocity distribution of the ulnar nerve. Two stimuli at the distal and proximal sites were used to produce the collision. Compound muscle or nerve action potentials were recorded to perform the measurements on the motor or mixed nerve, respectively. Interstimulus interval was set at 1–5 ms. A quadri-pulse technique was used to measure the refractory period and calibrate the conduction time.ResultsCompound muscle action potential produced by the proximal stimulation started to emerge at the interstimulus interval of about 1.5 ms and increased with the increment in interstimulus interval. Two groups of motor nerve fibers with different conduction velocities were identified. The mixed nerve showed a wider conduction velocity distribution with identification of more subgroups of nerve fibers than the motor nerve.ConclusionsThe conduction velocity distributions in high resolution on a peripheral motor and mixed nerve are different and this can be measured with the collision test.SignificanceWe provided ground truth data to verify the neuroimaging pipelines for the measurements of latency connectome in the peripheral nervous system.     

Neurotrophin-3 reverses nerve conduction velocity deficits in streptozotocin-diabetic rats

The ability of neurotrophin-3 (NT-3) to reverse established nerve disorders was investigated in the peripheral neuraxis of streptozotocin-diabetic rats. Sciatic sensory and motor nerve conduction velocity deficits established after 2 months of diabetes were completely normalized by one further month of treatment with either NT-3 or insulin. None of these conduction velocity changes were associated with altered mean axonal caliber in the sciatic nerve. In the dorsal and ventral roots, mean axonal caliber was significantly decreased after 8 weeks of diabetes (both P < 0.05). Subsequently, one month of insulin, but not NT-3, treatment increased mean axonal caliber to age-matched control values. NT-3 treatment was also without effect on the significant (both P < 0.05) decrease in phosphorylated heavy neurofilament (NFH) subunits seen in dorsal and ventral roots of 12 week diabetic rats. In the sural nerve, diabetes attenuated a maturation-associated increase in mean axonal caliber over the first 8 weeks of diabetes, and induced atrophy between weeks 8 and 12 that was ameliorated by both NT-3 and insulin treatment. Reductions in sural nerve axonal caliber were associated with a tendency for elevation of both phosphorylated NFH levels in large fibers and the ratio of phosphorylated to nonphosphorylated NFH that was attenuated by NT-3. These data demonstrate that NT-3 corrects established sciatic nerve conduction deficits in diabetic rats in a manner independent of changes in axonal caliber in this nerve. Further, although NT-3 was without effect on decreases in axonal caliber and NFH subunit phosphorylation in the spinal roots, reversal of axonal caliber deficits in peripheral nerves of sensory fibers may involve NT-3-mediated normalization of aberrant neurofilament phosphorylation.     

The influence of temperature on conduction block

In nerve conduction studies, it may be difficult to distinguish conduction block from increased temporal dispersion. We assessed whether a better distinction is possible by warming, because this increases the number of blocked nerve fibers and decreases temporal dispersion. We investigated 11 patients with conduction block in the median or ulnar nerve. Motor conduction was studied at 25 degrees C and at 40 degrees C. The amplitude reduction and area reduction were significantly greater at 40 degrees C than at 25 degrees C. Significantly more nerve segments fulfilled criteria for conduction block at 40 degrees C than at 25 degrees C. The duration prolongation was slightly smaller at 40 degrees C. These results indicate that, in demyelinating neuropathies, an increase in temperature increases the number of blocked nerve fibers and decreases temporal dispersion. Conduction block may therefore be missed when the investigated limb is too cold. Based on our study, we also propose a criterion for conduction block that is based on the influence of temperature.     

SENSORY-MOTOR POLYNEUROPATHY IN A PATIENT WITH MITOCHONDRIAL MYOPATHY

Aim of the study : To evaluate with neurophysiological methods whether gene therapy may improve the abnormalities of motor system in mice with Metachromatic Leukodystrophy (MLD). Methods : 2 groups were studied: the first one consisted of 11 mice (AS2-/-) knocked-out for Arylsulfatase A (ARSA) gene; the second one included 10 mice (AS2-/-tr) which, after lethal irradiation, were transplanted with autologous hematopoietic stem cells transducted with a retroviral vector containing the ARSA cDNA. Both groups underwent Motor Evoked Potentials (MEP) by transcranial electrical stimulation of motor cortex, as well as Motor Conduction Velocity (MCV) of ischiatic nerve and compared with a control group (n=11). Results : The mean latency of cortical MEP was shorter in AS2-/-tr than in AS2-/- group of mice (4.9 ± 0.2 versus 6.8 ± 1.2 msec; p<0.001), being quite similar to controls (5.1 ± 0.4 msec). The mean MCV was higher in AS2-/-tr as compared to AS2-/- group (27.1 ± 4.5 versus 22.8 ± 3.0 m/sec; p<0.05), even though significantly slower than controls (37.7 ± 3.8 m/sec). Comments : The neurophysiological data show that gene therapy seems to prevent ARSA deficient mice from developing a functional damage of corticospinal pathways. They also suggest that peripheral neuropathy has a slower course in mice treated with gene therapy, although motor nerve fibers are not completely spared.     

Selective reinnervation of distal motor stumps by peripheral motor axons

Random matching of regenerating axons with Schwann tubes in the distal nerve stump is thought to contribute to the often poor results of peripheral nerve repair. Motor axons would be led to sensory end organs and sensory axons to motor end plates; both would remain functionless. However, the ability of regenerating axons to differentiate between sensory and motor environments has not been adequately examined. The experiments reported here evaluated the behavior of regenerating motor axons when given equal access to distal sensory and motor nerve stumps across an unstructured gap. "Y"-shape silicon chambers were implanted within the rat femoral nerve with the proximal motor branch as axon source in the base of the Y. The distal sensory and motor branches served as targets in the branches of the Y, and were placed 2 or 5 mm from the axon source. After 2 months for axon regeneration, horseradish peroxidase was used to label the motoneurons projecting axons into either the motor or the sensory stump. Equal numbers of motoneurons were labeled from the sensory and motor stumps at 2 mm, but significantly more motoneurons were labeled from the motor stump at 5 mm. (P = 0.016). This finding is consistent with selective reinnervation of the motor stump. Augmentation of this phenomenon to produce specific reunion of individual motor axons could dramatically improve the results of nerve suture.     

Peripheral nerve endoneurial microangiopathy and necrosis in rats with insulinoma

Peripheral nerve pathology related to chronic hyperinsulinemia and hypoglycemia has yet to be fully explored. Here we conducted a systematic quantitative analysis of morphological alterations in peripheral sensory and motor nerve fibers and endoneurial microvasculature in longstanding insulinoma-carrying rats (I-rats; n=12). Age-matched normal rats (n=6) served as controls. Over the 15-month observation period, two of I-rats developed paresis of the hind limbs when their blood glucose level fell below 1.7 mmol/l. These animals showed a massive myelinated fiber loss associated with active degeneration of residual myelinated fibers and multiple endoneurial microvascular occlusions at the sciatic nerve level. The rest of the non-paretic I-rats showed a decreased density of large myelinated fibers with axonal degeneration in the peroneal nerve and an increased density of small myelinated fibers with preserved morphology in the sural nerve. This was associated with endoneurial microangiopathic changes indicative of endoneurial ischemia/hypoxia in the sciatic and peroneal nerves, and an increase in endoneurial microvascular density in the sciatic and sural nerves. In conjunction with previous data, these findings suggest that the observed increase in endoneurial microvascular density may be a compensatory response to endoneurial ischemia/hypoxia induced by chronic hyperinsulinemia in I-rats without paresis. In conclusion, the present study showed characteristic morphological alterations in peripheral sensory and motor nerve fibers associated with microangiopathy indicative of endoneurial ischemia/hypoxia in the sciatic and peroneal nerves, and provides the first evidence for the occurrence of endoneurial necrosis in the sciatic nerve, to which the hind limb paresis can be ascribed in I-rats.     

Stress exposure modulates peptidergic innervation and degranulates mast cells in murine skin

Stress is said to induce itchiness of the skin, exacerbate inflammatory skin diseases, and inhibit wound healing. Neuropeptides such as substance P (SP) may play a role in these processes. Recently, we were able to show that both stress or SP are associated with neurogenic inflammation and increased apoptosis in the murine hair follicle. Moreover, peptidergic cutaneous innervation is subject to lifelong plasticity due to its association with the cyclic growth of hair follicles. However, peripheral neuronal plasticity has never been reported in altered interactions between the nervous and immune systems under perceived stress. Here, we show for the first time plasticity of the cutaneous peptidergic innervation in response to stress. After exposure to sonic stress, the number of SP+ nerve fibers in the back skin of C57BL/6 mice with their hair follicles in the resting phase of the hair cycle (telogen-low numbers of nerve fibers) increased significantly. Such nerve fibers contacted mast cells more frequently. At the same time, the percentage of degranulated mast cells increased significantly associated with a rise in apoptotic cells in the skin. Increased numbers of peptidergic nerve fibers correlated with increased numbers of growth-associated protein 43 (Gap-43)+ nerve fibers, which is a marker for growing nerves. Thus, neuronal plasticity and increased neuro-immune interaction occur under stress and may alter inflammatory skin diseases and trophic functions in the skin where neurogenic inflammation plays a part.     

Evaluation of dermal myelinated nerve fibers in diabetes mellitus

Skin biopsies have primarily been used to study the non‐myelinated nerve fibers of the epidermis in a variety of neuropathies. In this study, we have expanded the skin biopsy technique to glabrous, non‐hairy skin to evaluate myelinated nerve fibers in the most highly prevalent peripheral nerve disease, diabetic polyneuropathy (DPN). Twenty patients with DPN (Type I, n = 9; Type II, n = 11) and 16 age‐matched healthy controls (age 29–73) underwent skin biopsy of the index finger, nerve conduction studies (NCS), and composite neuropathy scoring. In patients with DPN, we found a statistically significant reduction of both mechanoreceptive Meissner corpuscles (MCs) and their afferent myelinated nerve fibers (p = 0.01). This myelinated nerve fiber loss was correlated with the decreased amplitudes of sensory/motor responses in NCS. This study supports the utilization of skin biopsy to quantitatively evaluate axonal loss of myelinated nerve fibers in patients with DPN.     

Topographical distribution of motor fascicles in the sciatic‐tibial nerve of the rat

Knowledge of the intraneural topography of peripheral nerves may help to improve nerve repair after injuries and the selectivity of neural interfaces. We studied the fascicular pattern of motor fibers of the rat sciatic–tibial nerve. We carried out an anatomical dissection of the muscular tributaries of the tibial nerve in the leg. Immunohistochemistry against choline acetyltransferase was used to identify motor axons. Retrograde tracing allowed localization of the muscular fascicles at proximal levels of the sciatic trunk. The distribution of motor fibers in transverse section of the tibial nerve is not homogeneous; two clusters were identified, each one containing fibers of functionally related muscles. Retrograde tracing allowed for the identification of motor fascicles, each one well localized along the sciatic nerve. In the rat there is a somatotopic organization of the sciatic nerve, with muscular fascicles maintaining the same relative position along the entire nerve. Muscle Nerve, 2010     

Charcot-Marie-Tooth disease: a novel Tyr145Ser mutation in the myelin protein zero (MPZ,P0) gene causes different phenotypes in homozygous and heterozygous carriers within one family

Charcot-Marie-Tooth disease type 1B (CMT 1B) is caused by mutations in the gene coding for peripheral myelin protein zero (MPZ, P0) that plays a fundamental role in adhesion and compaction of peripheral myelin. Here we report a Costa Rican family with a hereditary peripheral neuropathy due to a novel Tyr145Ser MPZ mutation. Four family members were heterozygously affected; two siblings of two heterozygous carriers were homozygous for this mutation. On neurological examination the heterozygous parents and their homozygous children both showed distal sensory deficits. The mother and the siblings displayed impaired deep tendon reflexes and mild sensory ataxia. The homozygous individuals were more severely affected with an earlier age of onset, distal motor weakness, and pupillary abnormalities. Electrophysiological studies revealed both signs of demyelination and axonal nerve degeneration. The sural nerve biopsy of one sibling showed thinly myelinated nerve fibers, onion bulb formation, and clusters of regenerating fibers. On electron microscopy axonal degeneration and decompaction of inner myelin layers were found. This Costa Rican family shows phenotypic variability depending on the homozygous or heterozygous state of the Tyr145Ser mutation carriers.A. Leal and C. Berghoff contributed equally to this work.     

Activation and sensitization of C and Adelta afferent fibers mediated by P2X receptors in rat dorsal skin

The present study investigated the activation and sensitization effects of local injection of P2X receptor agonist alpha,beta-methylene ATP (alphabeta-meATP) into the receptive fields of afferent fibers innervating dorsal hairy skin in anesthetized rats. Single unit activities of afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branch. A total of 237 fibers were obtained. Of these, 67 were classed as C fibers, 104 as Adelta fibers and 66 as Abeta fibers. When alphabeta-meATP (0.1-100 microM, 10 microl) was injected subcutaneously into the receptive fields of these units, C and Adelta fibers demonstrated a dose-related increase in the discharge rates of the response. The activated proportion of C and Adelta fibers with a response to the drug also increased with dose. However, Abeta fibers did not exhibit significant activation. Furthermore, injection of alphabeta-meATP (10 microl) at a concentration of 100 microM resulted in a significant decrease of mechanical thresholds in C and Adelta fibers compared with pre-injection baseline (P < 0.05). In control experiments, injection of the vehicle phosphate-buffered saline (PBS, 10 microl) had no effect on all units tested. alphabeta-meATP (100 microM, 10 microl) followed by pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), a P2X receptor antagonist, successfully blocked the activation and sensitization effects of alphabeta-meATP on C and Adelta fibers tested. These results suggest that peripheral P2X receptors are involved in mediating peripheral excitation of C and Adelta fibers.