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H R Weng

Publications and source records attributed to H R Weng.

14 recordsLinked to original sources
PubMed2006

Clinical and experimental findings in humans and animals with chemotherapy-induced peripheral neuropathy.

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.

Animals↗
PubMed2001

Sensory processing in the deep spinal dorsal horn of neurokinin-1 receptor knockout mice.

BACKGROUND: The neurokinin-1 receptor and its primary ligand, substance P, are widely recognized as contributing to the spinal processing of nociceptive stimuli, yet the specific function of the neurokinin-1 receptor remains unclear. METHODS: To better clarify these functions, the authors examined the neurophysiologic responses of L4-L5 neurons in the deep dorsal horn to acute mechanical, thermal, and electrical stimuli in knockout and wild-type mice. In addition, the capacity of knockout and wild-type mice to show wind-up to repeated C-fiber stimuli and to show sensitization after cutaneous mustard oil was assessed. RESULTS: A total of 68 nociceptive neurons (35 in knockout, 33 in wild type) in laminae III-V were studied. No differences in the acute responses of neurons in knockout and wild-type mice to graded mechanical, thermal, or electrical stimuli or in the acute responses to mustard oil were observed. However, wind-up to repeated electrical stimulation at C-fiber intensity was significantly attenuated in the knockout mice compared with wild type controls. In addition, mustard oil-induced mechanical hypersensitivity was significantly reduced in the knockout mice. CONCLUSIONS: These results indicate that neurokinin-1 receptors do not play a significant role in the responses of nociceptive neurons in the deep spinal dorsal horn to acute noxious mechanical, thermal, electrical, or chemical stimuli. On the other hand, neurokinin-1 receptors are critical for the central hyperexcitability that is observed in these neurons with repeated C-fiber inputs and to the central sensitization induced by topical mustard oil application.

Animals↗
PubMed2000

Functional plasticity in primate somatosensory thalamus following chronic lesion of the ventral lateral spinal cord.

The long-term consequences of thoracic spinothalamic tract lesion on the physiological properties of neurons in the ventral posterior lateral nucleus of the thalamus in monkeys were assessed. Neurons responding to both compressive and phasic brush stimuli (multireceptive neurons), but not brush-specific (low-threshold) neurons, in the partially deafferented thalamus showed increased spontaneous activity, increased responses evoked by cutaneous stimuli and larger mean receptive field size than the same types of cells in the thalamus with intact innervation. The spike train properties of both the spontaneous and evoked discharges of cells were also altered so that there was an increased incidence of spike-bursts in cells of deafferented thalamus. These changes were widespread in the thalamus, and included cells in both the fully innervated forelimb representation and the partially denervated hindlimb representation ipsilateral to the lesion. The spontaneous and evoked spike trains in the ipsilateral thalamus also show increased frequency of both spike-burst and non-burst events compared to the intact thalamus. These results indicate that chronic spinothalamic tract lesion produces widespread changes in the physiological properties of a discrete cell population of the thalamus.The findings in this study indicate that the thalamic processing of somatosensory information conveyed by the lemniscal system is altered by transection of the spinothalamic tract. This change in sensory processing in the thalamus would result in altered cortical processing of innocuous somatosensory inputs following deafferentation and so possibly contribute to the generation of the central pain syndrome.

Action Potentials↗
PubMed1998

GABAA receptor blockade inhibits A beta fibre evoked wind-up in the arthritic rat.

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.

Animals↗
PubMed1998

On the cutaneous receptors contributing to withdrawal reflex pathways in the decerebrate spinal rat.

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.

Animals↗
PubMed1997

Developmental adaptation of rat nociceptive withdrawal reflexes after neonatal tendon transfer.

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.

Adaptation, Physiological↗
PubMed1996

Nociceptive inhibition of withdrawal reflex responses increases over time in spinalized rats.

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.

Animals↗
PubMed1996

Cutaneous inhibitory receptive fields of withdrawal reflexes in the decerebrate spinal rat.

1. The inhibitory cutaneous input to the withdrawal reflex pathways to single hindlimb muscles was investigated in decerebrate spinal rats (n = 53) using electromyography. 2. Withdrawal reflexes in the peronei, extensor digitorum longus and tibialis anterior muscles of the leg were strongly inhibited by conditioning mechanical, thermal (CO2 laser) and intracutaneous electrical stimulation of specific skin areas. By contrast, withdrawal reflexes in the biceps posterior-semitendinosus muscles of the thigh could only be weakly inhibited by conditioning skin stimulation. 3. Powerful inhibition of withdrawal reflexes in single lower leg muscles was elicited from the ipsilateral hindpaw plantar area, which would move towards the stimulation on contraction in the respective muscle. In addition, weak nociceptive inhibition was evoked from the corresponding skin areas on the contralateral hindlimb and, in some muscles, the tail. 4. The ipsilateral inhibitory and excitatory receptive fields of the withdrawal reflexes in single muscles overlapped somewhat. On stimulation of these transitional areas the reflex responses were preceded by a short-lasting inhibition. 5. Graded mechanical and thermal stimulation demonstrated prominent inhibitors effects from nociceptive receptors. Weak inhibitory effects were elicited by innocuous mechanical stimulation, suggesting a weak contribution from low threshold mechanoreceptors. Latency measurements indicated an inhibitory input from both myelinated and unmyelinated fibres. 6. In conclusion, the withdrawal reflex pathways receive a powerful nociceptive inhibitory input through spinal pathways. The movement-related organization of this input suggests that it serves to prevent inappropriate withdrawal reflexes.

Animals↗
PubMed1995

A survey of spinal dorsal horn neurones encoding the spatial organization of withdrawal reflexes in the rat.

The withdrawal reflex pathways to hindlimb muscles have an elaborate spatial organization in the rat. In short, the distribution of sensitivity within the cutaneous receptive field of a single muscle has a spatial pattern that is a mirror image of the spatial pattern of the withdrawal of the skin surface ensuing on contraction in the respective muscle. In the present study, a search for neurones encoding the specific spatial input-output relationship of withdrawal reflexes to single muscles was made in the lumbosacral spinal cord in halothane/nitrous oxide-anaesthetized rats. The cutaneous receptive fields of 147 dorsal horn neurones in the L4-5 segments receiving a nociceptive input and a convergent input from A and C fibres from the hindpaw were studied. The spatial pattern of the response amplitude within the receptive fields of 118 neurones was quantitatively compared with those of withdrawal reflexes to single muscles. Response patterns exhibiting a high similarity to those of withdrawal reflexes to single muscles were found in 27 neurones located in the deep dorsal horn. Twenty-six of these belonged to class 2 (responding to tactile and nociceptive input) and one belonged to class 3 (responding only to nociceptive input). None of the neurones tested (n = 20) with reflex-like response patterns could be antidromically driven from the upper cervical cord, suggesting that they were spinal interneurones. With some overlap, putative interneurones of the withdrawal reflexes to the plantar flexors of the digits, the plantar flexors of the ankle, the pronators, the dorsiflexors of the ankle, and a flexor of the knee, were found in succession in a mediolateral direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Sensorimotor transformation in a spinal motor system.

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.

Animals↗
PubMed1993

Nociceptive C fibre input to the primary somatosensory cortex (SI). A field potential study in the rat.

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.

Animals↗
PubMed1993

Multiple spinal pathways mediate cutaneous nociceptive C fibre input to the primary somatosensory cortex (SI) in the rat.

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.

Animals↗
PubMed1992

Functional organization of the nociceptive withdrawal reflexes. II. Changes of excitability and receptive fields after spinalization in the rat.

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.

Animals↗