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The involvement of the basal ganglia in motor functions has been well studied. Recent neurophysiological, clinical and behavioral experiments indicate that the basal ganglia also process non-noxious and noxious somatosensory information. However, the functional significance of somatosensory information processing within the basal ganglia is not well understood. This review explores the role of...
We have previously reported that electrical stimulation of cardiac vagal afferents produces an inhibition of the feline's digastric reflex evoked by tooth-pulp stimulation. In the present study, we evaluated whether cardiac vagal afferent stimulation (CVAS) alters the responses of trigeminal sensory neurons to noxious orofacial stimulation in α-chloralose-anesthetized cats. A total of 37 trigeminal...
Mexiletine is widely used for the treatment of neuropathic pain although its site(s) of action remain unclear. Here we have studied the effect of spinal administration of mexiletine (10-1000 μg) on the spontaneous and peripherally evoked responses of spinal neurones of nerve injured (selective ligation of spinal nerves L5-L6; SNL) rats. Sham controls for the surgical intervention were performed. A...
Central sensitization refers to enhanced excitability of dorsal horn neurons and is characterized by increased spontaneous activity, enlarged receptive field (RF) areas, and an increase in responses evoked by large and small caliber primary afferent fibers. Sensitization of dorsal horn neurons often occurs following tissue injury and inflammation and is believed to contribute to hyperalgesia. Windup...
The treatment of pain arising from nerve injury can be difficult and the opioid sensitivity of neuropathic pain remains debatable. Clinical and animal studies report a wide range in the effectiveness of morphine, ranging from inadequate to potent analgesia. In this electrophysiological study we compare the effectiveness of spinal versus systemic administration of morphine on the natural and electrically...
Tumor necrosis factor α (TNF) is a potent pro-inflammatory cytokine that produces pain and hyperalgesia following injection. Its algesic effects are due to sensitizing actions on nociceptive primary afferents and to the upregulation of other pro-inflammatory and algesic proteins. In anesthetized rats, we investigated the effect of subcutaneously injected TNF on background activity and mechanical sensitivity...
A total of 68 neurons were recorded from the ventro-postero-lateral nucleus of thalamus (VPL) in rats with a unilateral chronic constriction injury (CCI) of the sciatic nerve (n=20), sham operation (n=24) and naive rats (n=24), and effects of the lesion of dorsal column (DC) pathway [DC lesion or DC+gracile nucleus lesions] on VPL nucleus neuronal activities were studied. In the VPL nucleus contralateral...
Hyperexcitability of the primary afferent neuron leads to neuropathic pain following injury to peripheral axons. Changes in calcium channel function of sensory neurons following injury have not been directly examined at the channel level, even though calcium is a primary second messenger-regulating neuronal function. We compared calcium currents (I Ca ) in 101 acutely isolated dorsal...
Selective ligation of the L5/L6 spinal nerves produces a partial denervation of the hindpaw and has proved to be a useful model for studying the mechanisms underlying neuropathic pain. Two weeks after surgery, in vivo electrophysiological studies were performed in sham operated and nerve injured rats and the responses of spinal dorsal horn neurones to controlled electrical and natural (mechanical...
The nociceptive flexion reflex (NFR) is a physiological, polysynaptic reflex allowing for painful stimuli to activate an appropriate withdrawal response. NFR is easily measurable in clinical setting, and is a reliable and objective tool for measurement of an individual's pain experience. An exhaustive review of the literature, covering multiple search engines, indicates that the NFR method is valuable...
Galanin is a 29-amino-acid neuropeptide that has been implicated in the processes of nociception. This study examines the effect of exogenous galanin on dorsal horn neurone activity in vivo in the spinal nerve ligation (SNL) model of neuropathic pain. SNL rats but not naive or sham-operated rats exhibited behaviour indicative of allodynia. In anaesthetized rats, extracellular recordings were made...
In superficial layers of the lumbar spinal dorsal horn, N-methyl-d-aspartate-dependent long-term potentiation (LTP) of C fibre-evoked field potentials, a synaptic model of central sensitisation and hyperalgesia, ensues the application of electrical high-frequency, high-intensity conditioning stimulation to the sciatic nerve. In order to investigate the putative involvement of the G protein-coupled...
Herniation of the nucleus pulposus (NP) from lumbar intervertebral discs commonly results in radiculopathic pain and paresthesia (sciatica). While traditionally considered the result of mechanical compression of the dorsal root ganglion (DRG) and/or spinal nerve root, recent studies implicate pro-inflammatory mediators released from or evoked by NP, a possibility that was presently investigated. Single-unit...
The contribution of estrogen and progesterone to colorectal hyperalgesia was examined in female rats. The electromyogram recorded from the abdominal wall (visceromotor response, vmr) and the discharge of lumbosacral dorsal horn neurons to colorectal distention (CRD) were measured in intact female, ovariectomized (OVx) and estradiol replaced OVx (E2; 50μg, 48h) rats with and without colonic inflammation...
Patients with non-specific limb pain often show signs of nerve mechanosensitivity, i.e. local tenderness over nerve trunks and pain in response to limb movements that cause nerve stretch. In such patients a nerve lesion is not apparent, and it has been suggested that local neural inflammation may be a key factor. The present study examines the extent to which nerve fibres in regions of local inflammation...
There is compelling evidence for a strong facilitatory drive modulating spinal nociceptive transmission. This is in part via serotonergic pathways and originates from the rostroventral medulla. We previously demonstrated that neuropathic pain is associated with an enhanced descending facilitatory drive onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT acting at spinal...
Inhibitory neurotransmission in spinal cord dorsal horn is mainly mediated by γ-amino butyric acid (GABA) and glycine. By patch clamp recordings and correlative immunocytochemistry, we studied here the effect of 2μM capsaicin-induced vanilloid receptor-1 (TRPV1) activation on IPSCs in spinal lamina II neurons from post-natal mice. Specificity was confirmed after pre-incubation with the competitive...
CGRP receptor activation has been implicated in peripheral and central sensitization. The role of spinal CGRP receptors in supraspinal pain processing and higher integrated pain behavior is not known. Here we studied the effect of spinal inhibition of CGRP1 receptors on supraspinally organized vocalizations and activity of amygdala neurons. Our previous studies showed that pain-related audible and...
The proinflammatory cytokine interferon-γ (IFN-γ), which can be present in elevated levels in the central nervous system during pathological conditions, may be involved in the generation of persistent pain states by inducing neuronal hyperexcitability. The aim of the present study was to examine whether loss of dorsal horn GABAergic inhibition may underlie this IFN-γ-mediated neuronal hyperexcitability...
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