Pain
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The anterior cingulate cortex (ACC) and adjacent regions in the medial wall have been implicated in sensory, motor and cognitive processes, including pain. Our previous functional magnetic resonance imaging (fMRI) studies have demonstrated pain-related activation of the posterior portion of the ACC during transcutaneous electrical nerve stimulation (TENS) and variable patterns of cortical activation with innocuous and noxious thermal stimuli in individual subjects. The present study represents the companion paper to our recent study of pain- and thermal-related cortical activations with the aim to use fMRI to delineate the activations in the ACC and surrounding regions of the medial wall during application of innocuous and noxious thermal stimuli as well as during performance of a motor task in individual subjects. ⋯ Although the present results demonstrate intersubject variability in the task-related activations, some general modality-specific patterns were apparent: (i) innocuous thermal-related activations were located mainly in the anterior ACC; (ii) noxious thermal-related activations were primarily located in the anterior ACC, the ventral portion of the posterior ACC, and the supplementary motor area (SMA); (iii) motor-related activations were primarily located in the SMA and dorsal portion of the posterior ACC. These results indicate that specific spatial patterns of activation exist within the ACC and surrounding regions of the medial wall for innocuous and noxious thermal stimuli, and that noxious thermal- and motor-related activations appear to be segregated within the ACC. Therefore, we propose a segregation of the ACC into an anterior non-specific attention/arousal system and a posterior pain system.
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Assumptions of reliability and consistency of self-report of pain by patients using visual analogue scales (VAS) and numerical rating scales (NRS) are based on narrow considerations of possible sources of error. This study examined patients' use of VASs and NRSs, by their own description, with particular attention to rating of multiple pains, of different dimensions of pain, and of interpretation and use of lower and upper endpoints and increments on the scales. These have implications for the approximation of the scales to psychometric requirements. ⋯ Data are described with reference to lack of concordance between patients and of consistency within patients; responses suggested that ratings incorporate multiple partially differentiated dimensions of pain, with particular importance placed on function or mobility. Labels assigned to scale endpoints by researchers, whether lexical or numerical, appeared to affect their use; however, covert relabelling of scale points was revealed in free response. The action of arriving at a rating is better conceptualised as an attempt to construct meaning, influenced by and with reference to a range of internal and external factors and private meanings, rather than as a task of matching a distance or number to a discrete internal stimulus.
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An injury to a peripheral nerve in animals often leads to signs of neuropathic pain including hyperalgesia to heat, cold and mechanical stimuli. The role of injured and intact nerve fibers in mechanical hyperalgesia was evaluated in rats subjected to an L5 spinal nerve ligation-and-cut ('modified SNL lesion'). To assess the contribution of injured afferents, an L5 dorsal rhizotomy was performed immediately before, or 7 days after the modified SNL lesion. ⋯ These results suggest that, after L5 spinal nerve ligation-and-cut, mechanical hyperalgesia develops and persists independent of input from injured afferents. We propose that the Wallerian degeneration that develops after a nerve injury leads to interactions between the degenerating fibers of the injured spinal nerve and the intact fibers of adjacent spinal nerves. This leads to changes in the intact fibers that play a critical role for both initiation and maintenance of mechanical hyperalgesia.
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Musculoskeletal pain is one of the most frequent symptoms for which medical assistance is sought. Yet, the majority of our knowledge regarding pain physiology is based on studies of cutaneous tissue. Comparatively little is known about activation of visceral, joint and perhaps least of all, musculoskeletal nociceptors although clinically-treated pain originates principally in these structures. ⋯ This behavioral dependent measure is also significantly reversed by agents used clinically to treat muscle pain, indomethacin and dexamethasone, as well as the non-competitive N-methyl-D-aspartate receptor antagonist MK801. Finally, evidence that reduction in grip force is in part mediated by small, unmyelinated afferents is provided by the demonstration that neonatal capsaicin treatment significantly reduced carrageenan-evoked behavioral hyperalgesia ( approximately 45% reduction) and reduced muscle content of immunoreactive CGRP ( approximately 60% reduction) relative to control levels. Collectively, these findings provide converging lines of evidence for the validity of this animal model to investigate mechanisms involved in the development of muscle hyperalgesia.
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Comparative Study
Effects of midazolam in the spinal nerve ligation model of neuropathic pain in rats.
Potential changes in the spinal GABAergic activity after nerve injury were studied by comparing the effects of systemic administration of the benzodiazepine midazolam on the noxious evoked responses of dorsal horn in rats with spinal nerve ligation of neuropathy and control animals. The tight ligation of the L(5) and L6 spinal nerves was performed in adult male Sprague-Dawley rats and resulting mechanical and cold allodynia were assessed with von Frey hairs and the acetone drop test. Single unit extracellular recordings of dorsal horn neurones were performed 15-18 days after the surgery under halothane anaesthesia using transcutaneous electrical stimulation of the receptive field at three times the C-fibre threshold. ⋯ The inhibitory effects of s.c. midazolam were significantly reversed by i.t. administration of flumazenil, suggesting a spinal site of action. Midazolam reduced C-fibre evoked firing significantly more in the spinal nerve ligation model than in the non-operated or sham controls. These results indicate changes in the spinal GABAergic system in the neuropathic animals and could be of importance in the development of new treatments for neuropathic pain.