Contribution of afferent pathways to nerve injury-induced spontaneous pain and evoked hypersensitivity.
ABSTRACT A predominant complaint in patients with neuropathic pain is spontaneous pain, often described as burning. Recent studies have demonstrated that negative reinforcement can be used to unmask spontaneous neuropathic pain, allowing for mechanistic investigations. Here, ascending pathways that might contribute to evoked and spontaneous components of an experimental neuropathic pain model were explored. Desensitization of TRPV1-positive fibers with systemic resiniferatoxin (RTX) abolished spinal nerve ligation (SNL) injury-induced thermal hypersensitivity and spontaneous pain, but had no effect on tactile hypersensitivity. Ablation of spinal NK-1 receptor-expressing neurons blocked SNL-induced thermal and tactile hypersensitivity as well as spontaneous pain. After nerve injury, upregulation of neuropeptide Y (NPY) is observed almost exclusively in large-diameter fibers, and inactivation of the brainstem target of these fibers in the nucleus gracilis prevents tactile but not thermal hypersensitivity. Blockade of NPY signaling within the nucleus gracilis failed to block SNL-induced spontaneous pain or thermal hyperalgesia while fully reversing tactile hypersensitivity. Moreover, microinjection of NPY into nucleus gracilis produced robust tactile hypersensitivity, but failed to induce conditioned place aversion. These data suggest that spontaneous neuropathic pain and thermal hyperalgesia are mediated by TRPV1-positive fibers and spinal NK-1-positive ascending projections. In contrast, the large-diameter dorsal column projection can mediate nerve injury-induced tactile hypersensitivity, but does not contribute to spontaneous pain. Because inhibition of tactile hypersensitivity can be achieved either by spinal manipulations or by inactivation of signaling within the nucleus gracilis, the enhanced paw withdrawal response evoked by tactile stimulation does not necessarily reflect allodynia.
British Journal of Radiology 02/1992; 65(769):94. · 1.31 Impact Factor
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ABSTRACT: The influence of sensory symptoms on overall simple pain ratings in neuropathic pain is not well understood. The goal of this study was to determine this relationship by using the Neuropathic Pain Questionnaire (NPQ) and Neuropathic Pain Scale (NPS) in patients who had neuropathic pain. Overall pain intensity ratings were assessed by means of Average and Worst Pain ratings from the Brief Pain Inventory. Ongoing average pain was rated as 5.7 and worst pain as 7.7 on 0 to 10 scale, and it was present in 96% of patients, whereas symptoms that are commonly studied in the laboratory, such as increased pain due to touch and due to heat, were much less frequent (64% and 38%, respectively). Worst pain was most highly correlated with shooting, stabbing, and distress symptom complex, which was in contrast to Average pain, which was most highly correlated with symptom complex consisting of a large number of items. Analysis of conceptually related thermal heat sensation types of pain, spontaneous "burning" pain and the evoked pain "increased due to heat," showed that spontaneous burning pain was reported at much higher frequency and intensity than the evoked increased pain due to heat. There was no statistically significant difference between descriptors from NPS and NPQ among subgroups of neuropathic pain, such as polyneuropathy, radiculopathy, or posttraumatic neuralgia, but this could be in part due to relatively small number of patients in these subgroups of neuropathic pain. Quantitative analysis, as performed in this study, is one of the steps in developing an approach for elucidating the relationship between neuropathic pain symptoms and underlying mechanisms. PERSPECTIVE: Assessment of neuropathic pain symptoms by means of specifically designed questionnaires provides significant insight into patients' pain experience, including pain overall, which is under many influences. Further research of this type can contribute to advances in mechanism-based diagnosis and treatment.Journal of Pain 12/2004; 5(9):491-7. · 4.93 Impact Factor
Article: Mechanisms of neuropathic pain.[show abstract] [hide abstract]
ABSTRACT: Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, "channelopathies," and autoimmune disease are examples of diseases that may cause neuropathic pain. The development of both animal models and newer pharmacological strategies has led to an explosion of interest in the underlying mechanisms. Neuropathic pain reflects both peripheral and central sensitization mechanisms. Abnormal signals arise not only from injured axons but also from the intact nociceptors that share the innervation territory of the injured nerve. This review focuses on how both human studies and animal models are helping to elucidate the mechanisms underlying these surprisingly common disorders. The rapid gain in knowledge about abnormal signaling promises breakthroughs in the treatment of these often debilitating disorders.Neuron 11/2006; 52(1):77-92. · 14.74 Impact Factor