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Esophageal squamous cell carcinoma (ESCC) in the young patients is comparatively rare and has not been well studied. We analyzed the clinical and survival data of 127 ESCC patients <40 years at a single high-volume center and compared with those of 4109 ESCC patients ≥40 years who underwent surgery within the same period in this study. The average age was 36.5 ± 0.2 years for the young patient group, with the youngest aged 26 years. Young patients had a higher rate of family history, longer tumors, and a more advanced pT category than their older counterparts. Moreover, more patients in the young group underwent incomplete resection (19.7% vs. 8.9%, P  < 0.001) and adjuvant therapy (40.9% vs. 30.8%, P  = 0.015). The overall survival (OS) and cancer-specific survival (CSS) between patients <40 years and patients ≥40 years were not significant in the entire group. In the subgroup analysis, the OS and CSS rates for patients <40 years were significantly worse than patients ≥40 years in subgroups of pTNM stage III and incomplete resections. In conclusions, young patients with ESCC were more likely to have family history and present with advanced disease. The survival for young patients with ESCC was poorer than their older counterparts in patients with later stage diseases. [ABSTRACT FROM AUTHOR]

Activation of glutamate receptors and glial cells in the spinal dorsal horn are two fundamental processes involved in the pathogenesis of various pain conditions, including neuropathic pain induced by injury to the peripheral or central nervous systems. Numerous studies have demonstrated that minocycline treatment attenuates allodynic and hyperalgesic behaviors induced by tissue inflammation or nerve injury. However, the synaptic mechanisms by which minocycline prevents hyperalgesia are not fully understood. We recently reported that deficient glutamate uptake by glial glutamate transporters (GTs) is key for the enhanced activation of N-methyl-d-aspartate (NMDA) receptors in the spinal sensory synapses of rats receiving partial sciatic nerve ligation (pSNL). In this study, we investigated how minocycline affects activation of NMDA receptors in the spinal sensory synapses in rats with pSNL by whole cell recordings of NMDA currents in spinal laminea I and II neurons from spinal slices. The effects of minocycline treatments on the dorsal horn expression of glial GTs and astrocyte marker glial fibrillary acidic protein (GFAP) were analyzed by immunohistochemistry. We demonstrated that normalized activation of NMDA receptors in synapses activated by both weak and strong peripheral input in the spinal dorsal horn is temporally associated with attenuated mechanical allodynia in rats with pSNL receiving intraperitoneal injection of minocycline. Minocycline ameliorated both the downregulation of glial GT expression and the activation of astrocytes induced by pSNL in the spinal dorsal horn. We further revealed that preventing deficient glial glutamate uptake at the synapse is crucial for preserving the normalized activation of NMDA receptors in the spinal sensory synapses in pSNL rats treated with minocycline. Our studies suggest that glial GTs may be a potential target for the development of analgesics., (Copyright © 2010 IBRO. Published by Elsevier Ltd. All rights reserved.)

Pain arises from numerous causes in cancer patients. Well known to cancer care providers, but perhaps less well so to others, is that the main causes of pain in cancer patients in fact arise due to cancer treatments more so than the disease itself. In this paper clinical and laboratory findings on the characteristics of chemotherapy-induced neuropathic pain are reviewed and a scheme for the underlying mechanisms is outlined.

To clarify the mechanisms of allodynia we have examined whether 'wind-up' of nociceptive withdrawal reflexes (NWR), a phenomenon characteristic of nociceptive C fiber spinal processing, can be mimicked by stimulation of tactile A beta fibers in monoarthritic decerebrate spinal rats. Knee joint monoarthritis was induced by carrageenan/kaolin under halothane anaesthesia 5 h before recordings. In arthritic, but not in control rats, wind-up of NWR of the semitendinosus muscle could be evoked by repeated stimulation of A beta fibres. By contrast, peroneus longus reflexes did not exhibit marked wind-up. Bicuculline (0.03-0.3 mg/kg, i.v.) dose-dependently inhibited this wind-up. Hence, reflex wind-up can be elicited by tactile A beta fibers in arthritis rats through a GABAA dependent mechanism.

Previous studies indicate that the withdrawal reflex system in the rat has a "modular" organization, each reflex pathway performing a specific sensorimotor transformation. Here, we wished to clarify which cutaneous receptors contribute to this system and to determine whether there are differences in this respect between reflex pathways of different muscles. Withdrawal reflexes of the peroneus longus, extensor digitorum longus, and semitendinosus muscles were recorded with EMG techniques during high reflex excitability in decerebrate spinal rats (n=26). While maintained innocuous pressure on glabrous skin could elicit a sustained reflex activity in all muscles studied, vibration of glabrous skin (10-300 Hz) always failed to evoke a reflex response, suggesting that slowly adapting, but not rapidly adapting, low-threshold mechanoreceptive fibers from this type of skin contribute to withdrawal reflex pathways. Thermal stimulation in the innocuous range, i.e., cooling from 32 to 17 degrees C, or warming the skin from 32 to 41 degrees C, always failed to produce reflex responses, indicating that neither cold nor warm receptors contribute to withdrawal reflex pathways. When either cooling or warming the skin to the noxious temperatures of 1 degrees C or above 45 degrees C, respectively, a reflex discharge was often evoked in the muscles studied. Intradermal administration of histamine, a potent pruritogenic substance, produced very weak, or no, reflex response. In contrast, mustard oil produced vigorous reflex responses in all muscles studied. These findings suggest that some chemonociceptors contribute only weakly, or not at all, to withdrawal reflex pathways. The present data suggest that a selective set of cutaneous receptors contribute to withdrawal reflex pathways and that different withdrawal reflex pathways receive input from essentially the same cutaneous receptor types.

Nociceptive withdrawal reflexes (NWRs) were studied in adult rats in which the movement patterns produced by single muscles had been altered by neonatal tendon transfer. NWRs evoked by cutaneous noxious mechanical and thermal (CO2-laser) stimulation were recorded using electromyography in a decerebrate spinal preparation. The sensitivity distribution within the receptive fields of the NWRs of the extensor digitorum longus and the peronei muscles exhibited changes corresponding to the altered movement patterns. No detectable change of NWRs was found in normal muscles whose receptive fields overlapped that of the modified muscle. Furthermore, NWRs of muscles that regained an essentially normal function after neonatal tendon transfer did not differ from normal. It is proposed that a developmental experience-dependent mechanism, which takes into account the hindlimb movement pattern caused by contraction of single muscles, underlies the functionally adapted organization of adult NWRs.

Time-dependent changes of nociceptive inhibition of hindlimb withdrawal reflex (WR) pathways were investigated in acute decerebrate spinal rats. Electromyographic recordings of WR of peroneus longus and extensor digitorum longus muscles were made. For each muscle, both short and long latency WR evoked by subcutaneous electrical stimulation and WR evoked by noxious pinch could be inhibited by noxious CO2 laser stimulation of a specific skin area of the ipsilateral hindlimb. The inhibitory effects and size of the inhibitory receptive fields increased spontaneously between two- and three-fold during the first 12 h after spinalization. The functional and possible clinical significance of the strengthened nociceptive inhibitory control and mechanisms underlying the changes of this control after spinal transection are discussed.

To use sensory information from the skin to guide motor behaviour the central nervous system must transform sensory coordinates into movement coordinates. As yet, the basic principles of this crucial neural computation are unclear. One motor system suitable as a model for the study of such transformations is the spinal withdrawal reflex system. The spatial organization of the cutaneous input to these reflexes has been characterized, and we now introduce a novel method of motion analysis permitting a quantitative analysis of the spatial input-output relationship in this motor system. For each muscle studied, a "mirror-image" relationship was found between the spatial distribution of reflex gain for cutaneous input and the pattern of cutaneous unloading ensuing on contraction. Thus, there is an "imprint" of the movement pattern on this motor system permitting effective sensorimotor transformation. This imprint may indicate the presence of a learning process which utilizes the sensory feedback ensuing on muscle contraction.

In the present study, partial lesions of the lower thoracic spinal cord in rats anaesthetized with halothane and nitrous oxide were made in order to elucidate which of the spinal funiculi mediate a nociceptive C fibre input to SI. Field potentials evoked by noxious CO2-laser stimulation were recorded in the left SI. Nociceptive C fibre input from the right hindpaw to SI was propagated by the dorsal funiculi (DF) and the left and right lateral funiculi (LLF and RLF, respectively). Nociceptive C fibre input from the left hindpaw was propagated by LLF and RLF, but not DF. Input from the hindpaws mediated by LLF and RLF caused widespread surface positive potentials throughout most of SI, although potentials in the hindlimb area tended to be larger than those in other areas of SI. Input from the right hindpaw mediated by DF caused surface positive potentials mainly in the hindlimb area of SI. Intracortically, the field potentials reversed polarity in the superficial laminae and had maximal negative amplitudes in laminae III-IV (input transferred by DF and LLF) and in laminae V-VI (input transferred by LLF and RLF). It is concluded that there are multiple spinal pathways which can transfer information from cutaneous nociceptive C fibres to SI in the rat. These ascending pathways seem to activate partly different thalamo-cortical systems.

In the present study, noxious thermal stimulation of the skin with short pulses of CO2-laser radiation was used to identify a cutaneous nociceptive C fibre input to SI and investigate the organization of this input in halothane-nitrous oxide anaesthetized rats. Noxious CO2-laser stimulation of the glabrous skin of the hindpaw consistently evoked late surface positive field potentials in SI (average onset latency 226 ms, peak latency 296 ms). It was demonstrated that these late potentials were evoked by an input from nociceptive C fibres, using a combination of latency measurements, anodal block of A fibre conduction and graded intensities of stimulation. Compared to the tactile evoked potentials in SI, the nociceptive C fibre evoked potentials were more widespread and exhibited a crude somatotopical organization. Intracortically, both tactile and nociceptive C fibre evoked potentials reversed polarity and exhibited a peak negativity in laminae III-IV. The nociceptive C fibre evoked potentials exhibited an additional peak negativity in laminae V-VI. The latter potential had a different time course as compared to the nociceptive C fibre potential evoked in laminae III-IV. In conclusion, an input from cutaneous nociceptive C fibres to SI was demonstrated for the first time in animal experiments. The input to SI from tactile receptors and cutaneous C nociceptors were differently organized.

The spatial organization of the cutaneous input to hindlimb withdrawal reflexes was studied in spinalized, decerebrated, unanesthetized rats. Reflex activity in plantar flexors of the digits, pronators of the foot, dorsiflexors of the digits, and/or the ankle and flexors of the knee was recorded with electromyographic techniques for up to 12 h after spinalization. Graded mechanical (pinch) and thermal stimulation (CO2 laser) of the skin were used. Reflexes were absent ("spinal shock") during approximately 10-20 min after spinalization. The reflex thresholds for pinch and CO2 laser stimulation then decreased considerably during the following 5-8 h. After this time, even mild pressure (less than 0.1 N/mm2) on the skin was sufficient to evoke a reflex in most muscles. During the period from about 0.5-3 h after spinalization, the nociceptive receptive field of each muscle usually corresponded to the area of the skin withdrawn by the muscle. Maximal responses were evoked from the area of the receptive field maximally withdrawn. During this period, responses to innocuous pinch were evoked mainly from the most sensitive area of the receptive fields. Concomitant with the decrease in reflex thresholds, the nociceptive receptive fields expanded for all muscles, often to include areas of the skin not withdrawn by the muscles. For most muscles, reflexes on tactile stimuli were eventually elicited from the entire receptive fields. The receptive fields for thermonociceptive and mechanonociceptive inputs were similar in most muscles. The interossei muscles were exceptional in that they responded very weakly to thermal stimulation. It is concluded that there are neuronal networks in the spinal cord that translate cutaneous nociceptive and tactile input into a withdrawal. However, the control exerted by descending pathways is necessary to maintain a functionally adequate excitability in these reflex pathways and an appropriate size for their receptive fields.