Pain
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We have addressed the role of the sympathetic nervous system in the development and maintenance of neuropathic pain. Using a new neuropathic mouse model, we examined the development of hyperalgesia in transgenic mice lacking functional alpha(2A) adrenoceptors and in sympathectomized wild-type mice, to determine if sympathetic-sensory coupling generates hyperalgesia. The development of neuropathic heat hyperalgesia required the presence of both the alpha(2A) adrenoceptor and the sympathetic postganglionic neuron (SPGN), but the development of mechanical hyperalgesia did not require either the alpha(2A) adrenoceptor or the SPGN, indicating different mechanisms of sensitization. ⋯ The peripherally restricted alpha(2) antagonist L659,066 evoked analgesia for heat, but not for mechanical stimuli, findings which support the hypothesis that the peripheral alpha(2) adrenoceptor plays a role in both the development and the maintenance of neuropathic heat hyperalgesia. The alpha(2) antagonist-evoked analgesia for heat stimuli was mediated by blocking peripheral and probably central alpha(2) adrenoceptors, while the analgesia for mechanical stimuli was mediated by blocking central alpha(2A) adrenoceptors. Intradermal injections with an alpha(2) agonist or antagonist had no effect on nociceptive thresholds, indicating that sympathetic-sensory coupling at the level of the cutaneous nociceptor did not contribute to the maintenance of neuropathic hyperalgesia.
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We examined the relation between ectopic afferent firing and tactile allodynia in the Chung model of neuropathic pain. Transection of the L5 spinal nerve in rats triggered a sharp, four- to six-fold increase in the spontaneous ectopic discharge recorded in vivo in sensory axons in the ipsilateral L5 dorsal root (DR). The increase, which was not yet apparent 16 h postoperatively, was complete by 24 h. ⋯ Axotomy triggers a wide variety of changes in the neurochemistry and physiology of primary afferent neurons. Investigators studying DRG neurons in culture need to be alert to the rapidity with which axotomy, an inevitable consequence of DRG excision and dissociation, alters key properties of these neurons. Our identification of a specific population of neurons whose firing properties change suddenly and synchronously following axotomy, and whose activity is associated with tactile allodynia, provides a powerful vehicle for defining the specific cascade of cellular and molecular events that underlie neuropathic pain.
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Randomized Controlled Trial Clinical Trial
Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients.
Central mechanisms related to referred muscle pain and temporal summation of muscular nociceptive activity are facilitated in fibromyalgia syndrome (FMS) patients. The present study assessed the effects of an NMDA-antagonist (ketamine) on these central mechanisms. FMS patients received either i.v. placebo or ketamine (0.3 mg/kg, Ketalar((R))50% decrease in pain intensity at rest by active drug on two consecutive VAS assessments). ⋯ The present study showed that mechanisms involved in referred pain, temporal summation, muscular hyperalgesia, and muscle pain at rest were attenuated by the NMDA-antagonist in FMS patients. It suggested a link between central hyperexcitability and the mechanisms for facilitated referred pain and temporal summation in a sub-group of the fibromyalgia syndrome patients. Whether this is specific for FMS patients or a general phenomena in painful musculoskeletal disorders is not known.
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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.