Articles: hyperalgesia.
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Neuroscience letters · Jan 2002
Capsaicin sensitive afferents mediate the development of heat hyperalgesia and hindpaw edema after sciatic section in rats.
Sciatic section in rats evokes chronic hyperalgesia, autotomy pain behavior, and hindpaw edema, a constellation resembling complex regional pain syndrome (CRPS) in man. Glucocorticoid treatment inhibits these sequelae of sciatic section and also blocks neurogenic extravasation. ⋯ Now, we show that pre-emptive destruction of the small diameter fibers prevents neurogenic extravasation, and prevented the development of heat hyperalgesia and hindpaw edema after sciatic section. Thus, capsaicin sensitive primary afferent neurons which release SP are required for the development of heat hyperalgesia and hindpaw edema in this animal model of CRPS.
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Activation of ERK (extracellular signal-regulated kinase) MAP (mitogen-activated protein) kinase in dorsal horn neurons of the spinal cord by peripheral noxious stimulation contributes to short-term pain hypersensitivity. We investigated ERK activation by peripheral inflammation and its involvement in regulating gene expression in the spinal cord and in contributing to inflammatory pain hypersensitivity. Injection of complete Freund's adjuvant (CFA) into a hindpaw produced a persistent inflammation and a sustained ERK activation in neurons in the superficial layers (laminae I-IIo) of the dorsal horn. ⋯ CFA-induced phospho-ERK primarily colocalized with prodynorphin and NK-1 in superficial dorsal horn neurons. Although intrathecal injection of U0126 did not affect basal pain sensitivity, it did attenuate both the establishment and maintenance of persistent inflammatory heat and mechanical hypersensitivity. Activation of the ERK pathway in a subset of nociceptive spinal neurons contributes, therefore, to persistent pain hypersensitivity, possibly via transcriptional regulation of genes, such as prodynorphin and NK-1.
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Neuropathic pain represents a series of relatively uncommon chronic pain conditions, caused by lesions or dysfunctions of peripheral or central afferent pathways in the nervous system. The symptoms and signs of neuropathic pain can all be explained by a neuronal hyperexcitability at the site of the nerve lesion, which subsequently and in a dynamic fashion recruits more central sites. The manifestations of such neuronal hyperexcitability are therefore rather similar, irrespective of the causes or sites of the lesions. ⋯ Our understanding of the mechanisms underlying neuronal hyperexcitability has increased dramatically within the last decade, and accordingly, it has been suggested that pain be classified according to a mechanism-based approach. The challenge for an improved understanding of neuropathic pain--which is the key for better treatment--lies in elucidating the relationships between symptoms, signs, aetiology, anatomical lesions, and underlying mechanisms. At present, this is not a trivial task.
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While it may be convenient to categorize neuropathic pain syndromes on the basis of anatomical distribution or disease state (e.g., diabetic neuropathy, radiculopathy, postherpetic neuralgia), the treatment of neuropathic pain, alone, should also consider the signs and symptoms and the underlying putative mechanisms that may then be inferred from each individual's signs and symptoms. A diagnosis-based approach to treatment may not effectively relieve a patient's pain or improve his or her quality of life, the ultimate goal of treatment. Although research that supports a symptom- and mechanism-based approach to treating neuropathic pain is ongoing and dynamic, the preclinical and clinical data available thus far form an initial rational framework within which we may attempt to target putative pain mechanisms.
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Secondary hyperalgesia, an exaggerated response to stimuli applied to undamaged tissue surrounding an injury, is a common consequence of tissue injury and inflammation. It is well established that the etiology of secondary hyperalgesia is sensitization of central neurons but the exact mechanism and its role in certain clinical pain states is unclear. In the present experiments, we studied responses to punctate and non-punctate mechanical stimuli and to heat applied to the plantar aspect of the hindpaw remote to an incision in the gastrocnemius region of the rat hindlimb. ⋯ Reduced withdrawal thresholds were blocked by i.t. administration of morphine and by local anesthetic injection at the test site 2h and 2 days after gastrocnemius incision. These pharmacological data provide evidence that reduced withdrawal thresholds after gastrocnemius incision are nociceptive behaviors indicating persistent secondary hyperalgesia. Because the behaviors have a similar time course to secondary hyperalgesia in postoperative patients, the model will be useful to evaluate the mechanisms for secondary mechanical hyperalgesia after incision, its pharmacological characteristics and its potential role in persistent postoperative pain.